Genetic variants associated with disordered eating

Genetic variants associated with disordered eating

Tracey D Wade, PhD1, Scott Gordon, PhD2, Sarah Medland, PhD2, Cynthia M. Bulik, PhD3,4,Andrew C Heath, DPhil5, Grant W Montgomery, PhD2, and Nicholas G Martin, PhD2

1School of Psychology, Flinders University, Adelaide, Australia2Queensland Institute of MedicalResearch, Brisbane, Australia3Department of Psychiatry, University of North Carolina, Chapel Hill, USA4Department of Nutrition, University of North Carolina, Chapel Hill, USA5Department of Psychiatry, Washington University, St Louis, USA

AbstractObjective—While the genetic contribution to the development of anorexia nervosa (AN) haslong been recognized, there has been little progress relative to other psychiatric disorders inidentifying specific susceptibility genes. Here we have carried out a GWAS on an unselectedcommunity sample of female twins surveyed for eating disorders.

Method—We conducted genome wide association analyses in 2564 female twins for fourdifferent phenotypes derived from self-report data relating to lifetime presence of 15 types ofdisordered eating: anorexia nervosa spectrum, bulimia nervosa spectrum, purging via substances,and a binary measure of no disordered eating behaviors versus 3 or more. To complement thevariant level results we also conducted gene-based association tests using VEGAS.

Results—While no variants reached genome-wide significance at the level of p<10−8, sixregions were suggestive (p<5×10−7). The current results implicate the following genes: CLEC5A;LOC136242, TSHZ1 and SYTL5 for the anorexia nervosa spectrum phenotype, NT5C1B for thebulimia nervosa spectrum phenotype, and ATP8A2 for the disordered eating behaviors phenotype.

Discussion—As with other medical and psychiatric phenotypes, much larger samples and meta-analyses will ultimately be needed to identify genes and pathways contributing to predisposition toeating disorders.

Twin studies suggest that around 60% of the variance in risk for developing anorexianervosa (AN) and disordered eating is due to genetic factors,1–3 with more variableestimates attributed to bulimia nervosa (BN, ranging from 28%4 to 83%5). Linkage studiesidentified regions on chromosomes 1, 2, 4, and 13 as suggestive of linkage for AN6,7 withfollow-up significant association of the delta opioid receptor (OPRD1) and serotonin (5-HT)receptor 1D (HTR1D) genes, both on Chromosome 1.8 For BN, significant linkage wasobserved on chromosome 10 and another region on chromosome 14 was suggestive forgenome-wide linkage.9 Well over 200 candidate gene association studies of eating disordershave been conducted, focusing primarily, but not exclusively on serotonergic, dopaminergic,and appetite regulatory genes; however, due largely to an overreliance on small samples,replication has not been universal and clear conclusions remain elusive.10

Author to whom correspondence should be sent: Professor Tracey Wade, School of Psychology, Flinders University, GPO Box 2100,Adelaide, SA, Australia, 5001. [email protected]; phone: +61-8-8201-3736; fax: +61-8-8201-3877.

Disclosure of conflictsAll authors report no biomedical financial interest or potential conflicts of interest.

NIH Public AccessAuthor ManuscriptInt J Eat Disord. Author manuscript; available in PMC 2014 September 01.

Published in final edited form as:Int J Eat Disord. 2013 September ; 46(6): 594–608. doi:10.1002/eat.22133.

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The current preferred approach to rectifying the nebulous results emerging from a litany ofunderpowered studies is to boost power throughmeta-analyses of multiple Genome WideAssociation Studies (GWAS). In contrast to candidate gene association studies that focus onpre-specified genes of interest, GWAS represent an unbiased scan of the entire genome forcommon genetic variation in cases versus healthy controls. To date threeGWASinvestigations11–13 have been published for eating disorders, none of which have yieldedgenome-wide significant single-nucleotide polymorphisms (SNPs), where adequatesignificance is set at P<10−8, as suggested by Li et al14. The first, from the Japanese GeneticResearch Group for Eating Disorders,11 showed the strongest associations for AN in 320cases and 341 controls at 1q41 (with the most significant association observed at SNPrs2048332) and 11q22 (associated with 4 SNP markers, rs6590474, D11S0268i, rs737582,rs7947224). The second study of 1033 AN cases and 3733 pediatric controls12 hadtopassociation signals detected near ZNF804B, CSRP2BP, NTNG1, AKAP6 and CDH9. Thislatter gene codes for a neuronal cell-adhesion proteins that influences how neuronscommunicate with each other in the brain and has been associated with autism spectrumdisorders. The third study13 which examined six eating disorder-related symptoms,behaviours and personality traits in 2,698 individuals detected association of eight geneticvariants with P<10−5, and an associated meta-analysis showing five SNP markers (andassociated genes) met genome-wide significance level:rs6894268 (RUFY1), rs7624327(CCNL1), rs10519201 (SHC4), rs4853643 (SDPR), rs218361 (TRPS1). A further GWAS ofAN, conducted by the International Wellcome Trust Case Control Consortium (WTCCC3)on 2,907 patients with AN and 14,860 geographically matched controls, is in progress.15

Eating disorders are associated with the highest mortality of any psychiatric disorder.16–19

Best evidence treatment approaches have been identified for bulimic disorders20 buttheevidence base for how best to treat AN is weak.21 There are no medications that arecurrently considered to be effective in the treatment of AN and progress in this area has beenhampered by a lack of knowledge about the underlying neurobiology of the condition. Theclear-cut identification of genomic variation that predisposes to eating disorders can providethe basis for the next generation of research into etiology, treatment, and prevention.

In line with evidence that shows that large-scale collaborative GWAS studies and largersample sizes can achieve the necessary power to identify specific loci in psychiatricdisorders,22,23 the aim of this study is to contribute to the accumulation of a larger samplesize related to disordered eating. The current study conducted a GWAS of four differentphenotypes of disordered eating in an unselected sample of 2564 female twins in order tofurther our knowledge of the genomic variation that predisposes to core features of eatingdisorders. This represents only the fourth published GWAS in eating disorders, and so asecondary aim was to see whether we could achieve any replication with thepreviouspublished studies11–13.

Materials and methodsParticipants

Participants were from the volunteer adult Australian Twin Registry (ATR) maintained bythe National Health and Medical Research Council. These data are from two cohorts ofwomen who completed a mailed questionnaire survey 1988–92, as shown in Figure 1. Thefirst cohort, born before 1964, hasbeen previously described,3,24,25 and an examination oftheir socio-demographic features, including age, marital status, educational background,workforce participation, major lifetime occupation, and religious denomination, suggeststhat the sample is not notably different from the Australian female population (using dataobtained from the Australian Bureau of Statistics between 1986 and 1992). The secondcohort included women born between 1964 and 1971 and has also been previously

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described.26,27 Most of these twins had been recruited when at school some ten years earlier.All applicable institutional regulations concerning the ethical use of human volunteers werefollowed during this research. The final combined sample where there were both phenotypicdata for disordered eating and genotypes comprised 2564 women.

PhenotypesThe 1988–92 surveys mailed to female twins contained five questions assessing disorderedeating and these are shown in Table 1. These questions produced a total of 15 variablesrelating to disordered eating. A previous examination of these items along with twosubsequent measures of eating disordered behavior indicated that 60% (95% CI: 50–68) ofthe variance could be attributed to additive genetic influences.3 In the younger cohort, afollow-up telephone interview was conducted in 2001–2003 when they were aged 28 to 40years of age (about 10 years after the self-report questionnaire) using the Eating DisorderExamination (EDE28) with 1,083 women, indicating a moderate association (r=0.31 and0.38 for Twin 1 and 2 respectively) between the mean number of 16 possible problemsendorsed in the self-report questionnaire and total number of 6 possible eating disorderbehaviors endorsed at interview.27 Moderate agreement is also obtained between twodifferent interview schedules (including the EDE) assessing eating disorders18–24 monthsapart, achieving a kappa less than 0.60.29

As shown in Figure 1, four different phenotypes relating to disordered eating wereexamined. The first three phenotypes were derived from an exploratory factor analysis of the15 variables for all available data, whether women had been genotyped or not. The resultantfactors are shown in Table 1, where items with factor loadings ≥ 0.2 are highlighted. Ofinterest to the current investigation were those factors that related to disordered eating,namely Factor 1 (anorexia nervosa spectrum), Factor 2 (bulimia nervosa spectrum) andFactor 3 (purging via substances).

For the fourth phenotype (disordered eating behaviors), the item relating to “difficultycontrolling weight” was excluded as it was endorsed so widely that it was considered not tobe indicative of disordered eating but rather of the normative struggle many women feel thatthey have with their weight. The remaining 14 items were reduced to a binary variable,where women who endorsed “no” for all items were grouped as “controls”, and women whoendorsed 3 or more problems were grouped as “cases”.

GenotypingGenotypes were drawn from an existing QIMR Genetic EpidemiologyLaboratory GWASdata for >19,000 individuals (comprised of twin pairs, nuclear families, or singletons),which integrates data from eight batches of genotyping obtained using standard Illuminachips. The subset used here includes individuals typed withthe 610K-quad chip(1138individuals); 370K or 370K-duo chips (738 individuals); or the Illumina 317K chip (644individuals); 316 individuals were genotyped on more than one chip either for deliberate QCreasons or to obtain highercoverage than an early generation chip used previously.Individual genotypes were eliminated where they conflict between monozygotic twins orrepeat genotypings, as well as (within each family) all genotypes for markers withMendelian errors. All twin-family members were used in the genetic analysis, takingaccount of their relatedness (see below).

Within each batch, genotypes were called using the Genotyping Module in Beadstudio andthen exported. Cleaning was later performed (a) per-SNP to remove SNPs with (1) MAF<1%; (2) call rate <95%; (3) mean GenCall score <0.7; or (4) Hardy-Weinberg p-value<10−6; and (b) per-individual to remove individuals with (in their batch) a call rate <95% or

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other obvious quality issues; or (c) in the integrated dataset, having (1) an unresolvablesample mix-up, zygosity or pedigree issue after archival investigation of outlier familiesfrom IBS and IBD-based relatedness checks; or (2) being an ancestry outlier based on lying>6sd from the PC1 or PC2 mean for Europeans in a Principal Components Analysis run inSMARTPCA v3, with all HapMap Phase II/III and non-QIMR EUTWIN populations usedas a training set. The dataset contains verified pedigree data for all individuals barring asmall number of distant relationships (typical π-hat<0.1).

Measured genotypes for the ~281,000 SNPs passing QC in all genotyping batcheswere usedto impute to 1000 Genomes SNPs (Release 20100804) via the recommended pre-phasingmethod in MACH and Minimac30, using the publicly available EUR phased haplotypes asreference panel (from the formatted 1000 Genomes haplotype files supplied by the softwareauthors’ web site, for this purpose). In all, 7262007 SNPs were initially analysed (this isafter the R2 quality control test but not the MAF test), and 6150213 SNPs remained afterfiltering out those with MAF (Minor Allele Frequency) < 2%. Since people genotypedalready had their zygosity assessed previously in various ways, no twin pairs needed to bediscarded due to discordance revealed by genotyping. The number of twins passing qualitycontrol varied by phenotype: 2524 for the anorexia nervosa spectrum, 2442 for the bulimianervosa spectrum, 2521 for purging via substances, 1659 for the 14-item disordered eatingscore.

Statistical analysisFour case/control phenotypes were analyzed. To allow for both developmental and secularcohort effects on these phenotypes we included age, age2, cohort, age*cohort, age2*cohortas covariates. Analyses were conducted using MERLIN-OFFLINE, which implements atotal test of association using allele dosage scores while explicitly modeling the relationshipstructure within our MZ and DZ twin families.31 Variants with poor imputation accuracy(R2<0.3) and rare variants (MAF<0.02) were excluded from analyses.

Gene-based association tests were run on the association results for common variantsusingVEGAS32(v0.8.27). Note that VEGAS as currently configured identifies SNPs within genesbased on the geneboundaries as defined by Build 36 (hg18) coordinates, and returns resultsin these coordinates. VEGAS results reported here have been converted to Build 37 (hg19)for consistency with other quoted positions. Due to software limitations, only SNPs found inHapMap II genotypes were analyzed, and results for the X chromosome are not availablefrom VEGAS.

ResultsGenome-wide association of SNP data

The results of the GWAS analyses for each of our four binary eating disorder variables aresummarized in the Manhattan plots presented in Figure 2. LD pruned results for variantsp<10−5are provided in Table 2. The top 100 gene-based results from VEGAS are listed inTable 3.

Many of those with one (or few) associated SNPs per peak appear to represent false positivesignals, as either they are not in LD with adjoining SNPs, or are in LD but adjoining SNPsare not also associated. Peaks shown with ≤2 SNPs in Table 2 were all manually inspectedto ascertain if they contained a signal off the listed SNP(s). In the majority of instances thereis no association signal off the listed SNP(s) even without applying the ‘MAF≥2%’ filter toassociation results. In others there are other mildly associated SNPs with no signal inbetween. The most notable such exceptions have been footnoted in Table 2.

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The initial GWAS analyses yielded a number of suggestive association signals,althoughnone reached genome-wide significance for common variants within1KGP imputeddata of p<10−8. Regional association plots for the sesuggestive signals are shown in Figure3. The power associated with our strongest SNPs (at p<10−5) was R2<0.5 for 9, R2<0.6 for15, and R2<0.7 for 21, indicating that they were well imputed.

Attempted replication of results from the previous GWAS studiesWe examined our results for the regions containing SNPs and CNV regions reported asassociated with AN by Wang et al,12 and the other previously-reported associated SNPsreported earlier13,33 and in a Japanese population,11 replication of which was tested in Wanget al. The p-values for the relevant SNPs in our data are reported in Table 4, along withMAF from our imputed data and the referenced papers (all for Europeans for Wang et al12;for Japanese by Nakabayashi et al11) for rs2048332. Our frequencies are consistent with therange between case and control frequencies for Wang et al12 (suggesting good imputation)but we fail to replicate (in any of our phenotypes)their associated SNPs for AN, or thosereported earlier.11,13,33 We do find a nominally significant association (p~0.01) in both theBN spectrum and 14-item disordered eating behavior variable for rs906281, which Wang etal12 investigated as a proxy for rs2048332 which was itself reported by Nakabayashi et al.11

However this is significant only in terms of the limited number of tests shown in Table 5,and is for a different population.

DiscussionThe current study represents only the fourth published GWAS for eating disorders-relatedphenotypes and extends the literature by examining four broad eating disorder phenotypesassessed by self-report - anorexia nervosa spectrum, bulimia nervosa spectrum, purging viasubstances, and disordered eating behaviors. A number of suggestive signals were identified,although none reached genome-wide significance at the level of p<10−8. The strongestevidence of association was observed at rs145241704, rs62090893 and rs56156506 for theanorexia nervosa spectrum phenotype, rs1445130 for the bulimia nervosa spectrumphenotype, rs138206701 for the purging phenotype, and rs7322916 for the disordered eatingbehaviors phenotype.

The strongest signal for our anorexia nervosa spectrum variable is located in a gene richregion on chromosome 7 (141.5Mb). Within this region are a number of promisingpositional candidates. The peak variant in this region, rs145241704, is located within themRNA DQ571874 which has previously been identified as a Piwi-interacting RNA playinga role in gamete development. However, the LD block within this region includes a numberof taste receptor genes including TAS2R3, TAS2R4 and TAS2R5, which encode bitter tastereceptors. Such receptors have previously been shown to influence perception and eatingbehaviors with respect to certain foods. Also within this region is CLEC5A, which is acarbohydrate-binding protein domain which has a diverse range of functions including cell-cell adhesion, immune response to pathogens and apoptosis. The next strongest signal,which peaked at rs62090893encompasses theTSHZ1gene. Notably, in a recent studyexamine changes in gene expression in response to bariatric surgery in a sample of patientswith Type 2 diabetes34, changes in expression of TSHZ1 were correlated with changes inweight, fasting plasma glucose and glycosylated hemoglobin.

The strongest result for the for the BN spectrum phenotype, was located in an intergenicregion centered around rs1445130 on chromosome 2. Recent results from the ENCODEconsortium have shown enrichment of the H3K27Ac histone marks within this regionsuggesting that there may be an active regulatory region nearby. The closest gene, NT5C1B,

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plays a role in the production of adenosine, which plays an important role in biochemicalprocesses, such as energy transfer.

Consistent with research in other areas of psychiatric genetics prior to accumulation of largesample sizes, there was no meaningful replication between previous genome-wide studies ofAN and our current results. If eating disorders follows the same scientific trajectory of othermedical and psychiatric disorders, which is increased replication and clarity withincreasingly large sample sizes35 - and there are not theoretical reasons why they should not- then we would expect more concrete results as we combine samples into meta-analyses.

The current study has a number of limitations; first, we used self-report data that are notdirectly reflective of the diagnostic criteria for eating disorders. While our data cluster inrecognizable eating disorder syndromes,25 the phenotypes represent rather a bluntinstrument for identifying specific eating disorders. Second, as with other studies ofpsychiatric illness that have used population based samples, the analyses are underpowered.Third, there are there are only 45persons who would qualify for a diagnosis of BN or AN inour genotypedsample,36 so our ability to contribute cases to larger case-control samples islimited. However, GWAS now exist that are not focused on diagnosis but on eatingdisorder-related symptoms and behaviors.13 As GWAS meta-analysis by definition requiresthe availability of a number of samples, and a review of the genetic architecture ofpsychiatric disorders shows that sample size is of greater importance than heritability withrespect to the identification of specific loci,22 our analyses should make a usefulcontribution towards improving the power to identify genetic variants influencing symptomsand behaviours related to eating disorders through the conduct of meta- and mega-analyseswith other such GWAS.

AcknowledgmentsSupported by National Institutes of Health Grants AA07535, AA07728, AA13320, AA13321, AA14041,AA11998, AA17688, DA012854, and DA019951; by Grants from the Australian National Health and MedicalResearch Council (241944, 339462, 389927,389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485,and 552498); and by the 5th Framework Programme (FP-5) GenomEUtwin Project (QLG2-CT-2002-01254).Genome-wide association study genotyping at Center for Inherited Disease Research was supported by a Grant tothe late Richard Todd, M.D., Ph.D., former Principal Investigator of Grant AA13320. SEM and GWM aresupported by the National Health and Medical Research Council Fellowship Scheme. We also thank Dixie Stathamand Anjali Henders (phenotype collection); Lisa Bowdler and Steven Crooks (DNA processing); and David Smyth(Information Technology support) at Queensland Institute of Medical Research, Brisbane Australia. Last, but notleast, we thank the twins and their families for their participation.

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3. Wade TD, Martin NG, Neale MC, Tiggemann M, Treloar SA, Bucholz K, et al. The structure ofgenetic and environmental risk factors for three measures of disordered eating. Psychological Med.1999; 29:925–934.

4. Kendler KS, Walters EE, Neale MC, Kessler RC, Heath AC, Eaves LJ. The structure of the geneticand environmental risk factors for six major psychiatric disorders in women: Phobia, generalizedanxiety disorder, panic disorder, bulimia, major depression, and alcoholism. Arch Gen Psychiatry.1995; 52:374–383. [PubMed: 7726718]

5. Bulik CM, Sullivan PF, Kendler KS. Heritability of binge-eating and broadly defined bulimianervosa. Biol Psychiatry. 1998; 44:1210–1218. [PubMed: 9861464]

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6. Grice DE, Halmi KA, Fichter MM, Strober M, Woodside DB, Treasure JT, et al. Evidence for asusceptibility gene for restricting anorexia nervosa on Chromosome 1. Am J Hum Genet. 2002;70:787–792. [PubMed: 11799475]

7. Devlin B, Klump KL, Bacanu SA, Bulik CM, Strober M, Berrettini W, et al. Linkage analysis ofanorexia nervosa incorporating behavioral covariates. Human Mol Genet. 2002; 11:689–696.[PubMed: 11912184]

8. Bergen AW, van den Bree MB, Yeager M, Welch R, Ganjei JK, Haque K, et al. Candidate genes foranorexia nervosa in the 1p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibitsignificant association to anorexia nervosa. Mol Psychiatry. 2003; 8:397–406. [PubMed: 12740597]

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10. Trace SE, Baker JH, Peñas-Lledó E, Bulik CM. The genetics of eating disorders. submitted.

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28. Fairburn, CG.; Cooper, Z. The eating disorder examination. In: Fairburn, CG.; Wilson, GT.,editors. Binge Eating: Nature, Assessment and Treatment. 12. NY: Guilford Press; 1993. p.317-360.

29. Wade TD, Tiggemann M, Martin NG, Heath AC. A comparison of the Eating DisorderExamination and a general psychiatric interview. Aust NZ J Psychiatry. 1997; 31:852–857.

30. Howie B, Fuchsberger C, Stephens M, Marchini J, Abecasis GR. Fast and accurate genotypeimputation in genome-wide association studies through pre-phasing. Nat Genetics. 2012; 44:955–959. [PubMed: 22820512]

31. Abecasis GR, Cherny SS. Merlin-rapid analysis of dense genetic maps using sparse gene flowtrees. Nat Genet. 2002; 30:97–101. [PubMed: 11731797]

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33. Brown KM, Bujac SR, Mann ET, Campbell DA, Stubbins MJ, Blundell JE. Further evidence ofassociation of OPRD1 & HTR1D polymorphisms with susceptibility to anorexia nervosa. BiolPsychiatry. 2007; 61:367–373. [PubMed: 16806108]

34. Berisha SZ, Serre D, Schauer P, Kaskyap SR, Smith JD. Changes in whole blood gene expressionin obese subjects with type 2 diabetes following bariatric surgery: a pilot study. PLoS One. 2011;6:e16729. [PubMed: 21423737]

35. Sullivan PF, Daly MJ, O’Donovan M. Genetic architectures of psychiatric disorders: the emergingpicture and its implications. Nat Rev Genet. 2012; 13(8):537–51. [PubMed: 22777127]

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Figure 1.Flow diagram depicting sample and data used in the GWAS

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Figure 2.Manhattan plots: 1000 Genomes-based dosage scores (SNPs with R2>0.3& MAF>0.02) forthe four disordered eating phenotypes analysed. Vertical scale is −log10(p); p<10−8 isconsidered significant. Horizontal scale is hg19/Build 37 position. Green for SNPs withp<10−5, otherwise alternate colours for alternate chromosomes.

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Figure 3.Association peak regional plots of per-SNP association p-values for (1) the most highlyassociated but plausible association peaks for each phenotype (i.e. containing a group ofadjoining associated SNPs in high LD);(2) additional associated genes (highlighted in boldin Tables 3 and 4). Obtained for Build 37/hg19 coordinates using v1.1 of LocusZoom, withLD data for 1000 Genomes release 20101123 (http://genome.sph.umich.edu/wiki/LocusZoom_Standalone). Shown with recombination rate (underlying blue graph) andannotated with names and positions of known genes if any (box below each plot). Symbolsfor SNPs are: filled diamond for most associated SNP (as named); filled triangle ifgenotyped or open triangle if purely imputed. Colouring indicates LD with the named SNP(grey = LD unknown) based on genotypes from 1000 Genomes release ‘20101123’. Thephenotype name is labeled below each panel.

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http://genome.sph.umich.edu/wiki/LocusZoom_Standalone

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Tabl

e 1

End

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men

t of

15 s

elf-

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item

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ampl

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of th

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able

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are

in b

old

Item

>1 it

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nsw

ered

(%, N

=610

4)G

enot

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ales

(%, N

=256

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rolli

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132

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138

0.37

5

Do

you

feel

you

hav

e be

en p

reoc

cupi

edw

ith th

ough

ts o

f fo

od o

r bo

dy w

eigh

t?36

.937

.1−

0.04

−0.

051

−0.

111

0.40

2

Hav

e yo

u ev

er u

sed

any

of th

e fo

llow

ing

met

hods

to c

ontr

ol y

our

body

wei

ght?

Star

vatio

n12

.411

.90.

055

0.02

70.

172

0.07

6

Exc

essi

ve e

xerc

ise

13.6

12.6

0.01

50

0.06

80.

164

Lax

ativ

es7.

77.

80.

013

−0.

022

0.46

1−

0.12

5

Flui

d ta

blet

s7.

47.

6−

0.01

6−

0.08

0.50

6−

0.16

3

Slim

min

g ta

blet

s16

.317

.4−

0.06

7−

0.06

40.

324

0.05

9

Self

-ind

uced

vom

iting

4.5

3.8

−0.

041

0.28

0.20

7−

0.08

7

Hav

e yo

u ev

er s

uffe

red

from

or

been

trea

ted

for:

Bin

ge e

atin

g2.

62.

9−

0.08

40.

455

−0.

139

0.02

7

Bul

imia

1.0

0.9

−0.

105

0.52

5−

0.03

2−

0.10

2

Eat

ing

diso

rder

3.5

3.3

0.20

80.

156

−0.

090.

014

Ano

rexi

a ne

rvos

a1.

81.

70.

301

0.02

30.

014

−0.

067

Low

bod

y w

eigh

t5.

05.

10.

426

−0.

148

−0.

017

−0.

052

Wei

ght l

oss

5.9

5.8

0.39

4−

0.15

80.

003

−0.

011


NIH


NIH


NIH


Wade et al.

Tabl

e 2

Sing

le-S

NP

Ass

ocia

tion

Peak

s fo

r in

divi

dual

100

0 G

enom

es S

NPs

- p

eaks

hig

hlig

hted

in b

old

are

plot

ted

in F

igur

e 3

Chr

Star

t (b

p,B

uild

37)

End

(bp

, Bui

ld37

)#

SNP

s (p

<10−5

)SN

P w

ith

low

est

plo

wes

t p-

val

ueE

ffec

t al

lele

Oth

er a

llele

Eff

ect

=Bet

aSE

Impu

tati

on R

2

Impu

ted

Alle

le f

req

(%)

Gen

es a

t th

ese

SNP

sG

enes

wit

hin

(app

rox)

+/−

50k

b

Ano

rexi

a ne

rvos

a sy

ndro

me

fact

or c

ase/

cont

rol

714

1450

588

1416

6581

1065

rs14

5241

704

1.51

E-0

7T

G−0

.143

0.02

70.

542

95.2

CL

EC

5A;

LO

C13

6242

KIA

A11

47;

MG

AM

; O

R9A

4;SS

BP

1; T

AS2

R3;

TA

S2R

4;T

AS2

R5;

TA

S2R

38;

WE

E2

1872

9864

9573

0727

7926

rs62

0908

932.

84E

-07

GA

−0.0

850.

017

0.87

692

.1T

SHZ

1C

18or

f62

X37

9056

4238

0093

5255

rs56

1565

069.

51E

-07

AT

−0.0

530.

011

0.99

481

.3SY

TL

5

1087

6929

6587

6942

922

rs76

7659

682.

21E

-06

TC

−0.

064

0.01

40.

716

85.6

GR

ID1

1077

2986

091

rs20

4309

03.

26E

-06

AG

−0.

119

0.02

60.

727

95.9

594

1485

381

rs46

9339

3.45

E-0

6A

G−

0.14

40.

031

0.87

597

.7M

CT

P1

712

1934

321

rs11

4945

094

3.60

E-0

6G

A−

0.13

50.

029

0.46

495

.9

887

8742

9296

5044

723

rs77

7420

183.

83E

-06

AG

−0.

117

0.02

50.

609

94.6

CN

BD

1

179

2189

4079

2279

567

rs19

3702

04.

45E

-06

TC

−0.

041

0.00

91.

000

68.1

1012

7025

691

rs75

2631

406.

44E

-06

AG

−0.

172

0.03

80.

435

97.4

CA

MK

1D

1679

1847

5379

1868

862

rs80

5018

76.

57E

-06

TC

−0.

044

0.01

00.

939

73.6

WW

OX

222

3353

446

1rs

1749

6827

7.29

E-0

6C

A−

0.04

20.

009

0.76

755

.0SG

PP2

118

0128

044

1801

3072

32

rs55

9469

078.

54E

-06

CT

−0.

066

0.01

50.

888

90.1

QSO

X1

CE

P350

1385

5482

0785

5497

362

rs95

3168

68.

90E

-06

TG

−0.

038

0.00

80.

995

57.1

119

2063

341

rs28

4410

178.

93E

-06

GA

−0.

086

0.01

90.

335

82.7

AL

DH

4A1

TA

S1R

2

132

6684

281

rs64

2579

39.

63E

-06

AG

−0.

066

0.01

50.

357

69.7

CC

DC

28B

C1o

rf91

; DC

DC

2B; E

IF3I

;FA

M16

7B; I

QC

C; K

PNA

6; L

CK

;T

XL

NA

Bul

imia

ner

vosa

syn

drom

e fa

ctor

cas

e/co

ntro

l

218

7946

1018

8675

8043

rs14

4513

01.

08E

-07

AG

−0.0

560.

010.

974

86.4

NT

5C1B

863

2589

171

rs14

2014

203

8.83

E-0

7T

G−

0.12

60.

026

0.76

597

.4N

KA

IN3

2119

5314

421

rs77

6000

761.

17E

-06

AC

−0.

124

0.02

50.

588

97.1

CH

OD

L; T

MPR

SS15

1611

3869

601

rs11

7096

873

1.95

E-0

6C

T−

0.12

90.

027

0.65

497

.4PR

M1;

PR

M2;

PR

M3;

SO

CS1

; TN

P2

158

2889

7258

3198

282

rs98

5795

2.22

E-0

6T

G−

0.09

40.

020

0.65

294

.6D

AB

1

2231

4383

611

rs11

1383

589

2.25

E-0

6C

T−

0.08

70.

018

0.38

389

.2SM

TN


NIH


NIH


NIH


Wade et al.

Chr

Star

t (b

p,B

uild

37)

End

(bp

, Bui

ld37

)#

SNP

s (p

<10−5

)SN

P w

ith

low

est

plo

wes

t p-

val

ueE

ffec

t al

lele

Oth

er a

llele

Eff

ect

=Bet

aSE

Impu

tati

on R

2

Impu

ted

Alle

le f

req

(%)

Gen

es a

t th

ese

SNP

sG

enes

wit

hin

(app

rox)

+/−

50k

b

613

8426

032

1rs

1556

640

2.33

E-0

6T

C−

0.07

50.

016

0.43

788

.0PE

RP

513

4321

546

1rs

2993

622.

52E

-06

AG

−0.

062

0.01

30.

766

88.6

CA

TSP

ER

3PI

TX

1; P

CB

D2

463

8456

2963

8932

7827

rs14

5379

083

3.26

E-0

6G

A−0

.037

0.00

80.

813

51.0

1585

6992

0785

7192

079

rs80

4085

53.

32E

-06

CG

0.03

50.

007

0.97

263

.4PD

E8A

667

6452

4467

6532

796

rs28

6310

203.

45E

-06

GA

−0.

080

0.01

70.

718

92.5

1929

8975

3729

9185

774

rs12

9862

073.

90E

-06

GA

−0.

044

0.01

0.96

381

.7V

STM

2B

488

0533

3588

1267

974

rs11

5694

618

3.91

E-0

6A

G−

0.12

30.

027

0.76

097

.9A

FF1;

KL

HL

8C

4orf

36; H

SD17

B13

; HSD

17B

11

253

7270

3453

7565

424

rs56

1486

754.

50E

-06

TC

−0.

076

0.01

70.

905

94.2

517

7808

675

1rs

2910

124

5.80

E-0

6C

T−

0.05

90.

013

0.61

085

.8C

OL

23A

1

111

4226

143

1rs

6174

2849

5.82

E-0

6G

A−

0.17

90.

039

0.32

697

.5M

AG

I3PH

TF1

431

1527

5631

1561

783

rs74

8799

865.

86E

-06

GA

−0.

140

0.03

10.

619

97.5

313

3260

874

1rs

1170

8304

6.09

E-0

6C

T−

0.05

90.

013

0.59

885

.3C

DV

3

1587

7100

6687

7100

6610

rs80

2434

36.

14E

-06

AT

−0.

045

0.01

00.

901

83.1

515

0585

867

1505

9625

412

rs77

2477

46.

93E

-06

GA

−0.

054

0.01

20.

899

88.4

CC

DC

69G

M2A

316

3855

069

1rs

7866

1745

7.15

E-0

6C

T−

0.06

80.

015

0.64

590

.8

810

0864

111

rs69

9963

1(a)

8.01

E-0

6C

G−

0.09

00.

020

0.85

496

.5M

SRA

2134

3697

611

rs11

7124

364

8.93

E-0

6C

T−

0.16

00.

036

0.37

497

.7O

LIG

2

Pur

ging

via

sub

stan

ces

fact

or c

ase/

cont

rol

580

4065

661

rs13

8206

701

9.65

E-0

8A

G−

0.32

70.

061

0.53

598

.0R

ASG

RF2

813

4771

894

1347

8127

63

rs74

5661

336.

65E

-07

CT

−0.

249

0.05

00.

465

96.9

223

2298

076

1rs

1247

5512

6.82

E-0

7G

A0.

108

0.02

20.

349

54.3

NC

L; P

TM

A; P

DE

6D

358

1014

7158

1385

2810

rs13

0770

171.

00E

-06

CT

−0.0

730.

015

0.93

371

.0F

LN

BD

NA

SE1L

3

222

8667

258

2286

7257

96

rs10

1750

701.

94E

-06

AG

0.12

40.

026

0.34

175

.0SP

HK

AP;

CC

L20

376

2617

2476

2618

202

rs15

1645

93.

37E

-06

CT

−0.

270

0.05

80.

383

96.8

1070

0142

301

rs10

9980

353.

61E

-06

CT

−0.

151

0.03

30.

775

94.5

AT

OH

7

913

0503

612

1305

1797

35

rs51

4024

4.51

E-0

6A

G0.

061

0.01

30.

999

57.2

PK

N3

SET

; W

DR

34;

ZD

HH

C12

; Z

ER

1

831

5622

031

5627

13

rs14

2816

172

5.60

E-0

6C

T−

0.27

30.

060

0.52

497

.6C

SMD

1

260

1263

111

rs14

5433

814

6.25

E-0

6G

A−

0.23

90.

053

0.55

997

.6


NIH


NIH


NIH


Wade et al.

Chr

Star

t (b

p,B

uild

37)

End

(bp

, Bui

ld37

)#

SNP

s (p

<10−5

)SN

P w

ith

low

est

plo

wes

t p-

val

ueE

ffec

t al

lele

Oth

er a

llele

Eff

ect

=Bet

aSE

Impu

tati

on R

2

Impu

ted

Alle

le f

req

(%)

Gen

es a

t th

ese

SNP

sG

enes

wit

hin

(app

rox)

+/−

50k

b

331

0367

3831

0427

388

rs15

0620

37.

71E

-06

GT

−0.

083

0.01

80.

952

84.9

GA

DL

1

514

0668

925

1rs

1139

5153

79.

77E

-06

GT

−0.

163

0.03

70.

875

96.2

PCD

HG

A* ;

PC

DH

GB

* ; S

CL

25A

2;T

AF7

14-i

tem

cas

e/co

ntro

l dis

orde

red

eati

ng b

ehav

iour

s

1325

9940

4426

0225

9743

rs73

2291

67.

68E

-07

GA

0.08

90.

018

0.89

950

.1A

TP

8A2

115

2295

942

1524

0720

782

rs31

2066

71.

66E

-06

AG

−0.1

180.

025

0.95

684

.5F

LG

; F

LG

2; C

RN

N

639

1176

981

rs21

1520

02.

25E

-06

TG

0.09

80.

021

0.98

076

.8C

6orf

64; K

CN

K5

1012

8752

081

rs10

9062

333.

65E

-06

CT

−0.

288

0.06

20.

953

97.9

CA

MK

1D

2015

1207

4415

1210

812

rs11

0871

23(b

)3.

83E

-06

AG

−0.

120.

026

0.53

673

.8M

AC

RO

D2

580

4065

661

rs13

8206

701

4.25

E-0

6A

G−

0.42

50.

092

0.53

598

.0R

ASG

RF2

1610

6636

2710

6738

447

rs22

2143

34.

99E

-06

GT

−0.

087

0.01

90.

926

68.2

EM

P2T

EK

T5

410

0395

414

1004

1835

310

rs14

8915

469

7.90

E-0

6C

T−

0.27

90.

062

0.95

397

.9A

DH

7; C

4orf

17

Not

es:

* man

y ge

nes/

isof

orm

s in

that

fam

ily

(a) rs

6999

631

(Bul

imia

cas

e/co

ntro

l) is

123

5 bp

fro

m S

NP

rs14

1680

122

(p~8

.0×

10−

10, M

AF~

1.1%

) w

hich

fai

ls o

ur 2

% M

AF

filte

r. H

owev

er th

ere

is n

o ap

pare

nt a

ssoc

iatio

n si

gnal

apa

rt f

rom

thes

e tw

o SN

Ps e

ven

with

out t

hat f

ilter

.

(b) rs

1108

7123

(14

-ite

m c

ase/

cont

rol)

is in

a w

ide

bloc

k of

ass

ocia

ted

SNPs

dow

n to

p~1

.3×

10−

5 [4

0 w

ith p

≤ 1

0−4 ]

whi

ch f

ail t

he p

-val

ue f

ilter

use

d he

re.


NIH


NIH


NIH


Wade et al.

Tabl

e 3

Gen

e-ba

sed

asso

ciat

ions

at p

<10

−3

[plu

s ot

her

top

100

gene

s in

sam

e bl

ock]

for

eac

h ph

enot

ype.

Obt

aine

d us

ing

VE

GA

S so

ftw

are

base

d on

100

0 G

enom

es p

er-S

NP

p-va

lues

. Due

to s

oftw

are

limita

tions

this

only

con

side

rs S

NPs

fou

nd in

Hap

Map

Pha

se I

I, a

nd w

as n

ot r

un f

or th

e X

chr

omos

ome.

Gen

es h

ave

been

mer

ged

into

one

ent

ry a

nd s

how

n fo

r th

e lo

wes

t p-v

alue

whe

re m

ultip

le g

enes

in th

e sa

me

LD

blo

ckar

e as

soci

ated

. The

num

ber

of u

nder

lyin

g SN

Ps (

or r

ange

of

num

bers

, if

mul

tiple

gen

es)

is s

how

n. I

n m

ost c

ases

ther

e ar

e m

any

othe

r ge

nes

with

in ~

200

kbp.

Fig

ure

3 in

clud

es p

lots

of

per-

SNP

asso

ciat

ion

for

entr

ies

high

light

ed in

bol

d [r

efer

ence

SN

P fo

r th

e pl

ot m

ay d

iffe

r fr

om th

e on

e qu

oted

her

e].

Chr

Star

t (b

p; h

g19/

Bui

ld 3

7)E

nd (

bp)

Mos

t as

soci

ated

gen

e in

blo

ckM

ost

asso

ciat

ed H

apM

ap (

II)

SNP

wit

hin

mos

t as

soci

ated

gen

eO

ther

gen

e(s)

ass

ocia

ted,

top

100

for

phen

otyp

eG

ene

nam

eG

ene

p- v

alue

# SN

Ps

SNP

nam

ep-

valu

eE

ffec

t al

lele

Oth

er a

llele

Eff

ect

=Bet

aSE

Impu

tati

on R

2E

ffec

t al

lele

freq

(%

)

Ano

rexi

a sp

ectr

um f

acto

r ca

se/c

ontr

ol

714

1536

085

1416

4678

3O

R9A

44.

30E

-05

72rs

1285

957

1.00

E-0

6C

T−0

.056

0.01

20.

968

82.6

LO

C13

6242

; C

LE

C5A

313

0613

433

1310

6930

3A

STE

18.

50E

-05

84rs

1307

6493

3.34

E-0

5C

T−0

.043

0.01

00.

982

78.8

AT

P2C

1; N

EK

11

1629

6742

9929

7093

14SP

N1.

28E

-04

28rs

9933

310

3.30

E-0

5A

G0.

043

0.01

00.

638

58.9

QPR

T

1012

4320

180

1244

5933

8C

10or

f120

1.89

E-0

454

rs24

2103

14.

62E

-04

TC

0.04

80.

014

0.47

874

.0D

MB

T1

1087

3593

1188

4958

24L

DB

32.

78E

-04

154

rs28

0354

62.

79E

-04

GA

0.03

40.

009

0.84

354

.6O

PN4;

GR

ID1

274

6821

9874

8751

64L

OX

L3

2.87

E-0

436

rs17

0100

211.

00E

-05

TA

−0.

105

0.02

40.

696

95.8

ZN

HIT

4; W

BP1

; GC

S1; M

RPL

53;

CC

DC

142;

TT

C31

; LB

X2;

PC

GF1

; TL

X2;

DQ

X1;

AU

P1; H

TR

A2;

DO

K1;

C2o

rf65

1580

1373

1780

2636

43M

TH

FS3.

48E

-04

164

rs11

1398

31.

30E

-04

CA

−0.

033

0.00

90.

988

63.1

ST20

; C15

orf3

7; B

L2A

1

168

5116

4468

5164

60D

IRA

S33.

88E

-04

64rs

1206

9862

5.42

E-0

4G

A−

0.11

00.

032

0.40

695

.9

1010

2672

325

1027

4727

2FA

M17

8A4.

49E

-04

118

rs11

1907

902.

02E

-04

CA

0.03

20.

009

0.99

964

.1SE

MA

4G; M

RPL

43

511

8407

083

1185

8482

2D

MX

L1

6.14

E-0

412

9rs

4895

185

1.69

E-0

4A

G−

0.03

30.

009

0.99

966

.8

713

8818

523

1388

7454

6T

TC

267.

70E

-04

82rs

7798

474

6.90

E-0

5T

G−

0.03

90.

010

0.99

275

.4

886

0193

7686

1326

43L

RR

CC

19.

53E

-04

34rs

4150

880

1.70

E-0

5A

T−

0.04

50.

010

0.91

276

.2L

RR

CC

1; E

2F5;

C8o

rf59

458

2249

058

9478

5C

RM

P19.

67E

-04

205

rs37

7489

52.

00E

-05

TA

−0.

036

0.00

80.

981

50.4

Bul

imia

ner

vosa

spe

ctru

m f

acto

r ca

se/c

ontr

ol

514

0682

195

1408

9254

6SL

C25

A2

1.18

E-0

482

rs10

4913

091.

67E

-04

AG

−0.0

950.

025

0.54

796

.1T

AF

7; P

CD

HG

A1;

PC

DH

GA

3

242

3965

1542

7212

37K

CN

G3

1.58

E-0

413

3rs

1874

449

6.30

E-0

5T

G0.

030

0.00

70.

926

57.0

EM

L4;

CO

X7A

2L

1669

7962

7369

9978

89L

OC

3481

74-1

2.10

E−

0430

rs90

4809

4.30

E-0

5G

A−

0.03

30.

008

0.87

867

.6W

WP2

338

0350

7738

0711

33PC

LD

12.

48E

-04

85rs

6809

649

2.44

E-0

4T

C0.

036

0.01

00.

957

82.2

VIL

L

110

0930

1510

4802

01K

IF1B

2.54

E-0

417

3rs

1213

1785

1.50

E-0

5C

T−

0.04

20.

010

0.75

275

.4PG

D; U

BE

4B

710

0218

038

1003

9541

9PO

P73.

02E

-04

42rs

2217

955.

50E

-05

TC

−0.

029

0.00

71.

000

65.0

GN

B2;

GIG

YF1

; EPO

; TFR

2; A

CT

L6B

;Z

AN


NIH


NIH


NIH


Wade et al.

Chr

Star

t (b

p; h

g19/

Bui

ld 3

7)E

nd (

bp)

Mos

t as

soci

ated

gen

e in

blo

ckM

ost

asso

ciat

ed H

apM

ap (

II)

SNP

wit

hin

mos

t as

soci

ated

gen

eO

ther

gen

e(s)

ass

ocia

ted,

top

100

for

phen

otyp

eG

ene

nam

eG

ene

p- v

alue

# SN

Ps

SNP

nam

ep-

valu

eE

ffec

t al

lele

Oth

er a

llele

Eff

ect

=Bet

aSE

Impu

tati

on R

2E

ffec

t al

lele

freq

(%

)

1469

5176

4169

7090

72E

XD

L2

3.56

E-0

487

rs49

0270

41.

63E

-04

CG

−0.

028

0.00

70.

969

61.1

WD

R22

516

9064

292

1695

1038

1L

OC

1001

3189

74.

71E

-04

300

rs30

080

4.70

E-0

5C

G−

0.03

00.

007

0.99

760

.7D

OC

K2

517

5511

908

1755

4345

7FA

M15

3B5.

58E

-04

30rs

7443

800

3.22

E-0

4G

A−

0.02

70.

007

0.94

357

.5

2240

7425

0340

8062

93A

DSL

5.66

E-0

452

rs22

3531

82.

68E

-04

CT

−0.

037

0.01

00.

866

81.4

SGSM

3

2127

0967

9027

1447

71G

AB

PA5.

66E

-04

81rs

1048

2968

2.41

E-0

4C

A−

0.04

30.

012

0.95

989

.3A

TP5

J

1499

9477

3899

9778

52C

CN

K7.

06E

-04

87rs

4905

848

9.78

E-0

4G

A−

0.02

60.

008

0.79

648

.4C

CN

K

122

5965

530

2259

7816

4SR

P97.

29E

-04

101

rs12

1182

236.

34E

-04

AT

−0.

061

0.01

80.

412

90.4

SRP9

713

8728

265

1388

7454

6Z

C3H

AV

17.

56E

-04

123

rs18

1417

03.

40E

-05

AT

−0.

056

0.01

40.

797

90.2

TT

C26

123

7550

5523

8863

22E

2F2

8.03

E-0

464

rs32

1814

81.

97E

-04

AG

−0.

028

0.00

80.

905

54.7

DD

EFL

1; I

D3

222

8474

805

2284

9788

8D

KFZ

p547

H02

58.

18E

-04

158

rs23

9646

81.

47E

-04

AC

−0.

046

0.01

20.

786

87.1

C2o

rf83

1949

5884

6449

7150

93L

IN7B

8.35

E-0

471

rs80

441.

02E

-03

GT

−0.

024

0.00

70.

979

60.6

SNR

P70;

FL

J104

90; P

PFIA

3; H

RC

; TR

PM4

1631

4703

1631

5401

24T

GFB

1I1

8.98

E-0

444

rs71

8790

07.

53E

-04

AG

−0.

025

0.00

70.

956

48.5

AR

MC

5; S

LC

5A2;

C16

orf5

8; E

RA

F

1574

5286

6674

6600

81C

CD

C33

9.55

E-0

418

4rs

2930

313

1.23

E-0

4A

G−

0.05

90.

015

0.69

091

.1C

YP1

1A1

1543

5684

7843

9410

39L

CM

T2

9.58

E-0

462

rs24

1277

93.

33E

-04

AG

−0.

043

0.01

20.

917

89.8

AD

AL

; ZSC

AN

29; T

UB

GC

P4; T

P53B

P1;

HIS

PPD

2A; C

KM

T1B

; ST

RC

; CA

TSP

ER

2;M

AP1

A; T

GM

7

Pur

ging

via

sub

stan

ces

fact

or c

ase/

cont

rol

913

0374

567

1306

1704

7SH

2D3C

3.00

E-0

678

rs51

4024

5.00

E-0

6A

G0.

061

0.01

30.

999

57.2

STX

BP

1; C

9orf

117;

PT

RH

1; T

TC

16;

TO

R2A

; C

DK

9; F

PG

S; E

NG

122

9406

878

2294

7868

8C

1orf

969.

90E

-05

84rs

1637

716.

80E

-05

GA

−0.0

880.

022

0.36

962

.2R

AB

4A;

SPH

AR

317

0075

515

1701

5188

5SK

IL1.

12E

-04

67rs

1310

1192

3.80

E-0

5G

C0.

074

0.01

80.

934

83.4

CL

DN

11

635

9112

9236

2005

67M

APK

131.

22E

-04

72rs

7752

459

8.10

E-0

5C

T−

0.09

30.

024

0.94

989

.8M

APK

14; S

LC

26A

8; B

RPF

3

1238

7105

5639

2994

20C

PNE

81.

44E

-04

269

rs86

4324

6.20

E-0

5A

G−

0.05

30.

013

0.97

753

.6A

LG

10B

195

5502

1051

736

AG

RN

1.71

E-0

419

rs75

4595

21.

68E

-04

AG

−0.

177

0.04

70.

303

94.3

C1o

rf15

9

812

4084

919

1242

2231

8W

DR

672.

08E

-04

200

rs23

8516

53.

80E

-05

AC

0.06

10.

015

1.00

075

.2FA

M93

A

613

1466

460

1316

0467

3A

KA

P73.

22E

-04

181

rs37

7747

48.

10E

-05

AG

0.05

40.

014

0.97

563

.7A

KA

P7

222

8549

925

2286

8228

0C

CL

203.

71E

-04

81rs

1338

5901

4.00

E-0

6C

A0.

096

0.02

10.

811

84.0

SLC

19A

3

311

9885

878

1199

6294

5G

PR15

64.

16E

-04

169

rs46

7682

21.

07E

-04

TG

−0.

101

0.02

60.

963

92.9


NIH


NIH


NIH


Wade et al.

Chr

Star

t (b

p; h

g19/

Bui

ld 3

7)E

nd (

bp)

Mos

t as

soci

ated

gen

e in

blo

ckM

ost

asso

ciat

ed H

apM

ap (

II)

SNP

wit

hin

mos

t as

soci

ated

gen

eO

ther

gen

e(s)

ass

ocia

ted,

top

100

for

phen

otyp

eG

ene

nam

eG

ene

p- v

alue

# SN

Ps

SNP

nam

ep-

valu

eE

ffec

t al

lele

Oth

er a

llele

Eff

ect

=Bet

aSE

Impu

tati

on R

2E

ffec

t al

lele

freq

(%

)

514

0603

077

1408

9254

6PC

DH

B15

4.61

E-0

489

rs10

0449

361.

20E

-05

CT

−0.

151

0.03

50.

860

95.6

PCD

HB

14; S

LC

25A

2; T

AF7

; PC

DH

GA

* ;PC

DH

GB

*

221

6807

313

2169

6749

4PE

CR

5.90

E-0

411

3rs

9341

544.

20E

-05

TC

0.05

80.

014

0.97

869

.0M

RE

G; T

ME

M16

9

357

9941

2658

1579

77FL

NB

7.96

E-0

428

7rs

1307

7017

1.00

E-0

6C

T−

0.07

30.

015

0.93

371

.0

782

9932

2183

2783

24SE

MA

3E9.

90E

-04

425

rs27

1318

91.

39E

-04

CT

−0.

050

0.01

30.

996

53.9

14-i

tem

cas

e/co

ntro

l for

dis

orde

red

eati

ng b

ehav

iour

s

115

2184

557

1523

8672

8F

LG

2"0

" (n

ext

low

est

is3E

-6)

74rs

3120

667

1.66

E-0

6A

G−0

.118

0.02

50.

956

84.5

FL

G;

CR

NN

; H

RN

R

1091

0617

0591

1807

53IF

IT3

1.31

E-0

474

rs62

7524

1.83

E-0

5C

A−

0.07

60.

018

0.99

847

.8IF

IT1L

; IFI

T1;

IFI

T5;

IFI

T2

565

2223

8365

3768

50E

RB

B2I

P1.

42E

-04

134

rs25

1614

5.70

E-0

5C

G−

0.10

40.

026

0.85

285

.2E

RB

B2I

P

514

0588

290

1406

8361

2PC

DH

B15

2.15

E-0

489

rs29

1033

05.

07E

-04

GT

−0.

081

0.02

30.

990

83.6

PCD

HB

12; P

CD

HB

13; P

CD

HB

14;

SCL

25A

2

223

4160

216

2342

5570

1A

TG

16L

12.

65E

-04

128

rs67

5989

61.

70E

-04

AG

0.07

00.

019

0.86

358

.4SA

G

317

0075

515

1701

5188

5C

LD

N11

2.81

E-0

481

rs42

9223

12.

45E

-04

GC

0.09

20.

025

0.79

180

.4SK

IL

469

9572

1381

837

PCG

F33.

73E

-04

93rs

6816

483

7.00

E-0

4C

T−

0.06

40.

019

0.96

568

.5C

PLX

1; S

PON

2; K

IAA

1530

1010

2672

325

1028

0099

8L

ZT

S23.

81E

-04

63rs

8070

291.

86E

-04

CT

0.07

70.

021

0.86

972

.5FA

M17

8A; S

EM

A4G

; MR

PL43

; C10

orf2

;PD

ZD

7; S

FXN

3

1169

9244

0770

0534

86T

ME

M16

A4.

08E

-04

210

rs25

0917

59.

80E

-05

TA

0.10

60.

027

0.58

677

.8FA

DD

1918

0459

0418

1249

11K

CN

N1

4.53

E-0

476

rs48

0810

53.

67E

-04

CT

−0.

065

0.01

80.

980

67.4

CC

DC

124;

AR

RD

C2

415

6587

877

1567

2805

6G

UC

Y1B

35.

09E

-04

139

rs17

0335

852.

52E

-04

GA

0.12

80.

035

0.36

678

.4G

UC

Y1A

3

1627

4719

3328

0748

30G

SG1L

5.18

E-0

431

2rs

1645

336

1.24

E-0

3T

C−

0.06

80.

021

0.99

875

.7G

TF3

C1;

KIA

A05

56

195

5502

1051

736

C1o

rf15

95.

70E

-04

31rs

6689

308

5.62

E-0

4A

G−

0.08

70.

025

0.88

583

.9A

GR

N

1738

2716

840

4625

3A

TP2

A3

5.97

E-0

485

rs99

1420

32.

96E

-04

GA

0.21

90.

060

0.45

895

.2Z

ZE

F1

1954

5542

554

5686

7Z

NR

F47.

27E

-04

69rs

5295

153.

76E

-03

AG

0.07

40.

025

0.46

952

.3Z

NR

F4

469

6817

2869

6966

20U

GT

2B10

9.71

E−

0462

rs93

2903

41.

29E

-03

TC

0.09

60.

030

0.82

789

.6U

GT

2B10

Not

e:

* = m

any

gene

s in

that

fam

ily


NIH


NIH


NIH


Wade et al.

Tabl

e 4

Rep

licat

ion

of p

revi

ous

stud

ies:

Per

-SN

P as

soci

atio

n p-

valu

es f

or S

NPs

rep

orte

d as

soci

ated

with

AN

in p

revi

ous

liter

atur

e (a

s la

bele

d) w

here

ava

ilabl

e in

our

ana

lysi

s. r

s674

386

(fro

m B

row

n et

al)

was

not

avai

labl

e, o

bser

ved

or im

pute

d. I

mpu

ted

dosa

ges

cove

r al

l ~25

57 p

heno

type

d in

divi

dual

s. O

bser

ved

geno

type

s co

ver

~121

7 ph

enot

yped

indi

vidu

als

(rs1

7725

255,

238

3378

, rs8

3099

8); ~

1497

(rs

5331

23);

othe

rwis

e ~2

550

(les

s m

inor

dro

pout

for

eac

h ph

enot

ype)

.

Rep

orte

d SN

P

p-va

lues

for

Ano

rexi

a N

ervo

sa s

pect

rum

Fac

tor

case

/Con

trol

p-va

lues

for

Bul

imia

Ner

vosa

spe

ctru

m c

ase/

Con

trol

p-va

lues

for

Tab

let

Pur

ging

fac

tor

case

/Con

trol

p-va

lues

for

14-

item

cas

e/C

ontr

ol d

isor

dere

dea

ting

beh

avio

urIm

pute

dM

AF

(%

) -

here

MA

F (

%)i

nre

fere

nced

pape

r [A

Nca

se;

cont

rol]

obse

rved

gen

otyp

es10

00G

dos

age

obse

rved

gen

otyp

es10

00G

dos

age

obse

rved

gen

otyp

es10

00G

dos

age

obse

rved

gen

otyp

es10

00G

dos

age

SNPs

ass

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6510

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3123

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3226

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rs76

2432

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567

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9046

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931

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229

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9811

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5192

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927

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5364

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190.

198

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577

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633

41.2

42.9


Genetic variants associated with disordered eating

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Transcript of Genetic variants associated with disordered eating