TY - JOUR
T1 - Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa
AU - Duncan, Laramie
AU - Yilmaz, Zeynep
AU - Gaspar, Helena
AU - Walters, Raymond
AU - Goldstein, Jackie
AU - Anttila, Verneri
AU - Bulik-Sullivan, Brendan
AU - Ripke, Stephan
AU - Thornton, Laura
AU - Hinney, Anke
AU - Daly, Mark
AU - Sullivan, Patrick F
AU - Zeggini, Eleftheria
AU - Breen, Gerome
AU - Bulik, Cynthia M
AU - Eating Disorders Working Group of the Psychiatric Genomics Consortium
AU - Kiezebrink, Kirsty
PY - 2017/9/1
Y1 - 2017/9/1
N2 - OBJECTIVE: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes.METHOD: Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes.RESULTS: Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h2SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes.CONCLUSIONS: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.
AB - OBJECTIVE: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes.METHOD: Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes.RESULTS: Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h2SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes.CONCLUSIONS: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.
KW - Anorexia Nervosa/genetics
KW - Case-Control Studies
KW - Genetic Predisposition to Disease/genetics
KW - Genome-Wide Association Study
KW - Humans
KW - Linkage Disequilibrium/genetics
KW - Phenotype
KW - Polymorphism, Single Nucleotide/genetics
U2 - 10.1176/appi.ajp.2017.16121402
DO - 10.1176/appi.ajp.2017.16121402
M3 - Article
C2 - 28494655
SN - 0002-953X
VL - 174
SP - 850
EP - 858
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 9
ER -
