Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosaDuncan, L., Yilmaz, Z., Gaspar, H., Walters, R., Goldstein, J., Anttila, V., Bulik-Sullivan, B., Ripke, S., Thornton, L., Hinney, A., Daly, M., Sullivan, P. F., Zeggini, E., Breen, G., Bulik, C. M., Eating Disorders Working Group of the Psychiatric Genomics Consortium & Kas, M. J. H., 1-Sep-2017, In : American Journal of Psychiatry. 174, 9, p. 850-858
Research output: Contribution to journal › Article › Academic › peer-review
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 [h(2)SNP]), 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 h(2)SNP 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.
|Journal||American Journal of Psychiatry|
|Publication status||Published - 1-Sep-2017|
- Journal Article, PSYCHIATRIC-DISORDERS, EATING-DISORDERS, RISK, GWAS, SCHIZOPHRENIA, METAANALYSIS, TRAITS, UPDATE