engleski

WTCCC3 and GCAN: A Genomewide Association Study of Anorexia Nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by the maintenance of dangerously low body weight. We established the Genetic Consortium for Anorexia Nervosa which is an unprecedented worldwide collaboration combining existing DNA samples of AN patients into a single resource. As part of the Wellcome Trust Case Control Consortium 3 we conducted the largest genome-wide association study of AN to date combining 2, 907 AN cases, originating from 15 different countries of European ancestry, and 14, 860 ancestrally matching controls. Individual association analyses were carried out in each ancestry stratum and then meta-analysed across all 15 strata. Seventy-six SNPs were taken forward for in silico and de novo replication in another 15 datasets of European ancestry and from Japan. Global meta-analysis across discovery and replication datasets, comprising a total of 5, 551 AN cases and 21, 080 controls, was then performed. Suggestively associated SNPs were rs9839776 (p=3.01x10-7) within SOX2OT and rs17030795 (p=5.84x10-6) within PPP3CA in the main analysis and rs1523921 (p=5.76x10-6) located between CUL3 and FAM124B and rs1886797 (p=8.05x10-6) located near SPATA13 in Europeans only. In comparing the discovery to the replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P = 4x10-6). This suggests that many true findings exist but that our sample, the largest yet reported, was under-powered for their detection at the genome-wide level and that accrual of large genotyped AN case-control samples should be an immediate priority for the field.

anorexia nervosa; eating disorders; genetics; genome-wide association study; WTCCC

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