A genome-wide association study of anorexia nervosa

Abstract

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Influence of TFAP2B and KCTD15 genetic variability on personality dimensions in anorexia and bulimia nervosa

“…In contrast, no associations were found for AN risk, which is consistent with the findings by Brandys et al. (2010), who failed to find a significant effect of a KCTD15 polymorphism previously associated with obesity in AN patients; as well as with several GWAS, which have not identified any KCTD15 SNP related to AN risk (Boraska et al., 2014; Hinney et al., 2017; Wang et al., 2011). In this regard, several loci in or near KCTD15 have repeatedly been associated with obesity in a number of GWAS and replication studies (Mei et al., 2012; Paternoster et al., 2011; Thorleifsson et al., 2009; Willer et al., 2009).…”

Forschungsschwerpunkte in der Österreichischen Kinder- und Jugendpsychiatrie – 2007 bis 2017

“…Aus den Publikationen, die aus den 5 Schwerpunktthemen hervorgegangen sind werden 5 wichtige Publikationen ausgewählt, aus den weiteren 6 Themen 2. Die meisten der 284 Publikationen erscheinen zu 5 Themen: Essstörungen (n = 34) [20][21][22][23][24], gefolgt von Forensik (n = 23) [25][26][27][28][29], Neuropädiatrie (n = 22) [30][31][32][33], Psychosen und Prodrome (n = 19) [34][35][36][37][38] und Suizidalität (n = 17) [39][40][41][42][43]. Diese 5 Themen ergaben 115 Publikationen, was etwa 41 % der Artikel ausmacht.…”

The role of endocannabinoids in the control of eating disorders

“…The most accredited model is the bio-psycho-social model in which more than one factor develops from genetic to family, social and cultural factors [16]. Several studies (on families, twins, DNA) [17][18][19][20][21][22][23] seem to suggest that about 50% of the risk is due to genetic factors. Environmental risk factors can be multiple and are divided into early and late; Early Risk Factors are all those conditions that interfere with the early stages of neuro-development and maturation of stress response systems and include intrauterine life conditions, perinatal complications and early alterations in relationship with figures of care [24].…”