The aims of the present review are to apply a recent risk factor approach (H. C. Kraemer et al., 1997) to putative risk factors for eating disorders, to order these along a timeline, and to deduce general taxonomic questions. Putative risk factors were classified according to risk factor type, outcome (anorexia nervosa, bulimia nervosa, binge-eating disorder, full vs. partial syndromes), and additional factor characteristics (specificity, potency, need for replication). Few of the putative risk factors were reported to precede the onset of the disorder. Many factors were general risk factors; only few differentiated between the 3 eating disorder syndromes. Common risk factors from longitudinal and cross-sectional studies were gender, ethnicity, early childhood eating and gastrointestinal problems, elevated weight and shape concerns, negative self-evaluation, sexual abuse and other adverse experiences, and general psychiatric morbidity. Suggestions are made for the conceptualization of future risk factor studies.

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Objective To conduct a genome-wide association study (GWAS) of anorexia nervosa and to calculate genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Method Following uniform quality control and imputation using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, we performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression (LDSC) was used to calculate genome-wide common variant heritability [ hSNP2, partitioned heritability, and genetic correlations (rg)] between anorexia nervosa and other phenotypes. Results Results were obtained for 10,641,224 single nucleotide polymorphisms (SNPs) and insertion-deletion variants with minor allele frequency > 1% and imputation quality scores > 0.6. The hSNP2 of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. We identified one genome-wide significant locus on chromosome 12 (rs4622308, p=4.3×10−9) 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 (HDL) cholesterol, and significant negative genetic correlations between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Conclusions Anorexia nervosa is a complex heritable phenotype for which we have found the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. Our results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

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