Identification of rare variants in CADM1 in patients with anorexia nervosa

Abstract

As a polygenic psychiatric disorder, the genetics of anorexia nervosa (AN) remains largely unexplored. Recently a large GWAS meta-analysis identified a significant SNP (rs6589488) as associated with AN. We suggested that rs6589488 might have gotten its association as being in linkage disequilibrium with unknown variants or functional intronic variants. In a selective cohort containing 51 patients diagnosed with restrictive subtype AN, we screened the whole coding region of the CADM1gene by Sanger sequencing and further investigated if these variants are associated with specific outcome. Only 13 single nucleotide polymorphisms, including 2 missense variants, 2 synonymous variants, 2 variants located at 5'-UTR and 7 intronic variants, including rs6589488, were identified in our AN cohort. The 2 missense variants, p.Val5Leu and p.Asp285Glu were not predicted to be deleterious. In conclusion, the intronic initial variant appears to be not associated with causative coding variant in the vicinity. If CADM1 is not the AN predisposition factor, the causative variant probably lies within 1 Mb of CADM1. Interestingly, among the 7 closest genes to CADM1, the nicotinamide N-methyltransferase (NNMT) gene is known to be associated with obesity. We suggest that the intronic variant in CADM1 could be in linkage disequilibrium with other causative variants located in NNMT.