A copy number variant on chromosome 20q13.3 implicated in thinness and severe obesity

Background/objectives. to identify copy number variants (cnvs) which are associated with body mass index (bmi). subjects/methods. cnvs were identified using array comparative genomic hybridization (acgh) on members of pedigrees ascertained through severely obese (bmi ≥ 35 kg/m2) sib pairs (86 pedigrees) and thin (bmi ≤ 23 kg/m2) probands (3 pedigrees). association was inferred through pleiotropy of bmi with cnv log 2 intensity ratio. results. a 77-kilobase cnv on chromosome 20q13.3,confirmed by real-time qpcr,exhibited deletions in the obese subjects and duplications in the thin subjects (p=2.2×10-6). further support for the presence of a deletion derived from inference by likelihood analysis of null alleles for snps residing in the region. conclusions. one or more of 7 genes residing in a chromosome 20q13.3 cnv region appears to influence bmi. the strongest candidate is arfrp1,which affects glucose metabolism in mice. © 2015 sandra j. hasstedt et al.