A Copy Number Variant on Chromosome 20q13.3 Implicated in Thinness and Severe Obesity

• Published in: Journal of Obesity 2015-01, Vol.2015 (2015), p.246-252
• Main Authors: Adams, Ted D., Lewis, Tracey, Mao, Rong, Xin, Yuanpei, Hasstedt, Sandra J., Hunt, Steven C.
• Format: Article
• Language: English
• Subjects: ADP-Ribosylation Factors - genetics; Adult; Aged; Aged, 80 and over; Alleles; Analysis; Body Mass Index; Chromosomes; Chromosomes, Human, Pair 20; Colleges & universities; Comparative Genomic Hybridization; Copy number variations; Deoxyribonucleic acid; DNA; DNA Copy Number Variations; Drug dosages; Families & family life; Female; Genes; Genetic aspects; Genetic Pleiotropy; Genetic Predisposition to Disease; Genetic variation; Genetics; Genome-Wide Association Study; Genomes; Genomics; Genotype; Humans; Male; Medicine; Middle Aged; Obesity; Obesity, Morbid - genetics; Pedigree; Physiological aspects; Reference Values; Risk factors; Sequence Deletion; Software; Thinness - genetics; Young Adult
• ISSN: 2090-0708; 2090-0716
• DOI: 10.1155/2015/623431

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.