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

Abstract EN

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 log2 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.