Total deletion burden was associated with a 0.41 cm decrease in height per megabase, and five new rare copy number variant loci were associated with anthropometric traits.
Meta-Analysis (n=191,161)
Sí
Do rare copy number variants (CNVs) and overall CNV burden affect anthropometric traits such as height, weight, BMI, and waist-to-hip ratio in European adults?
Rare copy number variants and overall CNV deletion burden significantly impact key anthropometric traits including height, weight, and BMI, highlighting the contribution of rare structural genomic variations to complex human traits.
Mean Difference: -0.41
valor p: p=2.5 × 10-10
Abstract There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01–0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m 2 ). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m 2 for each Mb of total deletion burden ( P = 2.5 × 10 −10 , 6.0 × 10 −5 , and 2.9 × 10 −3 ). Our study provides evidence that the same genes (e.g., MC4R , FIBIN , and FMO5 ) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.
Macé et al. (Mon,) conducted a meta-analysis in Anthropometric traits (height, weight, BMI, waist-to-hip ratio) (n=191,161). Rare copy number variants (CNVs) vs. Copy neutral state (population average) was evaluated on Change in height per Mb of total deletion burden (MD -0.41 cm, p=2.5 × 10-10). Total deletion burden was associated with a 0.41 cm decrease in height per megabase, and five new rare copy number variant loci were associated with anthropometric traits.