Genomic variants at 20p11 were associated with body fat mass in the European population

OBJECTIVE: Body fat mass (BFM) is more homogeneous and accurate than body total mass in measuring obesity, but has rarely been studied. Aiming to uncover the genetic basis of fat-induced obesity, we performed a genome-wide association meta-analysis of BFM, after adjustment by body lean mass, in the European population. METHODS: Three samples of European ancestry were included into the meta-analysis: the Framingham heart study (FHS, N=6,004), the Kansas-city osteoporosis study (KCOS, N=2,207) and the Omaha osteoporosis study (OOS, N=968). RESULTS: At genome-wide significance level (α=5.0×10(−8)), we identified a cluster of 10 SNPs at chromosomal region 20p11 that were associated with BFM (lead SNP rs2069126 p=1.82×10(−9), closest gene SLC24A3) in 9,179 subjects. One of the top SNPs rs6046308 (p=3.74×10(−8)) is nominally significant for body fat percentage in another independent study (p=0.03, N=75,888), and is reported to trans-regulate the expression of MPZ gene at 1q23.3 (unadjusted p=9.78×10(−6), N=1,490). Differential gene expression analysis demonstrates that SLC24A3 and CFAP61 at the identified locus are differentially expressed in tissues of people with versus without obesity (p=3.40×10(−5) and 8.72×10(−4), N=126 and 70), implying their potential role in fat development. CONCLUSIONS: Our results may provide new insights into the biological mechanism that underlies fat-induced obesity pathology.