期刊
OBESITY
卷 25, 期 4, 页码 757-764出版社
WILEY
DOI: 10.1002/oby.21775
关键词
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资金
- National Natural Science Foundation of China [31501026, 31571291, 31100902]
- Natural Science Foundation of Jiangsu Province of China [BK20150323]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
- NIH [P50AR055081, R01AG026564, R01AR050496, RC2DE020756, R01AR057049,, R03TW008221]
- Franklin D. Dickson/Missouri Endowment
- Edward G. Schlieder Endowment
- Soochow university [Q413900114, Q413900214]
- Jiangsu Province [201610285040Z]
- Jiangsu Higher Education Institutions
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, a genome-wide association meta-analysis of BFM, after adjustment by body lean mass, was performed in the European population. Methods: Three samples of European ancestry were included in the meta-analysis: the Framingham Heart Study (N = 6,004), the Kansas City osteoporosis study (N = 2,207), and the Omaha osteoporosis study (N = 968). Results: At the genome-wide significance level (alpha = 5.0 X 10(-8)), a cluster of 10 single-nucleotide polymorphisms (SNPs) at chromosomal region 20p11 that were associated with BFM (lead SNP rs2069126, P = 1.82 X 10(-9), closest gene SLC24A3) was identified in 9,179 subjects. One of the top SNPs, rs6046308 (P = 3.74 x 10(-8)), was found to be nominally significant for body fat percentage in another independent study (P = 0.03, N = 75,888) and was reported to transregulate the expression of the MPZ gene at 1q23.3 (unadjusted P = 9.78 x 10(-6) , N = 1,490). Differential gene expression analysis demonstrated that SLC24A3 and CFAP61 at the identified locus were differentially expressed in tissues of people with versus without obesity (P = 3.40 x 10(-5) and 8.72 x 10(-4), N = 126 and 70), implying their potential role in fat development. Conclusions: These results may provide new insights into the biological mechanism that underlies fat-induced obesity pathology.
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