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Obesity (Silver Spring). 2017 Apr;25(4):757-764. doi: 10.1002/oby.21775. Epub 2017 Feb 22.

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

Pei YF#1,2, Ren HG#3, Liu L2,4, Li X2,4, Fang C5, Huang Y5, Hu WZ2,4, Kong WW2,4, Feng AP2,4, You XY2,4, Zhao W2,4, Shen H6, Tian Q6, Zhang YH1,2, Deng HW6, Zhang L2,4.

Author information

1
Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Soochow University, Suzhou, PR China.
2
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, PR China.
3
Laboratory of Molecular Neuropathology, Department of Pharmacology, School of Pharmaceutical Sciences, Medical College, Soochow University, Suzhou, PR China.
4
Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College, Soochow University, Suzhou, PR China.
5
Department of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, PR China.
6
Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.
#
Contributed equally

Abstract

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 (α = 5.0×10-8 ), a cluster of 10 single-nucleotide polymorphisms (SNPs) at chromosomal region 20p11 that were associated with BFM (lead SNP rs2069126, P = 1.82×10-9 , closest gene SLC24A3) was identified in 9,179 subjects. One of the top SNPs, rs6046308 (P = 3.74×10-8 ), 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 = 9.78×10-6 , 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 = 3.40×10-5 and 8.72×10-4 , 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.

PMID:
28224759
PMCID:
PMC5373963
DOI:
10.1002/oby.21775
[Indexed for MEDLINE]
Free PMC Article

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