Chen Guanjie, Doumatey Ayo P, Zhou Jie, Lei Lin, Bentley Amy R, Tekola-Ayele Fasil, Adebamowo Sally N, Baker Jennifer L, Fasanmade Olufemi, Okafor Godfrey, Eghan Benjamin, Agyenim-Boateng Kofi, Amoah Albert, Adebamowo Clement, Acheampong Joseph, Johnson Thomas, Oli Johnnie, Shriner Daniel, Adeyemo Adebowale A, Rotimi Charles N
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA, 20892.
University of Lagos, College of Medicine, Endocrine and Metabolic Unit, Lagos, Nigeria.
Obesity (Silver Spring). 2017 Apr;25(4):794-800. doi: 10.1002/oby.21804. Epub 2017 Mar 13.
The prevalence of obesity varies between ethnic groups. No genome-wide association study (GWAS) for body mass index (BMI) has been conducted in continental Africans.
We performed a GWAS for BMI in 1,570 West Africans (WA). Replication was conducted in independent samples of WA (n = 1,411) and African Americans (AA) (n = 9,020).
We identified a novel genome-wide significant African-specific locus for BMI (SEMA4D, rs80068415; minor allele frequency = 0.008, P = 2.10 × 10 ). This finding was replicated in independent samples of WA (P = 0.013) and AA (P = 0.017). Individuals with obesity had higher serum SEMA4D levels compared to those without obesity (P < 0.0001), and elevated levels of serum SEMA4D were associated with increased obesity risk (OR = 4.2, P < 1 × 10 ). The prevalence of obesity was higher in individuals with the CT versus TT genotypes (55.6% vs. 22.9%).
A novel variant in SEMA4D was significantly associated with BMI. Carriers of the C allele were 4.6 BMI units heavier than carriers of the T allele (P = 0.0007). This variant is monomorphic in Europeans and Asians, highlighting the importance of studying diverse populations. While there is evidence for the involvement of SEMA4D in inflammatory processes, this study is the first to implicate SEMA4D in obesity pathophysiology.
肥胖症的患病率在不同种族群体之间存在差异。尚未在非洲大陆人群中开展过关于体重指数（BMI）的全基因组关联研究（GWAS）。
我们对1570名西非人群（WA）进行了BMI的GWAS研究。在独立的WA样本（n = 1411）和非裔美国人（AA）样本（n = 9020）中进行了重复验证。
我们鉴定出一个新的全基因组显著的非洲特异性BMI位点（SEMA4D，rs80068415；次要等位基因频率 = 0.008，P = 2.10×10 ）。这一发现在独立的WA样本（P = 0.013）和AA样本（P = 0.017）中得到了重复验证。与非肥胖者相比，肥胖个体的血清SEMA4D水平更高（P < 0.0001），且血清SEMA4D水平升高与肥胖风险增加相关（OR = 4.2，P < 1×10 ）。CT基因型个体的肥胖患病率高于TT基因型个体（55.6%对22.9%）。
SEMA4D中的一个新变异与BMI显著相关。C等位基因携带者的BMI比T等位基因携带者重4.6个单位（P = 0.0007）。该变异在欧洲人和亚洲人中是单态的，凸显了研究不同人群的重要性。虽然有证据表明SEMA4D参与炎症过程，但本研究首次表明SEMA4D与肥胖病理生理学有关。
