Reddon Hudson, Gerstein Hertzel C, Engert James C, Mohan Viswanathan, Bosch Jackie, Desai Dipika, Bailey Swneke D, Diaz Rafael, Yusuf Salim, Anand Sonia S, Meyre David
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada.
Sci Rep. 2016 Jan 4;6:18672. doi: 10.1038/srep18672.
Physical activity (PA) has been shown to reduce the impact of FTO variation and obesity genetic risk scores (GRS) on BMI. We examined this interaction using a quantitative measure of PA and two adiposity indexes in a longitudinal multi-ethnic study. We analyzed the impact of PA on the association between 14 obesity predisposing variants (analyzed independently and as a GRS) and baseline/follow-up obesity measures in the multi-ethnic prospective cohort EpiDREAM (17423 participants from six ethnic groups). PA was analyzed using basic (low-moderate-high) and quantitative measures (metabolic equivalents (METS)), while BMI and the body adiposity index (BAI) were used to measure obesity. Increased PA was associated with decreased BMI/BAI at baseline/follow-up. FTO rs1421085, CDKAL1 rs2206734, TNNl3K rs1514176, GIPR rs11671664 and the GRS were associated with obesity measures at baseline and/or follow-up. Risk alleles of three SNPs displayed nominal associations with increased (NTRK2 rs1211166, BDNF rs1401635) or decreased (NPC1 rs1805081) basic PA score independently of BMI/BAI. Both basic and quantitative PA measures attenuated the association between FTO rs1421085 risk allele and BMI/BAI at baseline and follow-up. Our results show that physical activity can blunt the genetic effect of FTO rs1421085 on adiposity by 36-75% in a longitudinal multi-ethnic cohort.
体育活动（PA）已被证明可降低FTO基因变异和肥胖遗传风险评分（GRS）对体重指数（BMI）的影响。在一项纵向多民族研究中，我们使用PA的定量测量方法和两个肥胖指数来研究这种相互作用。我们分析了PA对14个肥胖易感变异（单独分析和作为GRS分析）与多民族前瞻性队列EpiDREAM（来自六个民族的17423名参与者）中基线/随访肥胖测量之间关联的影响。使用基本（低-中-高）和定量测量方法（代谢当量（METS））分析PA，同时使用BMI和身体肥胖指数（BAI）来测量肥胖。PA增加与基线/随访时BMI/BAI降低相关。FTO rs1421085、CDKAL1 rs2206734、TNNl3K rs1514176、GIPR rs11671664和GRS与基线和/或随访时的肥胖测量相关。三个单核苷酸多态性（SNP）的风险等位基因与增加（NTRK2 rs1211166、BDNF rs1401635）或降低（NPC1 rs1805081）的基本PA评分存在名义上的关联，独立于BMI/BAI。基本和定量PA测量方法均减弱了FTO rs1421085风险等位基因与基线和随访时BMI/BAI之间的关联。我们的结果表明，在纵向多民族队列中，体育活动可使FTO rs1421085对肥胖的遗传效应减弱36%-75%。
