Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, JAPAN.
Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Iwate, JAPAN.
Med Sci Sports Exerc. 2018 Dec;50(12):2433-2441. doi: 10.1249/MSS.0000000000001712.
Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results.
We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study.
We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples.
We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.
尽管有几个遗传因素可能在休闲时间运动行为中发挥作用，但目前没有全基因组关联的显著证据，候选基因复制研究的结果也不一致。
我们使用日本多机构合作队列（J-MICC）研究的 13980 个发现样本和爱知县癌症中心-2 医院基于人群的流行病学研究计划（HERPACC-2）的 2036 个复制样本，进行了休闲时间运动行为的两阶段全基因组关联研究和候选单核苷酸多态性（SNP）关联研究。休闲时间体力活动使用自我管理问卷进行测量，询问锻炼的类型、频率和持续时间。将进行≥4 MET·h·wk 休闲时间体力活动的参与者定义为表现出休闲时间运动行为。在发现和复制样本中使用混合线性回归模型进行关联测试，然后在荟萃分析中合并结果。此外，我们还测试了来自先前全基因组关联研究的六个候选遗传变异。
我们发现一个位于 NPSR1 和 DPY19L1 之间基因间区域的新 SNP（rs10252228）与发现样本中的休闲时间运动行为显著相关。这种关联在复制样本中也很显著（荟萃分析综合 P 值=2.2×10）。与 rs10252228 相关的几个 SNP 与骨骼肌、心脏、全血和神经系统中 DP19L1 和 DP19L2P1 的基因表达显著相关。在候选 SNP 中，DNAPTP6 中的 rs12612420 在发现样本中具有显著意义，但在复制样本中没有。
我们确定了一个与定期休闲时间运动行为相关的新遗传变异。需要进一步的功能研究来验证这些变异在运动行为中的作用。
