Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
Hum Mol Genet. 2020 May 8;29(7):1218-1228. doi: 10.1093/hmg/ddaa040.
Previous studies have shown that men and women have different genetic architectures across many traits. However, except waist-to-hip ratio (WHR) and waist circumference (WC), it remains unknown whether the genetic effects of a certain trait are weaker or stronger on men/women. With ~18 000 Taiwan Biobank subjects, we comprehensively investigate sexual heterogeneity in autosomal genetic effects, for traits regarding cardiovascular health, diabetes, kidney, liver, anthropometric profiles, blood, etc. 'Gene-by-sex interactions' (G $\times$ S) were detected in 18 out of 26 traits, each with an interaction P-value (${{P}}{{INT}}$) less than $0.05/104={0.00048}$, where 104 is the number of tests conducted in this study. The most significant evidence of G $\times$ S was found in WHR (${{P}}{{INT}}$ = 3.2 $\times{{10}}^{-{55}}$) and WC (${{P}}_{{INT}}$ = 2.3$\times{{10}}^{-{41}}$). As a novel G$\times$S investigation for other traits, we here find that the autosomal genetic effects are weaker on women than on men, for low-density lipoprotein cholesterol (LDL-C), uric acid (UA) and diabetes-related traits such as fasting glucose and glycated hemoglobin. For LDL-C and UA, the evidence of G$\times$S is especially notable in subjects aged less than 50 years, where estrogen can play a role in attenuating the autosomal genetic effects of these two traits. Men and women have systematically distinct environmental contexts caused by hormonal milieu and their specific society roles, which may trigger diverse gene expressions despite the same DNA materials. As many environmental exposures are difficult to collect and quantify, sex can serve as a good surrogate for these factors.
先前的研究表明，男性和女性在许多特征上的遗传结构存在差异。然而，除了腰臀比（WHR）和腰围（WC）之外，尚不清楚某个特征的遗传效应对男性/女性是较弱还是较强。利用约 18000 名台湾生物库受试者，我们全面研究了常染色体遗传效应在心血管健康、糖尿病、肾脏、肝脏、人体测量学特征、血液等方面的性别差异。在 26 个特征中的 18 个特征中检测到了“基因-性别相互作用”（G $\times$ S），每个特征的交互 P 值（${{P}}{{INT}}$）小于 0.05/104=0.00048，其中 104 是本研究中进行的测试数量。在 WHR（${{P}}{{INT}}$ = 3.2 $\times{{10}}^{-{55}}$）和 WC（${{P}}_{{INT}}$ = 2.3$\times{{10}}^{-{41}}$）中发现了最显著的 G $\times$ S 证据。作为对其他特征的新型 G$\times$S 研究，我们发现常染色体遗传效应在女性中比男性弱，例如低密度脂蛋白胆固醇（LDL-C）、尿酸（UA）以及与糖尿病相关的特征，如空腹血糖和糖化血红蛋白。对于 LDL-C 和 UA，G$\times$S 的证据在年龄小于 50 岁的受试者中尤为显著，在这些受试者中，雌激素可以起到减弱这两个特征的常染色体遗传效应的作用。由于激素环境和特定的社会角色，男性和女性的环境背景存在系统性差异，这可能导致尽管具有相同的 DNA 材料，但基因表达也不同。由于许多环境暴露因素难以收集和量化，因此性别可以作为这些因素的良好替代指标。
