In healthy adults, 70%–80% of our vital capacity can be exhaled in a single second when measured by spirometry. This is made possible by the combination of a highly elastic lung, a low-resistance airway tree and recruitable respiratory muscles. Reduced spirometric values do not necessarily indicate disease, however, since forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the ratio of FEV1/FVC all decrease as part of normal ageing. Much of lung function is determined by genetics: approximately 40% of lung function can be explained by familial heritability,1 and genome-wide association studies have identified hundreds of genetic variants associated with lung function that, when combined, account for around 6%–12% of this heritability.2 Understanding the genetic control of lung function can give vital insights into the nature of disease and ultimately help us develop preventative treatments. Mendelian randomisation (MR) is a statistical construct that exploits the relationship between genetic variants and biological features to identify causal associations. In what is known as instrumental variable analysis, the effect of a genetic variant on an exposure (eg, a blood protein) and an outcome (eg, a phenotype or disease) is used to determine the effect of the exposure on the outcome. The ‘randomisation’ element comes from the random allocation of alleles during meiosis: this allows comparison between two groups who differ only by the level of the exposure—akin to treatment arms in a randomised controlled trial—and hence a causal inference can be made. For an easy-to-understand description of …

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睾丸激素和肺功能：肺更大、衰退更慢还是两者兼而有之？

通过肺活量测定法测量，健康成年人可以在一秒钟内呼出 70%–80% 的肺活量。这是通过高弹性肺、低阻力气道树和可招募呼吸肌的结合来实现的。然而，肺活量降低并不一定表明患有疾病，因为作为正常衰老的一部分，1 秒用力呼气量 (FEV1)、用力肺活量 (FVC) 和 FEV1/FVC 比值都会下降。大部分肺功能是由遗传学决定的：大约 40% 的肺功能可以通过家族遗传性来解释，1 全基因组关联研究已经确定了数百种与肺功能相关的遗传变异，这些变异组合起来约占 6% – 12% 的遗传力。2 了解肺功能的基因控制可以为了解疾病的本质提供重要的见解，并最终帮助我们开发预防性治疗方法。孟德尔随机化 (MR) 是一种统计结构，利用遗传变异和生物学特征之间的关系来识别因果关联。在所谓的工具变量分析中，遗传变异对暴露（例如血液蛋白）和结果（例如表型或疾病）的影响被用来确定暴露对结果的影响。 “随机化”元素来自减数分裂期间等位基因的随机分配：这允许在仅暴露水平不同的两组之间进行比较（类似于随机对照试验中的治疗组），因此可以做出因果推断。为了易于理解的描述...