Background Associations of adult height with cardiometabolic and pulmonary traits have been studied in majority European ancestry populations using Mendelian randomization and polygenic risk score (PRS) analysis. The standard PRS approach entails creating a PRS for height using variants identified in prior genome-wide association studies (GWAS). It is unclear how well the standard PRS approach performs in non-European populations and whether height-trait associations observed in Europeans are also observed in other populations. Methods In the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we used: (i) the standard approach to create a PRS for height (PRS1) and (ii) a novel approach to optimize the selection of variants from previously established height association loci to better explain height in HCHS/SOL (PRS2). We also estimated the extent to which PRS-trait associations were independent or mediated by the PRS effect on height. Results In 7539 women and 5245 men, PRS1 and PRS2 explained 9 and 29% of the variance in measured height, respectively. Both PRS1 and PRS2 were associated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/ FVC ratio, total cholesterol and 2-hour oral glucose-tolerance test insulin levels. Additionally, PRS2 was associated with estimated glomerular filtration rate and ankle brachial index. Both PRS1 and PRS2 had pleiotropic associations with FEV1/ FVC ratio in mediation analyses. Conclusions Associations of polygenic scores of height with measures of lung function and cholesterol were consistent with those observed in prior studies of majority European ancestry populations. Mediation analysis may augment standard PRS approaches to disentangle pleiotropic and mediated effects.

中文翻译：

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西班牙裔社区健康研究/拉丁裔研究中身高的遗传决定因素与心脏代谢和肺部特征的关系。

背景已使用孟德尔随机化和多基因风险评分（PRS）分析在大多数欧洲血统人群中研究了成年人身高与心脏代谢和肺部特征的关联。标准的PRS方法需要使用先前在全基因组关联研究（GWAS）中确定的变体来创建高度的PRS。目前尚不清楚标准的PRS方法在非欧洲人群中的表现如何，以及在其他人群中是否也观察到了欧洲人中观察到的身高关联。方法在拉美裔西班牙裔社区健康研究/研究（HCHS / SOL）中，我们使用了：（i）创建身高PRS的标准方法（PRS1），以及（ii）优化先前选择的变体的新颖方法建立了身高关联基因座，以更好地解释HCHS / SOL（PRS2）中的身高。我们还估计了PRS-性状关联独立或受PRS对身高的影响介导的程度。结果在7539名女性和5245名男性中，PRS1和PRS2分别解释了测量身高差异的9％和29％。PRS1和PRS2均与1秒内的强制呼气量（FEV1），强制肺活量（FVC），FEV1 / FVC比，总胆固醇和2小时口服葡萄糖耐量测试胰岛素水平相关。此外，PRS2与估计的肾小球滤过率和踝臂指数相关。在调解分析中，PRS1和PRS2都与FEV1 / FVC比具有多效性关联。结论身高多基因评分与肺功能和胆固醇水平的相关性与多数欧洲血统人群先前的研究一致。