Causal effect of familial short stature on three quantitative traits in Taiwan

Objectives: With the accumulation of genetic basis for familial (genetic) short stature (FSS), the genetic association of FSS with health-related outcomes remains to be elucidated. In this study, we aimed to investigate the FSS genetic architecture and its causal effect on three quantitative traits in Taiwan.
Methods: We conducted an FSS genome-wide association study (GWAS) analysis (1,640 FSS cases and 22,372 controls). We performed a GWAS meta-analysis for the Taiwanese meta-height from the Taiwan Biobank (TWB)_height (N = 67,452) and the China Medical University Hospital (CMUH)_height GWAS summary statistics (N = 88,854). We calculated three polygenic risk scores (PRSs) of SNPs (P < 5 x 10-8) for FSS and Taiwanese meta-height with/without FSS, respectively. We explored the associations between three PRSs and the measured height, respectively. We also performed Mendelian randomization (MR) analysis for the causal effect of FSS and Taiwanese meta-height with/without FSS, on anthrop...

研究目的：随着家族性（遗传性）身材矮小（familial short stature, FSS）遗传基础研究的积累，其与健康相关结局的遗传关联仍有待阐明。本研究旨在探究家族性身材矮小的遗传架构，及其在中国台湾人群中对三种数量性状的因果效应。
研究方法：我们开展了一项家族性身材矮小的全基因组关联研究（genome-wide association study, GWAS）分析，纳入1,640例FSS病例与22,372例对照。我们针对台湾生物库（Taiwan Biobank, TWB）身高数据（N = 67,452）与中国医药大学附属医院（China Medical University Hospital, CMUH）身高GWAS汇总统计量（N = 88,854）的台湾人群身高数据进行了GWAS元分析。我们分别针对FSS以及伴/不伴FSS的台湾人群汇总身高，计算了单核苷酸多态性（single nucleotide polymorphism, SNPs）的三种多基因风险评分（polygenic risk scores, PRSs），其P值阈值设定为<5×10^-8。我们分别探究了三种多基因风险评分与实测身高之间的关联。此外，我们还开展了孟德尔随机化（Mendelian randomization, MR）分析，以评估FSS以及伴/不伴FSS的台湾人群汇总身高对人体测量学……