Your height affects your health: genetic determinants and health-related outcomes in Taiwan
Jian‐Shiun Chiou, Chi‐Fung Cheng, Wen‐Miin Liang, Chen-Hsing Chou, Chung‐Hsing Wang, Wei‐De Lin, Mu-Lin Chiu, Wei‐Chung Cheng, Cheng‐Wen Lin, Ting‐Hsu Lin, Chiu‐Chu Liao, Shao‐Mei Huang, Chang‐Hai Tsai, Ying-Ju Lin, Fuu‐Jen Tsai
Abstract
Abstract Background Height is an important anthropometric measurement and is associated with many health-related outcomes. Genome-wide association studies (GWASs) have identified hundreds of genetic loci associated with height, mainly in individuals of European ancestry. Methods We performed genome-wide association analyses and replicated previously reported GWAS-determined single nucleotide polymorphisms (SNPs) in the Taiwanese Han population (Taiwan Biobank; n = 67,452). A genetic instrument composed of 251 SNPs was selected from our GWAS, based on height and replication results as the best-fit polygenic risk score (PRS), in accordance with the clumping and p -value threshold method. We also examined the association between genetically determined height (PRS 251 ) and measured height (phenotype). We performed observational (phenotype) and genetic PRS 251 association analyses of height and health-related outcomes. Results GWAS identified 6843 SNPs in 89 genomic regions with genome-wide significance, including 18 novel loci. These were the most strongly associated genetic loci ( EFEMP1 , DIS3L2 , ZBTB38 , LCORL , HMGA1 , CS , and GDF5 ) previously reported to play a role in height. There was a positive association between PRS 251 and measured height ( p < 0.001). Of the 14 traits and 49 diseases analyzed, we observed significant associations of measured and genetically determined height with only eight traits ( p < 0.05/[14 + 49]). Height was positively associated with body weight, waist circumference, and hip circumference but negatively associated with body mass index, waist-hip ratio, body fat, total cholesterol, and low-density lipoprotein cholesterol ( p < 0.05/[14 + 49]). Conclusions This study contributes to the understanding of the genetic features of height and health-related outcomes in individuals of Han Chinese ancestry in Taiwan.