Human height is a representative phenotype to elucidate genetic architecture. However, the majority of large studies have been performed in European population. To investigate the rare and low-frequency variants associated with height, we construct a reference panel (N = 3,541) for genotype imputation by integrating the whole-genome sequence data from 1,037 Japanese with that of the 1000 Genomes Project, and perform a genome-wide association study in 191,787 Japanese. We report 573 height-associated variants, including 22 rare and 42 low-frequency variants. These 64 variants explain 1.7% of the phenotypic variance. Furthermore, a gene-based analysis identifies two genes with multiple height-increasing rare and low-frequency nonsynonymous variants (SLC27A3 and CYP26B1; PSKAT-O < 2.5 × 10−6). Our analysis shows a general tendency of the effect sizes of rare variants towards increasing height, which is contrary to findings among Europeans, suggesting that height-associated rare variants are under different selection pressure in Japanese and European populations.
Masato Akiyama, Kazuyoshi Ishigaki, Saori Sakaue, Yukihide Momozawa, Momoko Horikoshi, Makoto Hirata, Koichi Matsuda, Shiro Ikegawa, Atsushi Takahashi, Masahiro Kanai, Sadao Suzuki, Daisuke Matsui, Mariko Naito, Taiki Yamaji, Motoki Iwasaki, Norie Sawada, Kozo Tanno, Makoto Sasaki, Atsushi Hozawa, Naoko Minegishi, Kenji Wakai, Shoichiro Tsugane, Atsushi Shimizu, Masayuki Yamamoto, Yukinori Okada, Yoshinori Murakami, Michiaki Kubo & Yoichiro Kamatani,"Characterizing rare and low-frequency height-associated variants in the Japanese population", Nature Communications,10.1038/s41467-019-12276-5