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Nat Commun. 2019 Sep 27;10(1):4393. doi: 10.1038/s41467-019-12276-5.

Characterizing rare and low-frequency height-associated variants in the Japanese population.

Author information

1
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
2
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
3
Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
4
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
5
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
6
Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
7
Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
8
Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan.
9
Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.
10
Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, 565-8565, Japan.
11
Department of Biomedical Informatics, Harvard Medical School, Boston, MA02115, USA.
12
Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan.
13
Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan.
14
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
15
Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
16
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, 104-0045, Japan.
17
Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, 028-3694, Japan.
18
Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, Iwate, 028-3694, Japan.
19
Tohoku Medical Megabank Organization, Tohoku University, Sendai, 980-8573, Japan.
20
Graduate School of Medicine, Tohoku University, Sendai, 980-8575, Japan.
21
Center for Public Health Sciences, National Cancer Center, Tokyo, 104-0045, Japan.
22
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.
23
Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, 565-0871, Japan.
24
Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
25
RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
26
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan. yoichiro.kamatani@riken.jp.
27
Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan. yoichiro.kamatani@riken.jp.
28
Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan. yoichiro.kamatani@riken.jp.

Abstract

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.

PMID:
31562340
PMCID:
PMC6764965
DOI:
10.1038/s41467-019-12276-5
[Indexed for MEDLINE]
Free PMC Article

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