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Hum Mol Genet. 2015 Mar 15;24(6):1791-800. doi: 10.1093/hmg/ddu583. Epub 2014 Nov 26.

Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.

Author information

1
MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Hubei, Wuhan 430030, China, hemeian@hotmail.com.
2
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism and.
3
Vanderbilt Epidemiology Center, Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
4
Department of Endocrinology, The Central Hospital of Xuzhou, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu 221009, China.
5
Saw Swee Hock School of Public Health.
6
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do 363-700, Republic of Korea.
7
Laboratory for Medical Informatics.
8
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
9
Institute of Urology and Nephrology, First Affiliated Hospital & Center for Genomic and Personalized Medicine, Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, China.
10
Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
11
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
12
MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Hubei, Wuhan 430030, China.
13
Department of Nutrition and.
14
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore 168751.
15
Saw Swee Hock School of Public Health, Department of Ophthalmology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore 168751, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore 169857.
16
Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism and.
17
Department of Epidemiology, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
18
State Key Laboratory of Cardiovascular Disease, Department of Evidence Based Medicine, Fuwai Hospital, National Center of Cardiovascular Diseases.
19
Medical Scientific Research Center and.
20
Saw Swee Hock School of Public Health, Department of Ophthalmology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore 168751, Department of Ophthalmology, Erasmus Medical Center, Rotterdam 3015, The Netherlands, Memory Aging & Cognition Centre, National University Health System, Singapore, Singapore 119228.
21
Department of Preventive Medicine, Seoul National University, College of Medicine, Seoul 110-799, Republic of Korea.
22
Saw Swee Hock School of Public Health, Department of Ophthalmology, Department of Paediatrics National University Health Systems, Agency for Science, Technology and Research, Genome Institute of Singapore, Singapore, Singapore 138672.
23
Laboratory for Genotyping Development.
24
Office of Population Studies Foundation, University of San Carlos, Cebu City 6000, Philippines.
25
Department of Medicine, Yong Loo Lin School of Medicine.
26
Saw Swee Hock School of Public Health, Agency for Science, Technology and Research, Genome Institute of Singapore, Singapore, Singapore 138672.
27
Shanghai Municipal Center for Disease Control & Prevention, 1380 Zhong Shan Road (W), Shanghai 200336, China.
28
Laboratory for Statistical Analysis.
29
Department of Paediatrics National University Health Systems.
30
Saw Swee Hock School of Public Health, Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109-2029, USA.
31
State Key Laboratory of Medical Genomics, Molecular Medical Center, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
32
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
33
Laboratory for Cardiovascular Diseases, RIKEN Center for Genomic Medicine, Yokohama 230-0045, Japan.
34
Division of Cancer Epidemiology & Genetics, Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
35
State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
36
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
37
Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
38
Department of Cardiology, Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei 442008, China.
39
Institute of Urology and Nephrology, First Affiliated Hospital & Center for Genomic and Personalized Medicine.
40
Department of Genome Science, Aichi-Gakuin University, School of Dentistry, Nagoya 464-8650, Japan.
41
Duke-National University of Singapore Graduate Medical School, Singapore, Singapore 169857, Duke Eye Center, Duke University Medical Center, Durham, NC 27710, USA.
42
Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
43
Saw Swee Hock School of Public Health, NUS Graduate School for Integrative Science and Engineering, Life Sciences Institute, Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore 119077, Agency for Science, Technology and Research, Genome Institute of Singapore, Singapore, Singapore 138672.
44
Department of Ophthalmology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore 168751.
45
Saw Swee Hock School of Public Health, Department of Medicine, Yong Loo Lin School of Medicine, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore 169857.

Abstract

Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 × 10(-8), together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians.

PMID:
25429064
PMCID:
PMC4351379
DOI:
10.1093/hmg/ddu583
[Indexed for MEDLINE]
Free PMC Article

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