东亚人群长期平均血压的全基因组关联研究荟萃分析
Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.
作者信息
Li Changwei, Kim Yun Kyoung, Dorajoo Rajkumar, Li Huaixing, Lee I-Te, Cheng Ching-Yu, He Meian, Sheu Wayne H-H, Guo Xiuqing, Ganesh Santhi K, He Jiang, Lee Juyoung, Liu Jianjun, Hu Yao, Rao Dabeeru C, Tsai Fuu-Jen, Koh Jia Yu, Hu Hua, Liang Kae-Woei, Palmas Walter, Hixson James E, Han Sohee, Teo Yik-Ying, Wang Yiqin, Chen Jing, Lu Chieh Hsiang, Zheng Yingfeng, Gui Lixuan, Lee Wen-Jane, Yao Jie, Gu Dongfeng, Han Bok-Ghee, Sim Xueling, Sun Liang, Zhao Jinying, Chen Chien-Hsiun, Kumari Neelam, He Yunfeng, Taylor Kent D, Raffel Leslie J, Moon Sanghoon, Rotter Jerome I, Ida Chen Yii-der, Wu Tangchun, Wong Tien Yin, Wu Jer-Yuarn, Lin Xu, Tai E-Shyong, Kim Bong-Jo, Kelly Tanika N
机构信息
From the Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (C.L., J.H., J.Z., T.N.K.); Center for Genome Science, Korea National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea (Y.K.K., J.L., S.H., B.-G.H., S.M., B.-J.K.); Genome Institute of Singapore, Agency for Science, Technology and Research (R.D., J.L., Y.-Y.T.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences (H.L., Y.H., Y.W., L.S., X.L.); National Yang-Ming University Hospital, Taipei, Taiwan (I-T.L.); National Yang-Ming University Hospital, Taipei, Taiwan; Singapore Eye Research Institute, Singapore National Eye Center (Y.C., Y.K., Y.Z., N.K., T.Y.W.); Duke-NUS Graduate Medical School, National University of Singapore, (Y.C., N.K., T.Y.W., E-S.T.); Department of Ophthalmology (Y.C., T.Y.W.), Department of Statistics and Applied Probability (Y.-Y.T.), Life Sciences Institute (Y.-Y.T.), NUS Graduate School for Integrative Science and Engineering (Y.-Y.T.), Department of Medicine, National University Health System, Singapore (E-S.T.); MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (M.H., H.H., L.G., Y.H., T.W.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taipei, Taiwan (I-T.L., W.H-h.S); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H-h.S., K.-W.L.); Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA (X.G., J.Y., K.D.T., J.I.R., Y.-d.I.C.); Division of Cardiovascular Medicine, Department of Internal Medicine, Department of Human Genetics, University of Michigan, Ann Arbor (S.K.G.); Department of Medicine, Tulane University School of Medicine, New Orleans, LA (J.H., J.C.); Saw Swee Hock School of Public Health, National University of Singapore and National University Health System (J.L., Y.-Y.T., X.S., E-S.T.); Division of Biostatistics, Washington University School of Medicine, St. Louis, MO (D.C.R.); Department of Medical Genetics (F.-J.T.) and School of Chinese Medicine (C.-H.C., J.-Y.W.), China Medical University Hospital, Taichung, Taiwan; Department of Medicine, Columbia University Medical Center, New York, NY (W.P.); Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston (J.E.H.); Department of Internal Medicine, Ditmanson Medical Foundation, Chiayi Christian Hospital, Taiwan (C.H.L.); Department of Business Administration, National Chung Cheng University, Chia-yi, Taiwan (C.H.L.); Department of Nursing, DaYeh University, Changhua, Taiwan (C.H.L.); Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan (W.-J.L.); State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (D.G.); National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (C.-H.C., J.-Y.W.); Department of Ophthalmology and Visual Science, Khoo Teck Puat Hospital, Singapore, Singapore (N.K.); Medical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (L.J.R.); and Department of Epidemiology and Biostatistics, University of Georgia at Athens, Athens (C.L.); Department of Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan (K.-W.L.).
出版信息
Circ Cardiovasc Genet. 2017 Apr;10(2):e001527. doi: 10.1161/CIRCGENETICS.116.001527.
BACKGROUND
Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP.
METHODS AND RESULTS
We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a <5.0×10 and 2.5×10, respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 =5.03×10, stage-2 =8.64×10, joint =2.63×10) and mean arterial pressure (stage-1 =3.59×10, stage-2 =2.35×10, joint =2.64×10). Three previously reported BP loci (, , and ) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of with LTA systolic BP (stage-1 =8.55×10, stage-2 =1.62×10, joint =3.28×10) and mean arterial pressure (stage-1 =9.19×10, stage-2 =9.69×10, joint =2.15×10) phenotypes. Fourteen genes (, , , , , , , , -, , , and at 10q24.32; at 12q21.33; and at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes (=1.27×10 and 3.30×10, respectively).
CONCLUSIONS
We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the locus for LTA BP among East Asians.
背景
对长期平均（LTA）血压（BP）表型进行全基因组单标记和基于基因的荟萃分析可能会揭示有关血压的新发现。
方法与结果
我们在18422名东亚参与者中进行了全基因组分析（第一阶段），随后对≤46629名欧洲血统参与者进行了重复研究（第二阶段）。在第一阶段和第二阶段数据的联合分析中，分别通过<5.0×10和2.5×10确定显著的单核苷酸多态性和基因。我们在10q24.32处鉴定出1个新变异体rs4919669，影响LTA收缩压（第一阶段=5.03×10，第二阶段=8.64×10，联合=2.63×10）和平均动脉压（第一阶段=3.59×10，第二阶段=2.35×10，联合=2.64×10）。还针对所有血压表型鉴定出3个先前报道的血压基因座（、和）。基于基因的分析首次提供了与LTA收缩压（第一阶段=8.55×10，第二阶段=1.62×10，联合=3.28×10）和平均动脉压（第一阶段=9.19×10，第二阶段=9.69×10，联合=2.15×10）表型关联的有力证据。还鉴定出14个先前全基因组关联研究荟萃分析所涉及的基因（、、、、、、、、 - 、、、以及位于10q24.32的；位于12q21.33的；以及位于11p15.1的）。在先前LTA血压全基因组关联研究荟萃分析所鉴定的基因座中，我们跨种族重复了位于2p23.3的标记rs1275988与LTA收缩压和平均动脉压表型的关联（分别为=1.27×10和3.30×10）。
结论
我们鉴定出1个新变异体和1个新基因，并首次提供了东亚人中该基因座与LTA血压相关性的直接证据。
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