201. Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese
- Author
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Qi Zhao, C. Charles Gu, Chung Shiuan Chen, Karen Schwander, Tanika N. Kelly, Jing Chen, Dabeeru C. Rao, Jichun Chen, Dongfeng Gu, Shengxu Li, Xu Ji, Xigui Wu, Jianxin Li, Jie Cao, Fanghong Lu, Renping Wang, Cashell E. Jaquish, Shufeng Chen, De-Pei Liu, Laiyuan Wang, Jixiang Ma, Jianfeng Huang, L. Lee Hamm, Lawrence C. Shimmin, Dongshuang Guo, Hongfan Li, Treva Rice, Jinjin Shen, Hao Mei, Jiang He, Yun Ju Sung, Jianjun Mu, James E. Hixson, Chong Shen, Xiangfeng Lu, and Dongsheng Hu
- Subjects
Adult ,Male ,Han chinese ,China ,Protein-Arginine N-Methyltransferases ,Genotype ,Psychological intervention ,TRPM Cation Channels ,Genomics ,Genome-wide association study ,Blood Pressure ,Biology ,Pregnancy Proteins ,Polymorphism, Single Nucleotide ,Article ,Dietary Sodium ,Asian People ,Gene Frequency ,Genetics ,Odds Ratio ,Suppressor Factors, Immunologic ,Humans ,Genetic Predisposition to Disease ,Genetics (clinical) ,Alleles ,ADP-Ribosylation Factors ,F-Box Proteins ,Cold pressor test ,Genetic variants ,Nuclear Proteins ,Potassium, Dietary ,Sodium, Dietary ,Middle Aged ,Blood pressure ,Hypertension ,Female ,Cardiology and Cardiovascular Medicine ,Genome-Wide Association Study ,Transcription Factors - Abstract
Background— Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals’ BP responses to dietary intervention and cold pressor test. Methods and Results— We conducted a genome-wide association study of BP responses in 1881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/d), a 7-day high-sodium (307.8 mmol/d), and a 7-day high-sodium plus potassium supplementation (60 mmol/d). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified 8 novel loci for BP phenotypes, which physically mapped in or near PRMT6 ( P =7.29×10 –9 ), CDCA7 ( P =3.57×10 –8 ), PIBF1 ( P =1.78×10 –9 ), ARL4C ( P =1.86×10 –8 ), IRAK1BP1 ( P =1.44×10 −10 ), SALL1 ( P =7.01×10 –13 ), TRPM8 ( P =2.68×10 –8 ), and FBXL13 ( P =3.74×10 –9 ). There was a strong dose–response relationship between the number of risk alleles of these independent single-nucleotide polymorphisms and the risk of developing hypertension during the 7.5-year follow-up in the study participants. Compared with those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third, and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively ( P =0.0003 for trend). Conclusions— Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and cold pressor test. The effect size of these novel loci on BP phenotypes is much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline.
- Published
- 2013