Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese.
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.
['He|Jiang|J|', 'Kelly|Tanika N|TN|', 'Zhao|Qi|Q|', 'Li|Hongfan|H|', 'Huang|Jianfeng|J|', 'Wang|Laiyuan|L|', 'Jaquish|Cashell E|CE|', 'Sung|Yun Ju|YJ|', 'Shimmin|Lawrence C|LC|', 'Lu|Fanghong|F|', 'Mu|Jianjun|J|', 'Hu|Dongsheng|D|', 'Ji|Xu|X|', 'Shen|Chong|C|', 'Guo|Dongshuang|D|', 'Ma|Jixiang|J|', 'Wang|Renping|R|', 'Shen|Jinjin|J|', 'Li|Shengxu|S|', 'Chen|Jing|J|', 'Mei|Hao|H|', 'Chen|Chung-Shiuan|CS|', 'Chen|Shufeng|S|', 'Chen|Jichun|J|', 'Li|Jianxin|J|', 'Cao|Jie|J|', 'Lu|Xiangfeng|X|', 'Wu|Xigui|X|', 'Rice|Treva K|TK|', 'Gu|C Charles|CC|', 'Schwander|Karen|K|', 'Hamm|L Lee|LL|', 'Liu|Depei|D|', 'Rao|Dabeeru C|DC|', 'Hixson|James E|JE|', 'Gu|Dongfeng|D|']
D020727:ADP-Ribosylation Factors D000328:Adult D000483:Alleles D044466:Asians D001794:Blood Pressure D002681:China D044783:F-Box Proteins D005260:Female D005787:Gene Frequency D020022:Genetic Predisposition to Disease D055106:Genome-Wide Association Study D005838:Genotype D006801:Humans D006973:Hypertension D008297:Male D008875:Middle Aged D009687:Nuclear Proteins D016017:Odds Ratio D020641:Polymorphism, Single Nucleotide D017419:Potassium, Dietary D011257:Pregnancy Proteins D011484:Protein-Arginine N-Methyltransferases D012982:Sodium, Dietary D013491:Suppressor Factors, Immunologic D050053:TRPM Cation Channels D014157:Transcription Factors
blood pressure sodium potassium genomics