title: Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese.
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.
  
  
  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.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.forename: Tanika N
authors.initials: TN
authors.lastname: Kelly
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Hongfan
authors.initials: H
authors.lastname: Li
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Huang
authors.forename: Laiyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Cashell E
authors.initials: CE
authors.lastname: Jaquish
authors.forename: Yun Ju
authors.initials: YJ
authors.lastname: Sung
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Shimmin
authors.forename: Fanghong
authors.initials: F
authors.lastname: Lu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Mu
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Hu
authors.forename: Xu
authors.initials: X
authors.lastname: Ji
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.forename: Dongshuang
authors.initials: D
authors.lastname: Guo
authors.forename: Jixiang
authors.initials: J
authors.lastname: Ma
authors.forename: Renping
authors.initials: R
authors.lastname: Wang
authors.forename: Jinjin
authors.initials: J
authors.lastname: Shen
authors.forename: Shengxu
authors.initials: S
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Mei
authors.forename: Chung-Shiuan
authors.initials: CS
authors.lastname: Chen
authors.forename: Shufeng
authors.initials: S
authors.lastname: Chen
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Lu
authors.forename: Xigui
authors.initials: X
authors.lastname: Wu
authors.forename: Treva K
authors.initials: TK
authors.lastname: Rice
authors.forename: C Charles
authors.initials: CC
authors.lastname: Gu
authors.forename: Karen
authors.initials: K
authors.lastname: Schwander
authors.forename: L Lee
authors.initials: LL
authors.lastname: Hamm
authors.forename: Depei
authors.initials: D
authors.lastname: Liu
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D002681:China; D044783:F-Box Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017419:Potassium, Dietary / Q000008:administration & dosage; D011257:Pregnancy Proteins / Q000235:genetics; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics; D012982:Sodium, Dietary / Q000008:administration & dosage; D013491:Suppressor Factors, Immunologic / Q000235:genetics; D050053:TRPM Cation Channels / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C445325:CDCA7 protein, human; D044783:F-Box Proteins; D009687:Nuclear Proteins; C110058:PIBF1 protein, human; D017419:Potassium, Dietary; D011257:Pregnancy Proteins; C104146:SALL1 protein, human; D012982:Sodium, Dietary; D013491:Suppressor Factors, Immunologic; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D014157:Transcription Factors; C447833:PRMT6 protein, human; D011484:Protein-Arginine N-Methyltransferases; D020727:ADP-Ribosylation Factors; C541133:ARL4C protein, human
keywords: blood pressure; genomics; potassium; sodium