Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese

Circ Cardiovasc Genet. 2013 Dec;6(6):598-607. doi: 10.1161/CIRCGENETICS.113.000307. Epub 2013 Oct 28.

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.

Keywords: blood pressure; genomics; potassium; sodium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • Adult
  • Alleles
  • Asians / genetics
  • Blood Pressure / genetics*
  • China
  • F-Box Proteins / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Hypertension / ethnology
  • Hypertension / genetics
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Potassium, Dietary / administration & dosage
  • Pregnancy Proteins / genetics
  • Protein-Arginine N-Methyltransferases / genetics
  • Sodium, Dietary / administration & dosage
  • Suppressor Factors, Immunologic / genetics
  • TRPM Cation Channels / genetics
  • Transcription Factors / genetics

Substances

  • CDCA7 protein, human
  • F-Box Proteins
  • Nuclear Proteins
  • PIBF1 protein, human
  • Potassium, Dietary
  • Pregnancy Proteins
  • SALL1 protein, human
  • Sodium, Dietary
  • Suppressor Factors, Immunologic
  • TRPM Cation Channels
  • TRPM8 protein, human
  • Transcription Factors
  • PRMT6 protein, human
  • Protein-Arginine N-Methyltransferases
  • ADP-Ribosylation Factors
  • ARL4C protein, human