Human Genetics

, Volume 121, Issue 5, pp 577–590

An investigation of genome-wide associations of hypertension with microsatellite markers in the family blood pressure program (FBPP)

  • C. Charles Gu
  • Steven C. Hunt
  • Sharon Kardia
  • Stephen T. Turner
  • Aravinda Chakravarti
  • Nicholas Schork
  • Richard Olshen
  • David Curb
  • Cashell Jaquish
  • Eric Boerwinkle
  • D. C. Rao
Original Investigation

Abstract

The Family Blood Pressure Program (FBPP) has data on 387 microsatellite markers in 13,524 subjects from four major ethnic groups. We investigated genetic association with hypertension of the linkage markers. Family-based methods were used to test association of the 387 loci with resting blood pressures (BPs) [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and the hypertension status (HT). We applied a vote-counting approach to pool results across the three correlated traits, network samples, and ethnic groups to refine the selection of susceptibility loci. The association analyses captured signals missed by previous linkage scans. We found 71 loci associated with at least one of the three traits in at least one of the four ethnic groups at the significance level of 0.01. After validation across multiple samples and related traits, we identified by vote-counting 21 candidate loci for hypertension. Two loci, D3S2459 and D10S1412 confirmed findings in Network-specific linkage scans (GENOA and SAPPHIRe). Many of the candidate loci were reported by others in linkage to BPs, body weight, heart disease, and diabetes. We also observed frequent presence of quantitative trait loci (QTLs) involved in autoimmune and neurological disorders (e.g., NOD2). The vote-counting method of pooling results recognizes the potential that a gene may be involved in varying ways among different samples, which we believe is responsible for identifying genes in the less explored inflammatory pathways to hypertension.

Supplementary material

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • C. Charles Gu
    • 1
  • Steven C. Hunt
    • 3
  • Sharon Kardia
    • 4
  • Stephen T. Turner
    • 5
  • Aravinda Chakravarti
    • 6
  • Nicholas Schork
    • 7
  • Richard Olshen
    • 8
  • David Curb
    • 9
  • Cashell Jaquish
    • 10
  • Eric Boerwinkle
    • 11
  • D. C. Rao
    • 1
    • 2
  1. 1.Division of BiostatisticsWashington University School of MedicineSt LouisUSA
  2. 2.Departments of Genetics and PsychiatryWashington University School of MedicineSt LouisUSA
  3. 3.Cardiovascular GeneticsUniversity of Utah School of MedicineSalt Lake CityUSA
  4. 4.Department of EpidemiologyUniversity of Michigan School of Public HealthAnn ArborUSA
  5. 5.Mayo Clinic College of MedicineRochesterUSA
  6. 6.Institute of Genetic MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  7. 7.Polymorphism Research Laboratory, Department of PsychiatryUniversity of CaliforniaSan DiegoUSA
  8. 8.Health and Research PolicyStanford University School of MedicineStanfordUSA
  9. 9.Pacific Health Research InstituteHonoluluUSA
  10. 10.National Heart, Lung and Blood Institute (NHLBI)BethesdaUSA
  11. 11.Human Genetics CenterUniversity of Texas-Houston Health Science CenterHoustonUSA

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