An investigation of genome-wide associations of hypertension with microsatellite markers in the family blood pressure program (FBPP).
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.
Gu
C Charles
CC
Division of Biostatistics, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8067, St Louis, MO 63110, USA. gc@wubios.wustl.edu
Hunt
Steven C
SC
Kardia
Sharon
S
Turner
Stephen T
ST
Chakravarti
Aravinda
A
Schork
Nicholas
N
Olshen
Richard
R
Curb
David
D
Jaquish
Cashell
C
Boerwinkle
Eric
E
Rao
D C
DC
D015992:Body Mass Index; D005260:Female; D008040:Genetic Linkage; D016678:Genome; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*