TY - JOUR
T1 - Five blood pressure loci identified by an updated genome-wide linkage scan
T2 - Meta-analysis of the family blood pressure program
AU - Simino, Jeannette
AU - Shi, Gang
AU - Kume, Rezart
AU - Schwander, Karen
AU - Province, Michael A.
AU - Gu, C. Charles
AU - Kardia, Sharon
AU - Chakravarti, Aravinda
AU - Ehret, Georg
AU - Olshen, Richard A.
AU - Turner, Stephen T.
AU - Ho, Low Tone
AU - Zhu, Xiaofeng
AU - Jaquish, Cashell
AU - Paltoo, Dina
AU - Cooper, Richard S.
AU - Weder, Alan
AU - Curb, J. David
AU - Boerwinkle, Eric
AU - Hunt, Steven C.
AU - Rao, Dabeeru C.
N1 - Funding Information:
acknowledgment: We thank all the participants in GenNet, GENOa, hyperGEN, and SaPPhIRe. a complete list of FBPP investigators may be found at: http://www.biostat.wustl.edu/fbpp/acknowledgments.html. This research was partly supported by grants T32 hL091823, U01 hL54473, U10 hL054512, R01 hL086694, and R21 hL095054 from the National heart, Lung, and Blood Institute.
PY - 2011/3
Y1 - 2011/3
N2 - Background A preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension.MethodsWe performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226 African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican-American participants (total N = 13,044). Variance components models were fit to measured (raw) blood pressure levels and two types of antihypertensive medication adjusted blood pressure phenotypes within each of 10 subgroups defined by race and network. A modified Fisher's method was used to combine the P values for each linkage marker across the 10 subgroups.ResultsFive quantitative trait loci (QTLs) were detected on chromosomes 6p22.3, 8q23.1, 20q13.12, 21q21.1, and 21q21.3 based on significant linkage evidence (defined by logarithm of odds (lod) score 3) in at least one meta-analysis and lod scores 1 in at least 2 subgroups defined by network and race. The chromosome 8q23.1 locus was supported by Asian-, Caucasian-, and Mexican-American-specific meta-analyses. ConclusionsThe new QTLs reported justify new candidate gene studies. They may help support results from genome-wide association studies (GWAS) that fall in these QTL regions but fail to achieve the genome-wide significance.
AB - Background A preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension.MethodsWe performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226 African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican-American participants (total N = 13,044). Variance components models were fit to measured (raw) blood pressure levels and two types of antihypertensive medication adjusted blood pressure phenotypes within each of 10 subgroups defined by race and network. A modified Fisher's method was used to combine the P values for each linkage marker across the 10 subgroups.ResultsFive quantitative trait loci (QTLs) were detected on chromosomes 6p22.3, 8q23.1, 20q13.12, 21q21.1, and 21q21.3 based on significant linkage evidence (defined by logarithm of odds (lod) score 3) in at least one meta-analysis and lod scores 1 in at least 2 subgroups defined by network and race. The chromosome 8q23.1 locus was supported by Asian-, Caucasian-, and Mexican-American-specific meta-analyses. ConclusionsThe new QTLs reported justify new candidate gene studies. They may help support results from genome-wide association studies (GWAS) that fall in these QTL regions but fail to achieve the genome-wide significance.
KW - QTL
KW - blood pressure
KW - genetics
KW - hypertension
KW - linkage
KW - meta-analysis
UR - http://www.scopus.com/inward/record.url?scp=79951681492&partnerID=8YFLogxK
U2 - 10.1038/ajh.2010.238
DO - 10.1038/ajh.2010.238
M3 - Article
C2 - 21151011
AN - SCOPUS:79951681492
SN - 0895-7061
VL - 24
SP - 347
EP - 354
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 3
ER -