Meta-analysis of genome-wide scans for hypertension and blood pressure in Caucasians shows evidence of susceptibility regions on chromosomes 2 and 3.
Individual genome-wide scans of blood pressure (BP) and hypertension (HT) have shown inconsistent results. The aim of this study was to investigate whether there was any consistent evidence of linkage across multiple studies with similar ethnicity. We applied the genome-search meta-analysis method (GSMA) to nine published genome-wide scans of BP (n = 5) and HT (n = 4) from Caucasian populations. For each study, the genome was divided into 120 bins and ranked according to the maximum evidence of linkage within each bin. The ranks were summed and averaged across studies and significance levels were estimated, on the basis of a distribution function of summed ranks or permutation tests without (PU) or with (PW) a study sample size weighting factor. Chromosome 3p14.1-q12.3 showed consistent evidence of linkage to HT (PU = 0.0001 and PW = 0.0001), diastolic BP (DBP) (PU = 0.007 and PW = 0.02), HT and DBP pooled (PU = 0.00002 and PW = 0.0001) and HT and systolic BP (SBP) pooled (PU = 0.0003 and PW = 0.0005). Chromosome 2p12-q22.1 showed evidence of linkage to HT (PU = 0.003 and PW = 0.009), DBP (PU = 0.05 and PW = NS), HT and DBP pooled (PU = 0.001 and PW = 0.004) and HT and SBP pooled (PU = 0.001 and P W = 0.005). The summed ranks of the HT analysis correlated significantly with those of the DBP (r = 0.20, P = 0.03) but not with those of the SBP. Both loci showed clustering of significant bins in the analysis of HT and DBP. We conclude that modest or non-significant linkage on chromosomes 3p14.1-q12.3 and 2p12-q22.1 in each individual study translates into genome-wide significant or highly suggestive linkages to HT and DBP in our GSMA analysis.
Department of Endocrinology, Malmö University Hospital, Lund University, SE 205 02 Malmö, Sweden.
Liisa
L
Koivukoski
Sheila A
SA
Fisher
Timo
T
Kanninen
Cathryn M
CM
Lewis
Fredrik
F
von Wowern
Steven
S
Hunt
Sharon L R
SL
Kardia
Daniel
D
Levy
Markus
M
Perola
Tuomo
T
Rankinen
Dabeeru C
DC
Rao
Treva
T
Rice
Bonnie A
BA
Thiel
Olle
O
Melander
D001794:Blood Pressure / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2; D002893:Chromosomes, Human, Pair 3; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D044465:White People / Q000235:genetics