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Meta-analysis of genome-wide scans for hypertension and blood pressure in Caucasians shows evidence of susceptibility regions on chromosomes 2 and 3.

Koivukoski, Liisa; Fisher, Sheila A.; Kanninen, Timo; Lewis, Cathryn M.; Wowern, Fredrik LU ; Hunt, Steven; Kardia, Sharon L.R.; Levy, Daniel; Perola, Markus and Rankinen, Tuomo, et al. (2004) In Human Molecular Genetics 13(19). p.2325-2332
Abstract
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 (P-U) or with (P-W) a study sample size weighting... (More)
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 (P-U) or with (P-W) a study sample size weighting factor. Chromosome 3p14.1-q12.3 showed consistent evidence of linkage to HT (P-U=0.0001 and P-W=0.0001), diastolic BP (DBP) (P-U=0.007 and P-W=0.02), HT and DBP pooled (P-U=0.00002 and P-W=0.0001) and HT and systolic BP (SBP) pooled (P-U=0.0003 and P-W=0.0005). Chromosome 2p12-q22.1 showed evidence of linkage to HT (P-U=0.003 and P-W=0.009), DBP (P-U=0.05 and P-W=NS), HT and DBP pooled (P-U=0.001 and P-W=0.004) and HT and SBP pooled (P-U=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. (Less)
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Human Molecular Genetics
volume
13
issue
19
pages
2325 - 2332
publisher
Oxford University Press
external identifiers
  • wos:000223941500014
  • pmid:15294874
  • scopus:5444222846
ISSN
0964-6906
DOI
10.1093/hmg/ddh237
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English
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66b19ecc-ea8c-4fc4-bd3a-e46a4c0eda12 (old id 126835)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15294874&dopt=Abstract
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@article{66b19ecc-ea8c-4fc4-bd3a-e46a4c0eda12,
  abstract     = {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 (P-U) or with (P-W) a study sample size weighting factor. Chromosome 3p14.1-q12.3 showed consistent evidence of linkage to HT (P-U=0.0001 and P-W=0.0001), diastolic BP (DBP) (P-U=0.007 and P-W=0.02), HT and DBP pooled (P-U=0.00002 and P-W=0.0001) and HT and systolic BP (SBP) pooled (P-U=0.0003 and P-W=0.0005). Chromosome 2p12-q22.1 showed evidence of linkage to HT (P-U=0.003 and P-W=0.009), DBP (P-U=0.05 and P-W=NS), HT and DBP pooled (P-U=0.001 and P-W=0.004) and HT and SBP pooled (P-U=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.},
  author       = {Koivukoski, Liisa and Fisher, Sheila A. and Kanninen, Timo and Lewis, Cathryn M. and Wowern, Fredrik and Hunt, Steven and Kardia, Sharon L.R. and Levy, Daniel and Perola, Markus and Rankinen, Tuomo and Rao, Dabeeru C. and Rice, Treva and Thiel, Bonnie A. and Melander, Olle},
  issn         = {0964-6906},
  language     = {eng},
  number       = {19},
  pages        = {2325--2332},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Meta-analysis of genome-wide scans for hypertension and blood pressure in Caucasians shows evidence of susceptibility regions on chromosomes 2 and 3.},
  url          = {http://dx.doi.org/10.1093/hmg/ddh237},
  volume       = {13},
  year         = {2004},
}