Human Molecular Genetics Advance Access published online on August 4, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh237
© 2004 by Oxford University Press
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1 Department of Endocrinology, Malmö University Hospital, Lund University, Malmö, Sweden
* To whom correspondence should be addressed. E-mail: olle.melander{at}endo.mas.lu.se.
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, based on 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 PW=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 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 linkage to HT and DBP in our GSMA analysis.
Article
Meta-analysis of genome-wide scans for hypertension and blood pressure in Caucasians shows evidence of susceptibility regions on chromosomes 2 and 3
2 Guy's, King's and St Thomas' School of Medicine, King's College London, Division of Genetics and Development, London, UK
3 Biocomputing Platforms Ltd, Espoo, Finland
4 Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, Utah, USA
5 Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA
6 NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA
7 Department of Molecular Medicine, KTL, MOLS, Helsinki, Finland
8 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA
9 Division of Biostatistics and Departments of Genetics, Psychiatry, and Mathematics, Washington University in St. Louis, St. Louis, Missouri, USA
10 Division of Biostatistics, Washington University School of Medicine, St. Louis, Missousi, USA
11 Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA
12 Department of Endocrinology, Malmö University Hospital, Lund University, SE 205 02 Malmö, Sweden
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