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(Hypertension. 2007;50:557.)
© 2007 American Heart Association, Inc.

Original Articles

Genome-Wide Scans Meta-Analysis for Pulse Pressure

Elias Zintzaras; Georgios Kitsios; David Kent; Nicola J. Camp; Larry Atwood; Paul N. Hopkins; Steven C. Hunt

From the Center for Clinical Evidence Synthesis (E.Z.) and Center for Cardiovascular Health Services Research (D.K.), Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Biomathematics (E.Z., G.K.), University of Thessaly School of Medicine, Larissa, Greece; Division of Genetic Epidemiology, Department of Biomedical Informatics (N.J.C.), and Cardiovascular Genetics Division, Department of Internal Medicine (P.N.H., S.C.H.), University of Utah School of Medicine, Salt Lake City; and the Division of Epidemiology (L.A.), University of Minnesota, Minneapolis.

Correspondence to Elias Zintzaras, Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts University School of Medicine, Tufts-New England Medical Center, 750 Washington St, Tufts-NEMC #63, Boston, MA 02111. E-mail ezintzaras{at}nemc-tufts.org

Genome scans for identifying susceptibility loci for pulse pressure have produced inconclusive results. A heterogeneity-based genome search meta-analysis was applied to available genome-scan data on pulse pressure. A genome search meta-analysis divides the whole genome into 120 bins and identifies bins that rank high on average in terms of linkage statistics across genome scans unweighted or weighted by study size. The significance of each bin’s average rank (right-sided test) and heterogeneity among studies (left-sided test) was calculated using a Monte Carlo test. The meta-analysis involved 7 genome scans, 3 consisting of subjects of European descent. Of the 120 bins, 5 bins had significant average rank (P_rank0.05) by either unweighted or weighted analyses, 4 of which (bins 21.2: 21q22.11 to 21q22.3, 18.3: 18q12.2 to 18q21.33, 18.4: 18q21.33 to 18q23, and 6.2: 6p22.3 to 6p21.1) were significant by both. In subjects of European descent, 3 bins (22.1: 22q11.1 to 22q12.3, 22.2: 22q12.3 to 22q13.3, 10.4: 10q22.1 to 10q23.32) had P_rank0.05 with both unweighted and weighted analyses. Bin 10.4 showed low heterogeneity (P_Q=0.04). None of the bins showed low heterogeneity (P_Q>0.05), indicating variation in the strength of association. Further investigation of these regions may help to direct the identification of candidate genes for pulse pressure variation.

Key Words: genome search • meta-analysis • heterogeneity • HEGESMA • pulse pressure

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