Multivariate linkage analysis of blood pressure and body mass index

Abstract

Multivariate linkage analyses of correlated traits provide greater statistical power to identify genetic loci with effects too small to be detected in single trait analyses. We conducted genomewide multivariate analyses of systolic BP, diastolic BP, and body mass index (BMI) in 1,848 non-Hispanic white subjects (968 females, 880 males) from 279 multigenerational pedigrees from Rochester, Minnesota. Blood pressure was measured by random zero sphygmomanometer; body mass index was calculated from measurements of height and weight; and genotypes were measured at 520 microsatellite marker loci distributed across the 22 autosomes. Univariate linkage analyses demonstrated tentative evidence of linkage (defined by univariate LOD scores of 1.30-1.99) for diastolic BP on chromosome 18 and for BMI on chromosomes 3, 10, and 18. Bivariate linkage analyses showed tentative evidence of linkage (defined by bivariate LOD scores of 2.06-2.86) for systolic and diastolic BP on chromosome 14 and for either measure of BP and BMI on chromosomes 2, 3, 10, and 18; and suggestive evidence of linkage (defined by bivariate LOD scores of 2.87-3.99) for either measure of BP and BMI on chromosomes 10 and chromosome 15. Trivariate linkage analyses of systolic and diastolic BP and BMI provided evidence of a region influencing all three traits on chromosome 10, where the trivariate LOD score rose to a maximum value of 4.09 (at 144 cM, P=0.0007), and possibly on chromosome 2, where it rose to a maximum value of 2.80 (at 77 cM, P=0.0075). For genomewide linkage analyses to succeed in localizing genes influencing BP, it may be advantageous to exploit the greater statistical power of multivariate linkage analyses to identify loci with pleiotropic effects on correlated traits.