This article is part of the supplement: Genetic Analysis Workshop 13: Analysis of Longitudinal Family Data for Complex Diseases and Related Risk Factors .

Proceedings

Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study

Rector Arya¹ , Donna Lehman¹ , Kelly J Hunt¹ , Jennifer Schneider² , Laura Almasy² , John Blangero² , Michael P Stern¹ and Ravindranath Duggirala²

¹  Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA

²  Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA

author email corresponding author email

BMC Genetics 2003, 4(Suppl 1):S52doi:10.1186/1471-2156-4-S1-S52

Published:	31 December 2003

Abstract

Background

Epidemiological studies have indicated that obesity and low high-density lipoprotein (HDL) levels are strong cardiovascular risk factors, and that these traits are inversely correlated. Despite the belief that these traits are correlated in part due to pleiotropy, knowledge on specific genes commonly affecting obesity and dyslipidemia is very limited. To address this issue, we first conducted univariate multipoint linkage analysis for body mass index (BMI) and HDL-C to identify loci influencing variation in these phenotypes using Framingham Heart Study data relating to 1702 subjects distributed across 330 pedigrees. Subsequently, we performed bivariate multipoint linkage analysis to detect common loci influencing covariation between these two traits.

Results

We scanned the genome and identified a major locus near marker D6S1009 influencing variation in BMI (LOD = 3.9) using the program SOLAR. We also identified a major locus for HDL-C near marker D2S1334 on chromosome 2 (LOD = 3.5) and another region near marker D6S1009 on chromosome 6 with suggestive evidence for linkage (LOD = 2.7). Since these two phenotypes have been independently mapped to the same region on chromosome 6q, we used the bivariate multipoint linkage approach using SOLAR. The bivariate linkage analysis of BMI and HDL-C implicated the genetic region near marker D6S1009 as harboring a major gene commonly influencing these phenotypes (bivariate LOD = 6.2; LOD_eq = 5.5) and appears to improve power to map the correlated traits to a region, precisely.

Conclusions

We found substantial evidence for a quantitative trait locus with pleiotropic effects, which appears to influence both BMI and HDL-C phenotypes in the Framingham data.