Genome-wide linkage analysis of carotid artery lumen diameter: the strong heart family study

Abstract

Background: A significant proportion of the variability in carotid artery lumen diameter is attributable to genetic factors.

Methods: Carotid ultrasonography and genotyping were performed in the 3300 American Indian participants in the Strong Heart Family Study (SHFS) to identify chromosomal regions harboring novel genes associated with inter-individual variation in carotid artery lumen diameter. Genome-wide linkage analysis was conducted using standard variance component linkage methods, implemented in SOLAR, based on multipoint identity-by-descent matrices.

Results: Genome-wide linkage analysis revealed a significant evidence for linkage for a locus for left carotid artery diastolic and systolic lumen diameters in Arizona SHFS participants on chromosome 7 at 120 cM (lod = 4.85 and 3.77, respectively, after sex and age adjustment, and lod = 3.12 and 2.72, respectively, after adjustment for sex, age, height, weight, systolic and diastolic blood pressure, diabetes mellitus and current smoking). Other regions with suggestive evidence of linkage for left carotid artery diastolic and systolic lumen diameter were found on chromosome 12 at 153 cM (lod = 2.20 and 2.60, respectively, after sex and age adjustment, and lod = 2.44 and 2.16, respectively, after full covariate adjustment) in Oklahoma SHFS participants; suggestive linkage for right carotid artery diastolic and systolic lumen diameter was found on chromosome 9 at 154 cM (lod = 2.72 and 3.19, respectively after sex and age adjustment, and lod = 2.36 and 2.21, respectively, after full covariate adjustment) in Oklahoma SHFS participants.

Conclusion: We found significant evidence for loci influencing carotid artery lumen diameter on chromosome 7q and suggestive linkage on chromosomes 12q and 9q.

Keywords: Carotid artery; Genetics; Linkage analysis; Ultrasonography; Variance components.

Figure 1. Genome-wide linkage results for LeftDD in different field centers

Chromosomes are oriented vertically and identified by the number on top. Hatch marks indicate the positions of genotyped marker loci. The scale of the genetic map is given on the left. The lod score scale is indicated below the chromosomes giving the highest genome-wide LOD scores. Blue: AZ; red: OK; green: DK; black: all; grey: all, allowing for inter-center heterogeneity (see text for details on the two different analyses on the entire sample).

Figure 2

Linkage results on different carotid artery diameter measures for chromosome 7 in AZ. The positions of genotyped marker loci are indicated on top. Blue: LeftDD, red: LeftSD, green: RightDD; black: RightSD;, grey: AvDD; yellow: AvSD