Systematic, genome-wide, sex-specific linkage of cardiovascular traits in French Canadians. Hypertension 2008 Apr;51(4):1156-62
Date
02/09/2008Pubmed ID
18259002DOI
10.1161/HYPERTENSIONAHA.107.105247Scopus ID
2-s2.0-40849142430 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
The sexual dimorphism of cardiovascular traits, as well as susceptibility to a variety of related diseases, has long been recognized, yet their sex-specific genomic determinants are largely unknown. We systematically assessed the sex-specific heritability and linkage of 539 hemodynamic, metabolic, anthropometric, and humoral traits in 120 French-Canadian families from the Saguenay-Lac-St-Jean region of Quebec, Canada. We performed multipoint linkage analysis using microsatellite markers followed by peak-wide linkage scan based on Affymetrix Human Mapping 50K Array Xba240 single nucleotide polymorphism genotypes in 3 settings, including the entire sample and then separately in men and women. Nearly one half of the traits were age and sex independent, one quarter were both age and sex dependent, and one eighth were exclusively age or sex dependent. Sex-specific phenotypes are most frequent in heart rate and blood pressure categories, whereas sex- and age-independent determinants are predominant among humoral and biochemical parameters. Twenty sex-specific loci passing multiple testing criteria were corroborated by 2-point single nucleotide polymorphism linkage. Several resting systolic blood pressure measurements showed significant genotype-by-sex interaction, eg, male-specific locus at chromosome 12 (male-female logarithm of odds difference: 4.16; interaction P=0.0002), which was undetectable in the entire population, even after adjustment for sex. Detailed interrogation of this locus revealed a 220-kb block overlapping parts of TAO-kinase 3 and SUDS3 genes. In summary, a large number of complex cardiovascular traits display significant sexual dimorphism, for which we have demonstrated genomic determinants at the haplotype level. Many of these would have been missed in a traditional, sex-adjusted setting.
Author List
Seda O, Tremblay J, Gaudet D, Brunelle PL, Gurau A, Merlo E, Pilote L, Orlov SN, Boulva F, Petrovich M, Kotchen TA, Cowley AW Jr, Hamet PAuthor
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cardiovascular DiseasesChromosomes, Human, Pair 12
Female
Genetic Predisposition to Disease
Genomics
Haplotypes
Humans
Linkage Disequilibrium
Lod Score
Male
Microsatellite Repeats
Phenotype
Polymorphism, Single Nucleotide
Quebec
Sex Characteristics
Sex Distribution
