Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study

• Published in: European journal of human genetics : EJHG Vol. 17; no. 12; pp. 1650 - 1657
• Main Authors: EHRET, Georg B, O'CONNOR, Ashley A, WEDER, Alan, COOPER, Richard S, CHAKRAVARTI, Aravinda
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-12-2009
• Subjects: Adolescent; Adult; African Americans; American Native Continental Ancestry Group - genetics; Antigens; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Cardiology. Vascular system; Cardiovascular disease; Cardiovascular diseases; Chromosome 1; Chromosomes; Chromosomes, Human, Pair 1 - genetics; Classical genetics, quantitative genetics, hybrids; European Continental Ancestry Group - genetics; Families & family life; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes; Genetic Linkage; Genetic Predisposition to Disease; Genetic variance; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Genomics; Haplotypes; Human; Humans; Hypertension; Hypertension - genetics; Male; Medical genetics; Medical sciences; Medicine; Middle Aged; Molecular and cellular biology; Mutation; Phenotype; Phenotypes; Pressure distribution; Quality Control; Quantitative trait loci; Quantitative Trait Loci - genetics; Single-nucleotide polymorphism; Statistics; Studies; Young Adult; United States > US; Baltimore Maryland; Genetic mapping; Hypertension; Cartography; Pathogenesis; Quantitative character; Chromosome A1; essential hypertension; Cardiovascular disease; Genetic determinism; Essential; Association; complex disease genetics; Follow up study; association mapping; Genetic linkage; Genetics; Peak; Severe; Complex syndrome
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/ejhg.2009.94

Essential hypertension is a major cardiovascular risk factor and a large proportion of this risk is genetic. Identification of genomic regions consistently associated with hypertension has been difficult in association studies to date as this requires large sample sizes.We previously published a large genome-wide linkage scan in Americans of African (AA) and European (EA) descent in the GenNet Network of the Family Blood Pressure Program (FBPP). A highly significant linkage peak was identified on chr1q spanning a region of 100 cM. In this study, we genotyped 1569 SNPs under this linkage peak in 2379 individuals to identify whether common genetic variants were associated with blood pressure (BP) at this locus.Our analysis, using two different family-based association tests, provides suggestive evidence (P< or =2 x 10(-5)) for a collection of single nucleotide polymorphisms (SNPs) associated with BP. In EAs, using diastolic BP as a quantitative phenotype, three variants located in or near the GPA33, CD247, and F5 genes, emerge as our top hits; for systolic BP, variants in GPA33, CD247, and REN are our best findings. No variant in AAs came close to suggestive evidence after multiple-test corrections (P> or =8 x 10(-5)). In summary, we show that systematic follow-up of a linkage signal can help discover candidate variants for essential hypertension that require a follow-up in yet larger samples. The failure to identify common variants is either because of low statistical power or the existence of rare coding variants in specific families or both, which require additional studies to clarify.