title: A genome-wide linkage and association scan reveals novel loci for hypertension and blood pressure traits.
abstract: Hypertension is caused by the interaction of environmental and genetic factors. The condition which is very common, with about 18% of the adult Hong Kong Chinese population and over 50% of older individuals affected, is responsible for considerable morbidity and mortality. To identify genes influencing hypertension and blood pressure, we conducted a combined linkage and association study using over 500,000 single nucleotide polymorphisms (SNPs) genotyped in 328 individuals comprising 111 hypertensive probands and their siblings. Using a family-based association test, we found an association with SNPs on chromosome 5q31.1 (rs6596140; P<9 × 10(-8)) for hypertension. One candidate gene, PDC, was replicated, with rs3817586 on 1q31.1 attaining P = 2.5 × 10(-4) and 2.9 × 10(-5) in the within-family tests for DBP and MAP, respectively. We also identified regions of significant linkage for systolic and diastolic blood pressure on chromosomes 2q22 and 5p13, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P<7 × 10(-5)) for DBP. This is the first combined linkage and association study of hypertension and its related quantitative traits with Chinese ancestry. The associations reported here account for the action of common variants whereas the discovery of linkage regions may point to novel targets for rare variant screening.
authors.affiliation: The State Key Laboratory of Brain and Cognitive Sciences, Department of Psychiatry, The University of Hong Kong, Hong Kong, China.
authors.forename: Youling
authors.initials: Y
authors.lastname: Guo
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
authors.forename: Tanya
authors.initials: T
authors.lastname: Chu
authors.forename: Yu Jing
authors.initials: YJ
authors.lastname: Fang
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Gui
authors.forename: Clara S
authors.initials: CS
authors.lastname: Tang
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Yip
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.forename: Yoon-Mi
authors.initials: YM
authors.lastname: Hur
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Tai Hing
authors.initials: TH
authors.lastname: Lam
authors.forename: Neil G
authors.initials: NG
authors.lastname: Thomas
mesh_terms: D000328:Adult; D001794:Blood Pressure; D002874:Chromosome Mapping; D003971:Diastole; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D014644:Genetic Variation; D016678:Genome; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013599:Systole
chemical_list: D005819:Genetic Markers