title: Genome-wide haplotypic testing in a Finnish cohort identifies a novel association with low-density lipoprotein cholesterol.
abstract: We performed genome-wide tests for association between haplotype clusters and each of 9 metabolic traits in a cohort of 5402 Northern Finnish individuals genotyped for 330 000 single-nucleotide polymorphisms. The metabolic traits were body mass index, C-reactive protein, diastolic blood pressure, glucose, high-density lipoprotein (HDL), insulin, low-density lipoprotein (LDL), systolic blood pressure, and triglycerides. Haplotype clusters were determined using Beagle. There were LDL-associated clusters in the chromosome 4q13.3-q21.1 region containing the albumin (ALB) and platelet factor 4 (PF4) genes. This region has not been associated with LDL in previous genome-wide association studies. The most significant haplotype cluster in this region was associated with 0.488 mmol/l higher LDL (95% CI: 0.361-0.615 mmol/l, P-value: 6.4 × 10(-14)). We also observed three previously reported associations: Chromosome 16q13 with HDL, chromosome 1p32.3-p32.2 with LDL and chromosome 19q13.31-q13.32 with LDL. The chromosome 1 and chromosome 4 LDL associations do not reach genome-wide significance in single-marker analyses of these data, illustrating the power of haplotypic association testing.
authors.affiliation: 1] Department of Medicine, University of Washington, Seattle, WA, USA [2] Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Qian S
authors.initials: QS
authors.lastname: Zhang
authors.affiliation: 1] Department of Biostatistics, University of Washington, Seattle, WA, USA [2] Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Browning
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Browning
mesh_terms: D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood*; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D015331:Cohort Studies; D005260:Female; D005387:Finland; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable
chemical_list: D008078:Cholesterol, LDL