Genome-Wide Haplotypic Testing in a Finnish Cohort Identifies a Novel Association with Low-Density Lipoprotein Cholesterol

• Activity Number: 353
• Type: Contributed
• Date/Time: Tuesday, August 11, 2015 : 10:30 AM to 12:20 PM
• Sponsor: WNAR
• Author(s): Qian Zhang* and Sharon Browning and Brian Browning
• Companies: University of Washington and University of Washington and University of Washington
• Keywords: Haplotype ; genome-wide association study ; cohort study ; LDL 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 x 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.