期刊
ANNALS OF HUMAN GENETICS
卷 75, 期 -, 页码 456-467出版社
WILEY
DOI: 10.1111/j.1469-1809.2011.00654.x
关键词
vWF levels; Human CVD BeadChip; VWF and ABO
资金
- The UCL Genetics Institute
- BHF [PG/07/133/24260, RG/08/008, SP/07/007/23671, FS/2005/125, PG/07/131/24254]
- National Heart Lung and Blood Institute (NHLBI) [HL36310]
- Medical Research Council (MRC)
- British Heart Foundation
- Department of Health
- National Institute on Aging, US, NIH [AG13196]
- Agency for Health Care Policy Research [HS06516]
- John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health
- UK Department of Health
- UK Medical Research Centre [G0600705]
- British Heart Foundation [PG97012, FS05/125. 1958BC]
- MRC [G0000934, G0601653]
- Wellcome Trust [068545/Z/02]
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases
- National Human Genome Research Institute
- National Institute of Child Health and Human Development
- Juvenile Diabetes Research Foundation International
- [U01 DK062418]
- MRC [G0601354, G0000934, G0600705, G0601653, G0902037] Funding Source: UKRI
- British Heart Foundation [RG/08/013/25942, SP/07/007/23671, RG/08/008/25291, RG/10/12/28456, RG/07/008/23674] Funding Source: researchfish
- Medical Research Council [G0902037, G8802774, G0601653, G19/35, G0000934, G0100222, G0600705, G0601354] Funding Source: researchfish
- National Institute for Health Research [PHCS/C4/4/016] Funding Source: researchfish
We have used the gene-centric Illumina HumanCVD BeadChip to identify common genetic determinants of Von Willebrand factor (vWF) levels in healthy men and women. The Whitehall II (WHII) study (n = 5592) and the British Women's Heart and Health Study (BWHHS) (n = 3445) were genotyped using the HumanCVD BeadChip. Replication was conducted in the British Regional Heart Study (n = 3897) and 1958 Birth Cohort (n = 5048). We identified 48 single nucleotide polymorphisms (SNPs) in four genes/regions associated with vWF at P < 10(-4). These included 19 SNPs at the ABO blood group locus with the lead variant being rs657152 (P = 9.7 x 10(-233)). The lead variant in the 24 VWF SNPs was rs1063856 (P = 2.3 x 10(-20)). SNPs at ESR1 (rs6909023) and NRG1(rst1685103) showed modest associations with vWF, but these were not confirmed in a meta-analysis. Using variable selection, five SNPs at the locus for ABO and two for VWF were found to have independent associations with vWF levels. After adjustment for age and gender, the selected ABO SNPs explained 15% and the VWF SNPs an additional 2% of the variance in vWF levels. Individuals at opposite tails of the additive seven SNP allele score exhibited substantial differences in vWF levels. These data demonstrate that multiple common alleles with small effects make, in combination, important contributions to individual differences in vWF levels.
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