Consortium

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• Alternative Title:
  Genet Epidemiol
• Personal Author:
  Tang, Weihong ; Teichert, Martina ; Chasman, Daniel I. ; Heit, John A. ; Morange, Pierre-Emmanuel ; Li, Guo ; Pankratz, Nathan ; Leebeek, Frank W. ; Paré, Guillaume ; de Andrade, Mariza ; Tzourio, Christophe ; Psaty, Bruce M. ; Basu, Saonli ; Ruiter, Rikje ; Rose, Lynda ; Armasu, Sebastian M. ; Lumley, Thomas ; Heckbert, Susan R. ; Uitterlinden, André G. ; Lathrop, Mark ; Rice, Kenneth M. ; Cushman, Mary ; Hofman, Albert ; Lambert, Jean-Charles ; Glazer, Nicole L. ; Pankow, James S. ; Witteman, Jacqueline C. ; Amouyel, Philippe ; Bis, Joshua C. ; Bovill, Edwin G. ; Kong, Xiaoxiao ; Tracy, Russell P. ; Boerwinkle, Eric ; Rotter, Jerome I. ; Trégouët, David-Alexandre ; Loth, Daan W. ; Stricker, Bruno H. Ch. ; Ridker, Paul M ; Folsom, Aaron R. ; Smith, Nicholas L.
• Description:
  Venous thromboembolism (VTE) is a common, heritable disease resulting in high rates of hospitalization and mortality. Yet few associations between VTE and genetic variants, all in the coagulation pathway, have been established. To identify additional genetic determinants of VTE, we conducted a two-stage genome-wide association study (GWAS) among individuals of European ancestry in the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) VTE consortium. The discovery GWAS comprised 1,618 incident VTE cases out of 44,499 participants from six community-based studies. Genotypes for genome-wide single-nucleotide polymorphisms (SNPs) were imputed to approximately 2.5 million SNPs in HapMap and association with VTE assessed using study-design appropriate regression methods. Meta-analysis of these results identified two known loci, in F5 and ABO. Top 1,047 tag SNPs (P ≤ 0.0016) from the discovery GWAS were tested for association in an additional 3,231 cases and 3,536 controls from three case-control studies. In the combined data from these two stages, additional genome-wide significant associations were observed on 4q35 at F11 (top SNP rs4253399, intronic to F11) and on 4q28 at FGG (rs6536024, 9.7 kb from FGG; P < 5.0 × 10(-13) for both). The associations at the FGG locus were not completely explained by previously reported variants. Loci at or near SUSD1 and OTUD7A showed borderline yet novel associations (P < 5.0 × 10(-6) ) and constitute new candidate genes. In conclusion, this large GWAS replicated key genetic associations in F5 and ABO, and confirmed the importance of F11 and FGG loci for VTE. Future studies are warranted to better characterize the associations with F11 and FGG and to replicate the new candidate associations.
• Subjects:
  Aged Aging Article Case-Control Studies Cohort Studies Female Genetic Epidemiology Genetics Genome-wide Association Genome-Wide Association Study Humans Male Meta-Analysis As Topic Middle Aged Polymorphism, Single Nucleotide Regression Analysis Risk Factors Venous Thromboembolism Venous Thrombosis

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• Source:
  Genet Epidemiol. 37(5):512-521
• Pubmed ID:
  23650146
• Pubmed Central ID:
  PMC3990406
• Document Type:
  Journal Article
• Funding:
  HHSN268201100012C/HL/NHLBI NIH HHS/United States ; HL073410/HL/NHLBI NIH HHS/United States ; U01 DD000235/DD/NCBDD CDC HHS/United States ; HHSN268201100009I/HL/NHLBI NIH HHS/United States ; R01 HL095080/HL/NHLBI NIH HHS/United States ; UL1TR000124/TR/NCATS NIH HHS/United States ; N01 HC085083/HC/WHI NIH HHS/United States ; HL95080/HL/NHLBI NIH HHS/United States ; R01 HL083141/HL/NHLBI NIH HHS/United States ; R01HL59367/HL/NHLBI NIH HHS/United States ; HHSN268201100010C/HL/NHLBI NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; R01 AG015928/AG/NIA NIH HHS/United States ; HHSN268201100008C/HL/NHLBI NIH HHS/United States ; U01 HL080295/HL/NHLBI NIH HHS/United States ; HHSN268201100005G/HL/NHLBI NIH HHS/United States ; N01 HC085086/HC/WHI NIH HHS/United States ; HHSN268201100008I/HL/NHLBI NIH HHS/United States ; HL085251/HL/NHLBI NIH HHS/United States ; N01-HC-85081/HC/NHLBI NIH HHS/United States ; R01 HL068986/HL/NHLBI NIH HHS/United States ; R01 HL043851/HL/NHLBI NIH HHS/United States ; R01 HL059367/HL/NHLBI NIH HHS/United States ; HHSN268201100007C/HL/NHLBI NIH HHS/United States ; HL105756/HL/NHLBI NIH HHS/United States ; R01 HL095603/HL/NHLBI NIH HHS/United States ; N01 HC015103/HC/NHLBI NIH HHS/United States ; R01 HL085251/HL/NHLBI NIH HHS/United States ; R01 HL066216/HL/NHLBI NIH HHS/United States ; HL043201/HL/NHLBI NIH HHS/United States ; R56 AG020098/AG/NIA NIH HHS/United States ; HHSN268201100011I/HL/NHLBI NIH HHS/United States ; HHSN268201100011C/HL/NHLBI NIH HHS/United States ; R01 HL086694/HL/NHLBI NIH HHS/United States ; N01 HC085085/HC/NHLBI NIH HHS/United States ; N01 HC075150/HC/WHI NIH HHS/United States ; R01 HL087652/HL/NHLBI NIH HHS/United States ; AG-20098/AG/NIA NIH HHS/United States ; U01 HG004402/HG/NHGRI NIH HHS/United States ; HL087652/HL/NHLBI NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; N01HC55222/HL/NHLBI NIH HHS/United States ; R01 HL074745/HL/NHLBI NIH HHS/United States ; N01-HC-85086/HC/NHLBI NIH HHS/United States ; HL068986/HL/NHLBI NIH HHS/United States ; N01HC85086/HL/NHLBI NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; U01HG004402/HG/NHGRI NIH HHS/United States ; AG-027058/AG/NIA NIH HHS/United States ; HL074745/HL/NHLBI NIH HHS/United States ; R01 HL060739/HB/NHLBI NIH HHS/United States ; N01-HC-85082/HC/NHLBI NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; HHSN268201100006C/HL/NHLBI NIH HHS/United States ; N01 HC-55222/HC/NHLBI NIH HHS/United States ; HHSN268201200036C/HL/NHLBI NIH HHS/United States ; R01HL087641/HL/NHLBI NIH HHS/United States ; HHSN268201100005I/HL/NHLBI NIH HHS/United States ; N01 HC085080/HC/WHI NIH HHS/United States ; N01-HC-85083/HC/NHLBI NIH HHS/United States ; N01-HC-75150/HC/NHLBI NIH HHS/United States ; N01-HC-85080/HC/NHLBI NIH HHS/United States ; R01 CA092153/CA/NCI NIH HHS/United States ; R01 HL080295/HL/NHLBI NIH HHS/United States ; HL060739/HL/NHLBI NIH HHS/United States ; N01 HC085079/HC/WHI NIH HHS/United States ; N01 HC085081/HC/WHI NIH HHS/United States ; R01 CA047988/CA/NCI NIH HHS/United States ; N01 HC085084/HC/NHLBI NIH HHS/United States ; R01 AG020098/AG/NIA NIH HHS/United States ; R01 HL080467/HL/NHLBI NIH HHS/United States ; N01HC85082/HL/NHLBI NIH HHS/United States ; N01HC75150/HL/NHLBI NIH HHS/United States ; R01 HL043201/HL/NHLBI NIH HHS/United States ; HHSN268201100009C/HL/NHLBI NIH HHS/United States ; R01 HL060739/HL/NHLBI NIH HHS/United States ; HHSN268201100005C/HL/NHLBI NIH HHS/United States ; U01 HG004735/HG/NHGRI NIH HHS/United States ; DK063491/DK/NIDDK NIH HHS/United States ; HHSN268201100007I/HL/NHLBI NIH HHS/United States ; N01-HC-85079/HC/NHLBI NIH HHS/United States ; HL080295/HL/NHLBI NIH HHS/United States ; N01-HC-85239/HC/NHLBI NIH HHS/United States ; AG-023629/AG/NIA NIH HHS/United States ; N01HC85079/HL/NHLBI NIH HHS/United States ; R01 AG023629/AG/NIA NIH HHS/United States ; R01 HL087641/HL/NHLBI NIH HHS/United States ; R01 HL073410/HL/NHLBI NIH HHS/United States ; R01 AG027058/AG/NIA NIH HHS/United States ; N01 HC045133/HC/NHLBI NIH HHS/United States ; N01HC85080/HL/NHLBI NIH HHS/United States ; N01 HC035129/HC/NHLBI NIH HHS/United States ; R56 AG023629/AG/NIA NIH HHS/United States ; R01HL086694/HL/NHLBI NIH HHS/United States
• Volume:
  37
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:6688fbbc1d4e4fd2d513948aa0e45f4f1cf49df4cca83ddcee3e7d9b585d9024
• Download URL:
  https://stacks.cdc.gov/view/cdc/41950/cdc_41950_DS1.pdf
• File Type:
  [PDF - 441.25 KB ]