Unknown

Dataset Information

0

A genome-wide association study for venous thromboembolism: the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.


ABSTRACT: 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.

SUBMITTER: Tang W 

PROVIDER: S-EPMC3990406 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

A genome-wide association study for venous thromboembolism: the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.

Tang Weihong W   Teichert Martina M   Chasman Daniel I DI   Heit John A JA   Morange Pierre-Emmanuel PE   Li Guo G   Pankratz Nathan N   Leebeek Frank W FW   Paré Guillaume G   de Andrade Mariza M   Tzourio Christophe C   Psaty Bruce M BM   Basu Saonli S   Ruiter Rikje R   Rose Lynda L   Armasu Sebastian M SM   Lumley Thomas T   Heckbert Susan R SR   Uitterlinden André G AG   Lathrop Mark M   Rice Kenneth M KM   Cushman Mary M   Hofman Albert A   Lambert Jean-Charles JC   Glazer Nicole L NL   Pankow James S JS   Witteman Jacqueline C JC   Amouyel Philippe P   Bis Joshua C JC   Bovill Edwin G EG   Kong Xiaoxiao X   Tracy Russell P RP   Boerwinkle Eric E   Rotter Jerome I JI   Trégouët David-Alexandre DA   Loth Daan W DW   Stricker Bruno H Ch BHC   Ridker Paul M PM   Folsom Aaron R AR   Smith Nicholas L NL  

Genetic epidemiology 20130505 5


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 GWA  ...[more]

Similar Datasets

| S-EPMC2875693 | biostudies-literature
| S-EPMC4136502 | biostudies-literature
| S-EPMC4176824 | biostudies-literature
| S-EPMC4177904 | biostudies-literature
| S-EPMC7665790 | biostudies-literature
| S-EPMC4112104 | biostudies-literature
| S-EPMC4135723 | biostudies-literature
| S-EPMC6263170 | biostudies-literature
| S-EPMC4069013 | biostudies-literature