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A large-scale exome array analysis of venous thromboembolism.

TitleA large-scale exome array analysis of venous thromboembolism.
Publication TypeJournal Article
Year of Publication2019
AuthorsLindström S, Brody JA, Turman C, Germain M, Bartz TM, Smith EN, Chen M-H, Puurunen M, Chasman D, Hassler J, Pankratz N, Basu S, Guan W, Gyorgy B, Ibrahim M, Empana J-P, Olaso R, Jackson R, Braekkan SK, McKnight B, Deleuze J-F, O'Donnell CJ, Jouven X, Frazer KA, Psaty BM, Wiggins KL, Taylor K, Reiner AP, Heckbert SR, Kooperberg C, Ridker P, Hansen J-B, Tang W, Johnson AD, Morange P-E, Trégouët DA, Kraft P, Smith NL
Secondary AuthorsKabrhel C
Corporate AuthorsINVENT Consortium
JournalGenet Epidemiol
Volume43
Issue4
Pagination449-457
Date Published2019 06
ISSN1098-2272
KeywordsAfrican Americans, Alleles, Case-Control Studies, Exome, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, High-Throughput Nucleotide Sequencing, Humans, Male, Microarray Analysis, Odds Ratio, Polymorphism, Single Nucleotide, Sample Size, Venous Thromboembolism
Abstract

Although recent Genome-Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome-wide search for low-frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta-analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct single variant and gene-based rare variant tests. In the single variant analysis, we limited our analysis to the 64,794 variants with at least 40 minor alleles across studies (minor allele frequency [MAF] ~0.08%). We confirmed associations with previously identified VTE loci, including ABO, F5, F11, and FGA. After adjusting for multiple testing, we observed no novel significant findings in single variant or gene-based analysis. Given our sample size, we had greater than 80% power to detect minimum odds ratios greater than 1.5 and 1.8 for a single variant with MAF of 0.01 and 0.005, respectively. Larger studies and sequence data may be needed to identify novel low-frequency and rare variants associated with VTE risk.

DOI10.1002/gepi.22187
Alternate JournalGenet Epidemiol
PubMed ID30659681
PubMed Central IDPMC6520188
Grant ListR01 HL120393 / HL / NHLBI NIH HHS / United States
HHSN268201600002C / HL / NHLBI NIH HHS / United States
R01 HL068639 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL060739 / HB / NHLBI NIH HHS / United States
R01 HL034594 / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01 CA050385 / CA / NCI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
R01 HL095080 / HL / NHLBI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
R01 CA067262 / CA / NCI NIH HHS / United States
HHSN268201600018C / HL / 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
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 HL116854 / HL / NHLBI NIH HHS / United States
P01 CA055075 / CA / NCI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
R01 HL085251 / 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
N01HC85086 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201700002C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201600003C / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201600004C / HL / NHLBI NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
HHSN268201600001C / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
R01 HL080467 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
R01 HL043201 / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 HL035464 / HL / NHLBI NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
R01 HL088521 / HL / NHLBI NIH HHS / United States
R01 CA049449 / CA / NCI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL073410 / HL / NHLBI NIH HHS / United States
RC1 HL099355 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States