Publication Date:
2011-11-18
Description:
Abstract 710 Next-generation DNA sequencing is opening new avenues for genetic association studies in complex diseases that, like deep vein thrombosis (DVT), have a strong genetic basis only partially accounted for by currently identified risk variants. Using next-generation DNA sequencing, we resequenced the entire protein-coding area and intron-exon boundaries of ≈200 hemostatic/pro-inflammatory genes (including all coagulation factor and anticoagulant protein genes) in 26 Italian individuals with idiopathic DVT of the lower limbs and 28 age-, gender- and ethnicity-matched healthy controls. In order to enrich for genetic component, DVT patients were selected from a cohort of 730 cases of idiopathic DVT referred to the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center (Milan, Italy) on the basis of the following criteria: (a) negative for anti-phospholipid autoantibodies, anticoagulant protein deficiencies, factor V Leiden and prothrombin G20210A, (b) age of onset 40X after duplicate read removal) the 700-kilobase target region. A total of 2351 single nucleotide variants (SNVs) and 121 short indels were identified. We developed a dedicated software in order to be able to run association analyses in our dataset using PLINK. A plain association analysis was used to compare the frequencies of common SNVs, whereas a gene-based analysis of restricted non-synonymous mutations was used to reveal potential associations of rare variants. Of 626 common SNVs tested for association, 32 SNVs from 13 genes were associated with p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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