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Genetic determinants of plasma β 2 ‐glycoprotein  I levels: a genome‐wide association study in extended pedigrees from S pain
Author(s) -
Athanasiadis G.,
SabaterLleal M.,
Buil A.,
Souto J. C.,
Borrell M.,
Lathrop M.,
Watkins H.,
Almasy L.,
Hamsten A.,
Soria J. M.
Publication year - 2013
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12120
Subject(s) - genome wide association study , single nucleotide polymorphism , genetics , biology , genetic association , snp , heritability , pedigree chart , phenotype , gene , genetic variation , computational biology , bioinformatics , genotype
Summary Background β 2 ‐ G lycoprotein  I (β 2 ‐ GPI ), also designated apolipoprotein  H , is a 50‐k D a protein that circulates in blood at high concentrations, playing important roles in autoimmune diseases, hemostasis, atherogenesis, and angiogenesis, as well as in host defense against bacteria and in protein/cellular waste removal. Plasma β 2 ‐ GPI levels have a significant genetic component (heritability of ~ 80%). Objectives To present the results of a genome‐wide association study for plasma β 2 ‐ GPI levels in a set of extended pedigrees from the G enetic A nalysis of I diopathic T hrombophilia ( GAIT ) Project. Patients/Methods A total of 306 individuals for whom β 2 ‐ GPI plasma measurements were available were typed for 307 984 single‐nucleotide polymorphisms ( SNP s) with the Infinium 317k B eadchip ( I llumina). Association with the β 2 ‐ GPI phenotype was investigated through variance component analysis, and the most significant results were followed up for association with coronary artery disease ( CAD ) in an independent in silico analysis involving 5765 CAD cases from the PROCARDIS P roject and 7264 controls from the PROCARDIS Project and the W ellcome T rust C ase C ontrol C onsortium ( WTCCC ) collection. Results After correction for multiple testing, three SNP s located in/around two genes ( ELF 5 and SCUBE 2 ) reached genome‐wide significance. Moreover, an SNP in the APOH gene showed suggestive association with the β 2 ‐ GPI phenotype. Some of the identified genes are plausible biological candidates, as they are actually or potentially involved in inflammatory processes. Conclusions Our results represent a first step towards identifying common variants reflecting the genetic architecture influencing plasma β 2 ‐ GPI levels, and warrant further validation by functional experiments, as the functions of some of the discovered loci are still unknown.

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