title: A genomewide study of body mass index and its genetic correlation with thromboembolic risk. Results from the GAIT project.
abstract: Thrombosis and obesity are complex epidemiologically associated diseases. The mechanism of this association is not yet understood. It was the objective of this study to identify genetic components of body mass index (BMI) and their possible role in the risk of thromboembolic disease. With the self-reported BMI of 397 individuals from 21 extended families enrolled in the GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project, we estimated the heritability of BMI and the genetic correlation with the risk of thrombosis. Subjects were genotyped for an autosomal genome-wide scan with 363 highly-informative DNA markers. Univariate and bivariate multipoint linkage analyses were performed. The heritability for BMI was 0.31 (p=2.9×10⁻⁵). Thromboembolic disease (including venous and arterial) and BMI had a significant genetic correlation (ρG=0.54, p=0.005). Two linkage signals for BMI were obtained, one at 13q34 (LOD=3.36, p=0.0004) and other at 2q34, highly suggestive of linkage (LOD=1.95). Bivariate linkage analysis with BMI and thrombosis risk also showed a significant signal at 13q34 (LOD=3), indicating that this locus influences at the same time normal variation in the BMI phenotype as well as susceptibility to thrombosis. In conclusion, BMI and thrombosis are genetically correlated. The locus 13q34, which showed pleiotropy with both phenotypes, contains two candidate genes, which may explain our linkage pleiotropic signal and deserve further investigation as possible risk factors for obesity and thrombosis.
authors.affiliation: Juan Carlos Souto, MD, PhD, Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167, 08025, Barcelona, Spain, Tel.: +34 93 5537151, Fax: +34 93 5537153, E-mail: jsouto@santpau.cat.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Souto
authors.forename: Geórgia
authors.initials: G
authors.lastname: Pena
authors.forename: Audrey
authors.initials: A
authors.lastname: Ziyatdinov
authors.forename: Alfonso
authors.initials: A
authors.lastname: Buil
authors.forename: Sonia
authors.initials: S
authors.lastname: López
authors.forename: Jordi
authors.initials: J
authors.lastname: Fontcuberta
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Soria
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D015897:Comorbidity; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects; D005192:Family Health; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D018570:Risk Assessment; D012907:Smoking / Q000453:epidemiology; D013030:Spain / Q000453:epidemiology; D013923:Thromboembolism / Q000453:epidemiology* / Q000235:genetics; D019851:Thrombophilia / Q000139:chemically induced / Q000453:epidemiology; D020246:Venous Thrombosis / Q000453:epidemiology / Q000235:genetics
chemical_list: D003278:Contraceptives, Oral, Hormonal
keywords: Body mass index; genetic linkage analysis; genetics; obesity; thrombosis