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Thromb Haemost 2014; 112(05): 1036-1043
DOI: 10.1160/th14-03-0275
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

A genomewide study of body mass index and its genetic correlation with thromboembolic risk

Results from the GAIT project
Juan Carlos Souto
1   Unitat d’Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
Geórgia Pena
2   Nursing School, Maternal-Child Nursing and Public Health Department of the Nursing School of the Universidade Federal de Minas Gerais. Belo Horizonte, Brazil
,
Andrey Ziyatdinov
3   Unit of Genomics of Complex Diseases, Sant Pau Institut of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
,
Alfonso Buil
4   Department of Genetics Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
,
Sonia López
3   Unit of Genomics of Complex Diseases, Sant Pau Institut of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
,
Jordi Fontcuberta
1   Unitat d’Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
José Manuel Soria
3   Unit of Genomics of Complex Diseases, Sant Pau Institut of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
› Author Affiliations Financial support: This study was supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Proc. nº 6110–13–4, Brazil. Spanish grants: FIS PI11/0184, FIS PI12/00612 and Red Investigación Cardiovascular RD12/0042/0032. And AGAUR 2009 SGR/1147 and AGAUR 2009 SGR/1240 from Generalitat de Catalunya.
Further Information

Publication History

Received: 26 March 2014

Accepted after major revision: 13 June 2014

Publication Date:
29 November 2017 (online)

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Summary

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.

Keywords

Body mass index - genetics - genetic linkage analysis - obesity - thrombosis

 

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