Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes for CVD risk traits


Autoria(s): Benton, Miles C.; Lea, Rod A.; Macartney-Coxson, Donia; Carless, Melanie A.; Göring, Harald H.; Bellis, Claire; Hanna, Michelle; Eccles, David; Chambers, Geoffrey K.; Curran, Joanne E.; Harper, Jacquie L.; Blangero, John; Griffiths, Lyn R.
Data(s)

05/12/2013

Resumo

Cardiovascular disease (CVD) affects millions of people worldwide and is influenced by numerous factors, including lifestyle and genetics. Expression quantitative trait loci (eQTLs) influence gene expression and are good candidates for CVD risk. Founder-effect pedigrees can provide additional power to map genes associated with disease risk. Therefore, we identified eQTLs in the genetic isolate of Norfolk Island (NI) and tested for associations between these and CVD risk factors. We measured genome-wide transcript levels of blood lymphocytes in 330 individuals and used pedigree-based heritability analysis to identify heritable transcripts. eQTLs were identified by genome-wide association testing of these transcripts. Testing for association between CVD risk factors (i.e., blood lipids, blood pressure, and body fat indices) and eQTLs revealed 1,712 heritable transcripts (p < 0.05) with heritability values ranging from 0.18 to 0.84. From these, we identified 200 cis-acting and 70 trans-acting eQTLs (p < 1.84 × 10(-7)) An eQTL-centric analysis of CVD risk traits revealed multiple associations, including 12 previously associated with CVD-related traits. Trait versus eQTL regression modeling identified four CVD risk candidates (NAAA, PAPSS1, NME1, and PRDX1), all of which have known biological roles in disease. In addition, we implicated several genes previously associated with CVD risk traits, including MTHFR and FN3KRP. We have successfully identified a panel of eQTLs in the NI pedigree and used this to implicate several genes in CVD risk. Future studies are required for further assessing the functional importance of these eQTLs and whether the findings here also relate to outbred populations.

Formato

application/pdf

Identificador

http://eprints.qut.edu.au/73161/

Publicador

Cell Press

Relação

http://eprints.qut.edu.au/73161/4/73161.pdf

DOI:10.1016/j.ajhg.2013.11.004

Benton, Miles C., Lea, Rod A., Macartney-Coxson, Donia, Carless, Melanie A., Göring, Harald H., Bellis, Claire, Hanna, Michelle, Eccles, David, Chambers, Geoffrey K., Curran, Joanne E., Harper, Jacquie L., Blangero, John, & Griffiths, Lyn R. (2013) Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes for CVD risk traits. The American Journal of Human Genetics, 93(6), pp. 1087-1099.

Direitos

Copyright 2013 Elsevier

This is the author’s version of a work that was accepted for publication in The American Journal of Human Genetics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in The American Journal of Human Genetics, [VOL 93, ISSUE 6, (2013)] DOI: 10.1016/j.ajhg.2013.11.004

Fonte

Institute of Health and Biomedical Innovation

Palavras-Chave #060400 GENETICS #060405 Gene Expression (incl. Microarray and other genome-wide approaches) #060412 Quantitative Genetics (incl. Disease and Trait Mapping Genetics
Tipo

Journal Article