Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes for CVD risk traits
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.
This is the latest version of this eprint.
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.
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|Item Type:||Journal Article|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Gene Expression (incl. Microarray and other genome-wide approaches) (060405)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Quantitative Genetics (incl. Disease and Trait Mapping Genetics (060412)
|Divisions:||Current > Institutes > Institute of Health and Biomedical Innovation|
|Copyright Owner:||Copyright 2013 Elsevier|
|Copyright Statement:||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|
|Deposited On:||01 Jul 2014 22:58|
|Last Modified:||27 Mar 2016 19:40|
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Mapping eQTLs in the Norfolk Island genetic isolate
identifies candidate genes for CVD risk traits. (deposited 26 Mar 2014 00:37)
- Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes for CVD risk traits. (deposited 01 Jul 2014 22:58) [Currently Displayed]
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