title: Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes for CVD risk traits.
abstract: 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.
authors: Genomics Research Centre, Griffith Health Institute, Griffith University, Southport, QLD 4222, Australia.
authors: Miles C
authors: MC
authors: Benton
authors: Rod A
authors: RA
authors: Lea
authors: Donia
authors: D
authors: Macartney-Coxson
authors: Melanie A
authors: MA
authors: Carless
authors: Harald H
authors: HH
authors: Göring
authors: Claire
authors: C
authors: Bellis
authors: Michelle
authors: M
authors: Hanna
authors: David
authors: D
authors: Eccles
authors: Geoffrey K
authors: GK
authors: Chambers
authors: Joanne E
authors: JE
authors: Curran
authors: Jacquie L
authors: JL
authors: Harper
authors: John
authors: J
authors: Blangero
authors: Lyn R
authors: LR
authors: Griffiths
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008542:Melanesia; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D060066:Protein Interaction Maps; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D014158:Transcription, Genetic