title: Effects of copy number variable regions on local gene expression in white blood cells of Mexican Americans.
abstract: Only few systematic studies on the contribution of copy number variation to gene expression variation have been published to date. Here we identify effects of copy number variable regions (CNVRs) on nearby gene expression by investigating 909 CNVRs and expression levels of 12059 nearby genes in white blood cells from Mexican-American participants of the San Antonio Family Heart Study. We empirically evaluate our ability to detect the contribution of CNVs to proximal gene expression (presumably in cis) at various window sizes (up to a 10 Mb distance) between the gene and CNV. We found a ~1-Mb window size to be optimal for capturing cis effects of CNVs. Up to 10% of the CNVs in this study were found to be significantly associated with the expression of at least one gene within their vicinity. As expected, we find that CNVs that directly overlap gene sequences have the largest effects on gene expression (compared with non-overlapping CNVRs located nearby), with positive correlation (except for a few exceptions) between estimated genomic dosage and expression level. We find that genes whose expression level is significantly influenced by nearby CNVRs are enriched for immunity and autoimmunity related genes. These findings add to the currently limited catalog of CNVRs that are recognized as expression quantitative trait loci, and have implications for future study designs as well as for prioritizing candidate causal variants in genomic regions associated with disease.
authors.affiliation: 1] Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA [2] Department of Cellular and Structural Biology, UT Health Science Center San Antonio, San Antonio, TX, USA.
authors.forename: August
authors.initials: A
authors.lastname: Blackburn
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Marcio
authors.initials: M
authors.lastname: Almeida
authors.affiliation: Department of Computer Science, University of Texas San Antonio, San Antonio, TX, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Dean
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.affiliation: Centre for Genetic Origins of Health and Disease, University of Western Australia, Perth, WA, Australia.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.affiliation: Centre for Genetic Origins of Health and Disease, University of Western Australia, Perth, WA, Australia.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Abraham
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Mahaney
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Comuzzie
authors.affiliation: 1] Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA [2] Southwest National Primate Research Center, San Antonio, TX, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Williams-Blangero
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Department of Medicine/Division of Clinical Epidemiology, UT Health Science Center San Antonio, San Antonio, TX, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Lehman
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
mesh_terms: D015551:Autoimmunity / Q000235:genetics; D056915:DNA Copy Number Variations / Q000276:immunology*; D005190:Family; D005260:Female; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007162:Immunoproteins / Q000235:genetics*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D017058:Mexican Americans; D040641:Quantitative Trait Loci / Q000276:immunology*
chemical_list: D007162:Immunoproteins