title: Admixture mapping in two Mexican samples identifies significant associations of locus ancestry with triglyceride levels in the BUD13/ZNF259/APOA5 region and fine mapping points to rs964184 as the main driver of the association signal.
abstract: We carried out an admixture mapping study of lipid traits in two samples from Mexico City. Native American locus ancestry was significantly associated with triglyceride levels in a broad region of chromosome 11 overlapping the BUD13, ZNF259 and APOA5 genes. In our fine-mapping analysis of this region using dense genome-wide data, rs964184 is the only marker included in the 99% credible set of SNPs, providing strong support for rs964184 as the causal variant within this region. The frequency of the allele associated with increased triglyceride concentrations (rs964184-G) is between 30-40% higher in Native American populations from Mexico than in European populations. The evidence currently available for this variant indicates that it may be exerting its effect through three potential mechanisms: 1) modification of enhancer activity, 2) regulation of the expression of several genes in cis and/or trans, or 3) modification of the methylation patterns of the promoter of the APOA5 gene.
authors.affiliation: Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada.
authors.forename: Esteban J
authors.identifier: http://orcid.org/0000-0002-2057-8577
authors.initials: EJ
authors.lastname: Parra
authors.affiliation: Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mazurek
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, United States of America.
authors.forename: Christopher R
authors.identifier: http://orcid.org/0000-0001-9728-6567
authors.initials: CR
authors.lastname: Gignoux
authors.affiliation: School of Medicine, Stanford University, Stanford, CA, United States of America.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sockell
authors.affiliation: Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0003-3096-089X
authors.initials: M
authors.lastname: Agostino
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.affiliation: Department of Epidemiology, Human Genetics & Environmental Sciences, University of Texas School of Public Health, Houston, TX, United States of America.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Petty
authors.affiliation: Department of Epidemiology, Human Genetics & Environmental Sciences, University of Texas School of Public Health, Houston, TX, United States of America.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Hanis
authors.affiliation: Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, United States of America.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.affiliation: Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
authors.forename: Adan
authors.identifier: http://orcid.org/0000-0002-3182-3857
authors.initials: A
authors.lastname: Valladares-Salgado
authors.affiliation: Department of Epidemiology, Human Genetics & Environmental Sciences, University of Texas School of Public Health, Houston, TX, United States of America.
authors.forename: Jennifer E
authors.identifier: http://orcid.org/0000-0002-6372-6402
authors.initials: JE
authors.lastname: Below
authors.affiliation: Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Cruz
mesh_terms: D000328:Adult; D000483:Alleles; D000072040:Apolipoprotein A-V / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins; D017058:Mexican Americans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*; D044465:White People
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; C000595434:BUD13 homolog protein, human; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D016601:RNA-Binding Proteins; D014280:Triglycerides; C099746:ZPR1 protein, human