title: Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs.
abstract: We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci.
authors.affiliation: Division of epidemiology, Human Genetics &Environmental Sciences, University of Texas School of Public Health, Houston, Texas, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Below
authors.affiliation: Department of Anthropology, University of Toronto at Mississauga, Mississauga, Ontario, Canada.
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Parra
authors.affiliation: Section of Genetic Medicine, Department of Medicine, University of Chicago, Illinois, USA.|Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN.|Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gamazon
authors.affiliation: Section of Genetic Medicine, Department of Medicine, University of Chicago, Illinois, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Torres
authors.affiliation: Department of Anthropology, University of Toronto at Mississauga, Mississauga, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Krithika
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Candille
authors.affiliation: The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.|The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Yingchang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichakul
authors.affiliation: Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Peralta-Romero
authors.affiliation: Department of Genetics and Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Department of Genetics and Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.affiliation: The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Omri
authors.initials: O
authors.lastname: Gottesman
authors.affiliation: The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Erwin
authors.initials: E
authors.lastname: Bottinger
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Xin-Qun
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Institute of Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor/UCLA Medical Center, Torrance, California, USA.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.affiliation: Institute of Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor/UCLA Medical Center, Torrance, California, USA.
authors.forename: Y-D
authors.initials: YD
authors.lastname: Ida Chen
authors.affiliation: Institute of Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor/UCLA Medical Center, Torrance, California, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.|The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.affiliation: Section of Genetic Medicine, Department of Medicine, University of Chicago, Illinois, USA.|Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN.
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: Miguel
authors.initials: M
authors.lastname: Cruz
authors.affiliation: Division of epidemiology, Human Genetics &Environmental Sciences, University of Texas School of Public Health, Houston, Texas, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Hanis
authors.affiliation: Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
authors.forename: Adan
authors.initials: A
authors.lastname: Valladares-Salgado
mesh_terms: D056726:Genetic Association Studies; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008800:Mexico; D009928:Organ Specificity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D044465:White People / Q000235:genetics
chemical_list: D008055:Lipids