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Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci.
de Las Fuentes, Lisa; Schwander, Karen L; Brown, Michael R; Bentley, Amy R; Winkler, Thomas W; Sung, Yun Ju; Munroe, Patricia B; Miller, Clint L; Aschard, Hugo; Aslibekyan, Stella; Bartz, Traci M; Bielak, Lawrence F; Chai, Jin Fang; Cheng, Ching-Yu; Dorajoo, Rajkumar; Feitosa, Mary F; Guo, Xiuqing; Hartwig, Fernando P; Horimoto, Andrea; Kolcic, Ivana; Lim, Elise; Liu, Yongmei; Manning, Alisa K; Marten, Jonathan; Musani, Solomon K; Noordam, Raymond; Padmanabhan, Sandosh; Rankinen, Tuomo; Richard, Melissa A; Ridker, Paul M; Smith, Albert V; Vojinovic, Dina; Zonderman, Alan B; Alver, Maris; Boissel, Mathilde; Christensen, Kaare; Freedman, Barry I; Gao, Chuan; Giulianini, Franco; Harris, Sarah E; He, Meian; Hsu, Fang-Chi; Kühnel, Brigitte; Laguzzi, Federica; Li, Xiaoyin; Lyytikäinen, Leo-Pekka; Nolte, Ilja M; Poveda, Alaitz; Rauramaa, Rainer; Riaz, Muhammad.
Afiliação
  • de Las Fuentes L; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
  • Schwander KL; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States.
  • Brown MR; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States.
  • Bentley AR; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States.
  • Winkler TW; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, United States.
  • Sung YJ; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States.
  • Munroe PB; Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
  • Miller CL; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States.
  • Aschard H; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States.
  • Aslibekyan S; Clinical Pharmacology, Queen Mary University of London, London, United Kingdom.
  • Bartz TM; National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, United Kingdom.
  • Bielak LF; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, United States.
  • Chai JF; Biochemistry and Molecular Genetics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, United States.
  • Cheng CY; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, United States.
  • Dorajoo R; Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.
  • Feitosa MF; Département de Génomes et Génétique, Institut Pasteur de Lille, Université de Lille, Lille, France.
  • Guo X; School of Public Health, Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States.
  • Hartwig FP; Cardiovascular Health Research Unit, University of Washington, Seattle, WA, United States.
  • Horimoto A; Department of Biostatistics, University of Washington, Seattle, WA, United States.
  • Kolcic I; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States.
  • Lim E; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
  • Liu Y; Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
  • Manning AK; Ophthalmology and Visual Sciences Academic Clinical Program, Medical School, Duke-National University of Singapore, Singapore, Singapore.
  • Marten J; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
  • Musani SK; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States.
  • Noordam R; Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Los Angeles, CA, United States.
  • Padmanabhan S; Postgraduate Programme in Epidemiology, Faculty of Medicine, Federal University of Pelotas, Pelotas, RS, Brazil.
  • Rankinen T; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
  • Richard MA; Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of Sao Paulo Medical School, Sao Paulo, SP, Brazil.
  • Ridker PM; University of Split School of Medicine, Split, Croatia.
  • Smith AV; Algebra University College, Zagreb, Croatia.
  • Vojinovic D; Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States.
  • Zonderman AB; Division of Cardiology, Department of Medicine, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States.
  • Alver M; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, United States.
  • Boissel M; Department of Medicine, Harvard Medical School, Boston, MA, United States.
  • Christensen K; Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
  • Freedman BI; Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States.
  • Gao C; Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands.
  • Giulianini F; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
  • Harris SE; Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States.
  • He M; Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States.
  • Hsu FC; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States.
  • Kühnel B; Harvard Medical School, Boston, MA, United States.
  • Laguzzi F; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United States.
  • Li X; Icelandic Heart Association, Kopavogur, Iceland.
  • Lyytikäinen LP; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, Netherlands.
  • Nolte IM; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands.
  • Poveda A; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.
  • Rauramaa R; National Institutes of Health, Baltimore, MD, United States.
  • Riaz M; Estonian Genome Center, Insititute of Genomics, University of Tartu, Tartu, Estonia.
Front Genet ; 14: 1235337, 2023.
Article em En | MEDLINE | ID: mdl-38028628
ABSTRACT

Introduction:

Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes.

Methods:

A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals).

Results:

In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.

Discussion:

Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article