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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.
de Las Fuentes, Lisa; Sung, Yun Ju; Noordam, Raymond; Winkler, Thomas; Feitosa, Mary F; Schwander, Karen; Bentley, Amy R; Brown, Michael R; Guo, Xiuqing; Manning, Alisa; Chasman, Daniel I; Aschard, Hugues; Bartz, Traci M; Bielak, Lawrence F; Campbell, Archie; Cheng, Ching-Yu; Dorajoo, Rajkumar; Hartwig, Fernando P; Horimoto, A R V R; Li, Changwei; Li-Gao, Ruifang; Liu, Yongmei; Marten, Jonathan; Musani, Solomon K; Ntalla, Ioanna; Rankinen, Tuomo; Richard, Melissa; Sim, Xueling; Smith, Albert V; Tajuddin, Salman M; Tayo, Bamidele O; Vojinovic, Dina; Warren, Helen R; Xuan, Deng; Alver, Maris; Boissel, Mathilde; Chai, Jin-Fang; Chen, Xu; Christensen, Kaare; Divers, Jasmin; Evangelou, Evangelos; Gao, Chuan; Girotto, Giorgia; Harris, Sarah E; He, Meian; Hsu, Fang-Chi; Kühnel, Brigitte; Laguzzi, Federica; Li, Xiaoyin; Lyytikäinen, Leo-Pekka.
Affiliation
  • de Las Fuentes L; Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO, 63110, USA. lfuentes@wustl.edu.
  • Sung YJ; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, 63110, USA. lfuentes@wustl.edu.
  • Noordam R; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, 63110, USA. yunju@wustl.edu.
  • Winkler T; Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, 2333ZA, The Netherlands.
  • Feitosa MF; Department of Genetic Epidemiology, University of Regensburg, 93051, Regensburg, Germany.
  • Schwander K; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63108, USA.
  • Bentley AR; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Brown MR; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Guo X; 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, 77030, USA.
  • Manning A; The Institute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
  • Chasman DI; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Aschard H; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
  • Bartz TM; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
  • Bielak LF; Harvard Medical School, Boston, MA, 02115, USA.
  • Campbell A; Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA.
  • Cheng CY; Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, 75724, France.
  • Dorajoo R; Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, WA, 98101, USA.
  • Hartwig FP; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Horimoto ARVR; Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Li C; Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Ecy Centre, Singapore, 169856, Singapore.
  • Li-Gao R; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 169857, Singapore.
  • Liu Y; Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, 138672, Singapore.
  • Marten J; Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, RS, 96020-220, Brazil.
  • Musani SK; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, UK.
  • Ntalla I; Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP, 5403000, Brazil.
  • Rankinen T; Epidemiology and Biostatistics, University of Georgia at Athens College of Public Health, Athens, GA, 30602, USA.
  • Richard M; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333ZA, Netherlands.
  • Sim X; Public Health Sciences, Epidemiology and Prevention, Wake Forest University Health Sciences, Winston-Salem, NC, 27157, USA.
  • Smith AV; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Tajuddin SM; Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39213, USA.
  • Tayo BO; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
  • Vojinovic D; Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
  • Warren HR; Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 70808, USA.
  • Xuan D; Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
  • Alver M; Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Boissel M; Icelandic Heart Association, Kopavogur, 201, Iceland.
  • Chai JF; Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
  • Chen X; Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, 60153, USA.
  • Christensen K; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Divers J; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
  • Evangelou E; NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, London, EC1M 6BQ, UK.
  • Gao C; Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
  • Girotto G; Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 51010, Estonia.
  • Harris SE; Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, 51010, Estonia.
  • He M; CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, 59000, France.
  • Hsu FC; Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
  • Kühnel B; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, 17177, Sweden.
  • Laguzzi F; Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, Southern Denmark University, Odense, 5000, Denmark.
  • Li X; Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Lyytikäinen LP; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, W2 1PG, UK.
Mol Psychiatry ; 26(6): 2111-2125, 2021 06.
Article in En | MEDLINE | ID: mdl-32372009
ABSTRACT
Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genome-Wide Association Study / Hypertension Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Mol Psychiatry Journal subject: BIOLOGIA MOLECULAR / PSIQUIATRIA Year: 2021 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genome-Wide Association Study / Hypertension Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Mol Psychiatry Journal subject: BIOLOGIA MOLECULAR / PSIQUIATRIA Year: 2021 Document type: Article Affiliation country: Estados Unidos