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Sun D, Richard M, Musani SK, et al. Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits. HGG Adv. 2020;2(1)doi: 10.1016/j.xhgg.2020.100013.
Sun, D., Richard, M., Musani, S. K., Sung, Y. J., Winkler, T. W., Schwander, K., Chai, J. F., Guo, X., Kilpeläinen, T. O., Vojinovic, D., Aschard, H., Bartz, T. M., Bielak, L. F., Brown, M. R., Chitrala, K., Hartwig, F. P., Horimoto, A. R. V. R., Liu, Y., Manning, A. K., Noordam, R., Smith, A. V., Harris, S. E., Kühnel, B., Lyytikäinen, L. P., Nolte, I. M., Rauramaa, R., van der Most, P. J., Wang, R., Ware, E. B., Weiss, S., Wen, W., Yanek, L. R., Arking, D. E., Arnett, D. K., Barac, A., Boerwinkle, E., Broeckel, U., Chakravarti, A., Chen, Y. I., Cupples, L. A., Davigulus, M. L., de Las Fuentes, L., de Mutsert, R., de Vries, P. S., Delaney, J. A. C., Roux, A. V. D., Dörr, M., Faul, J. D., Fretts, A. M., Gallo, L. C., Grabe, H. J., Gu, C. C., Harris, T. B., Hartman, C. C. A., Heikkinen, S., Ikram, M. A., Isasi, C., Johnson, W. C., Jonas, J. B., Kaplan, R. C., Komulainen, P., Krieger, J. E., Levy, D., Liu, J., Lohman, K., Luik, A. I., Martin, L. W., Meitinger, T., Milaneschi, Y., O'Connell, J. R., Palmas, W. R., Peters, A., Peyser, P. A., Pulkki-Råback, L., Raffel, L. J., Reiner, A. P., Rice, K., Robinson, J. G., Rosendaal, F. R., Schmidt, C. O., Schreiner, P. J., Schwettmann, L., Shikany, J. M., Shu, X. O., Sidney, S., Sims, M., Smith, J. A., Sotoodehnia, N., Strauch, K., Tai, E. S., Taylor, K., Uitterlinden, A. G., van Duijn, C. M., Waldenberger, M., Wee, H. L., Wei, W. B., Wilson, G., Xuan, D., Yao, J., Zeng, D., Zhao, W., Zhu, X., Zonderman, A. B., Becker, D. M., Deary, I. J., Gieger, C., Lakka, T. A., Lehtimäki, T., North, K. E., Oldehinkel, A. J., Penninx, B. W. J. H., Snieder, H., Wang, Y. X., Weir, D. R., Zheng, W., Evans, M. K., Gauderman, W. J., Gudnason, V., Horta, B. L., Liu, C. T., Mook-Kanamori, D. O., Morrison, A. C., Pereira, A. C., Psaty, B. M., Amin, N., Fox, E. R., Kooperberg, C., Sim, X., Bierut, L., Rotter, J. I., Kardia, S. L. R., Franceschini, N., Rao, D. C., & Fornage, M. (2021). Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits. HGG advances, 2(1), . https://doi.org/10.1016/j.xhgg.2020.100013
Sun, Daokun, et al. "Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits." HGG advances vol. 2,1 (2021). doi: https://doi.org/10.1016/j.xhgg.2020.100013
Sun D, Richard M, Musani SK, Sung YJ, Winkler TW, Schwander K, Chai JF, Guo X, Kilpeläinen TO, Vojinovic D, Aschard H, Bartz TM, Bielak LF, Brown MR, Chitrala K, Hartwig FP, Horimoto ARVR, Liu Y, Manning AK, Noordam R, Smith AV, Harris SE, Kühnel B, Lyytikäinen LP, Nolte IM, Rauramaa R, van der Most PJ, Wang R, Ware EB, Weiss S, Wen W, Yanek LR, Arking DE, Arnett DK, Barac A, Boerwinkle E, Broeckel U, Chakravarti A, Chen YI, Cupples LA, Davigulus ML, de Las Fuentes L, de Mutsert R, de Vries PS, Delaney JAC, Roux AVD, Dörr M, Faul JD, Fretts AM, Gallo LC, Grabe HJ, Gu CC, Harris TB, Hartman CCA, Heikkinen S, Ikram MA, Isasi C, Johnson WC, Jonas JB, Kaplan RC, Komulainen P, Krieger JE, Levy D, Liu J, Lohman K, Luik AI, Martin LW, Meitinger T, Milaneschi Y, O'Connell JR, Palmas WR, Peters A, Peyser PA, Pulkki-Råback L, Raffel LJ, Reiner AP, Rice K, Robinson JG, Rosendaal FR, Schmidt CO, Schreiner PJ, Schwettmann L, Shikany JM, Shu XO, Sidney S, Sims M, Smith JA, Sotoodehnia N, Strauch K, Tai ES, Taylor K, Uitterlinden AG, van Duijn CM, Waldenberger M, Wee HL, Wei WB, Wilson G, Xuan D, Yao J, Zeng D, Zhao W, Zhu X, Zonderman AB, Becker DM, Deary IJ, Gieger C, Lakka TA, Lehtimäki T, North KE, Oldehinkel AJ, Penninx BWJH, Snieder H, Wang YX, Weir DR, Zheng W, Evans MK, Gauderman WJ, Gudnason V, Horta BL, Liu CT, Mook-Kanamori DO, Morrison AC, Pereira AC, Psaty BM, Amin N, Fox ER, Kooperberg C, Sim X, Bierut L, Rotter JI, Kardia SLR, Franceschini N, Rao DC, Fornage M. Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits. HGG Adv. 2021 Jan 14;2(1). doi: 10.1016/j.xhgg.2020.100013. Epub 2020 Oct 31. PMID: 34734193; PMCID: PMC8562625.
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HGG Adv. 2021 Jan 14;2(1). doi: 10.1016/j.xhgg.2020.100013. Epub 2020 Oct 31.

Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.

HGG advances

Daokun Sun, Melissa Richard, Solomon K Musani, Yun Ju Sung, Thomas W Winkler, Karen Schwander, Jin Fang Chai, Xiuqing Guo, Tuomas O Kilpeläinen, Dina Vojinovic, Hugues Aschard, Traci M Bartz, Lawrence F Bielak, Michael R Brown, Kumaraswamy Chitrala, Fernando P Hartwig, Andrea R V R Horimoto, Yongmei Liu, Alisa K Manning, Raymond Noordam, Albert V Smith, Sarah E Harris, Brigitte Kühnel, Leo-Pekka Lyytikäinen, Ilja M Nolte, Rainer Rauramaa, Peter J van der Most, Rujia Wang, Erin B Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Dan E Arking, Donna K Arnett, Ana Barac, Eric Boerwinkle, Ulrich Broeckel, Aravinda Chakravarti, Yii-Der Ida Chen, L Adrienne Cupples, Martha L Davigulus, Lisa de Las Fuentes, Renée de Mutsert, Paul S de Vries, Joseph A C Delaney, Ana V Diez Roux, Marcus Dörr, Jessica D Faul, Amanda M Fretts, Linda C Gallo, Hans Jörgen Grabe, C Charles Gu, Tamara B Harris, Catharina C A Hartman, Sami Heikkinen, M Arfan Ikram, Carmen Isasi, W Craig Johnson, Jost Bruno Jonas, Robert C Kaplan, Pirjo Komulainen, Jose E Krieger, Daniel Levy, Jianjun Liu, Kurt Lohman, Annemarie I Luik, Lisa W Martin, Thomas Meitinger, Yuri Milaneschi, Jeff R O'Connell, Walter R Palmas, Annette Peters, Patricia A Peyser, Laura Pulkki-Råback, Leslie J Raffel, Alex P Reiner, Kenneth Rice, Jennifer G Robinson, Frits R Rosendaal, Carsten Oliver Schmidt, Pamela J Schreiner, Lars Schwettmann, James M Shikany, Xiao-Ou Shu, Stephen Sidney, Mario Sims, Jennifer A Smith, Nona Sotoodehnia, Konstantin Strauch, E Shyong Tai, Kent Taylor, André G Uitterlinden, Cornelia M van Duijn, Melanie Waldenberger, Hwee-Lin Wee, Wen-Bin Wei, Gregory Wilson, Deng Xuan, Jie Yao, Donglin Zeng, Wei Zhao, Xiaofeng Zhu, Alan B Zonderman, Diane M Becker, Ian J Deary, Christian Gieger, Timo A Lakka, Terho Lehtimäki, Kari E North, Albertine J Oldehinkel, Brenda W J H Penninx, Harold Snieder, Ya-Xing Wang, David R Weir, Wei Zheng, Michele K Evans, W James Gauderman, Vilmundur Gudnason, Bernardo L Horta, Ching-Ti Liu, Dennis O Mook-Kanamori, Alanna C Morrison, Alexandre C Pereira, Bruce M Psaty, Najaf Amin, Ervin R Fox, Charles Kooperberg, Xueling Sim, Laura Bierut, Jerome I Rotter, Sharon L R Kardia, Nora Franceschini, Dabeeru C Rao, Myriam Fornage

Affiliations

  1. Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  2. These authors contributed equally to this work.
  3. Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  4. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
  5. Department of Genetic Epidemiology, University of Regensburg, Regensburg, 93040, Germany.
  6. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 119228, Singapore.
  7. 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.
  8. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK-2200, Denmark.
  9. Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  10. Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CA, The Netherlands.
  11. Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  12. Département de Génomes et Génétique, Institut Pasteur, Paris, 75015, France.
  13. Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, WA 98195, USA.
  14. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48108, USA.
  15. 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.
  16. Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 20892, USA.
  17. Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, RS 96010-610, Brazil.
  18. Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 1TH, UK.
  19. Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP 01246-903, Brazil.
  20. Division of Cardiology, Department of Medicine, Duke Molecular Physiology Institute Duke University School of Medicine, Durham, NC 27701, USA.
  21. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
  22. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  23. Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, 2311 EZ, The Netherlands.
  24. Department of Biostatistics, University of Michigan, Ann Arbor, MI 48108, USA.
  25. Icelandic Heart Association, Kopavogur, 201, Iceland.
  26. Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
  27. Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
  28. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Germany.
  29. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Germany.
  30. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33101, Finland.
  31. Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33101, Finland.
  32. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
  33. Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
  34. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA.
  35. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17489, Germany.
  36. DZHK (German Centre for Cardiovascular Health), Partner Site Greifswald, Greifswald, 17475, Germany.
  37. Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
  38. Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  39. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  40. Dean's Office, University of Kentucky College of Public Health, Lexington, KY 40563, USA.
  41. MedStar Heart and Vascular Institute, Washington, DC 20010, USA.
  42. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
  43. Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  44. Center for Human Genetics and Genomics, New York University School of Medicine, New York, NY 10016, USA.
  45. Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  46. NHLBI Framingham Heart Study, Framingham, MA 01702, USA.
  47. Division of Minority Health, Department of Epidemiology, University of Illinois, Chicago, IL, USA.
  48. Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO, USA.
  49. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2311 EZ, The Netherlands.
  50. College of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T5, Canada.
  51. Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA 19104, USA.
  52. Department of Internal Medicine B, University Medicine Greifswald, Greifswald, 17489, Germany.
  53. Cardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA 98195, USA.
  54. Department of Psychology, San Diego State University, San Diego, CA 92182, USA.
  55. Department Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, 17489, Germany.
  56. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
  57. Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
  58. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, 70100, Finland.
  59. Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, 70100, Finland.
  60. Department of Neurology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands.
  61. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY 10461, USA.
  62. Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
  63. Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, Mannheim, 68167, Germany.
  64. Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Capital Medical University, Beijing, China.
  65. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  66. Department of Medicine, Boston University, Boston, MA 02118, USA.
  67. Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, 138632, Singapore.
  68. Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA.
  69. Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Germany.
  70. Institute of Human Genetics, Technische Universität München, Munich, 81675, Germany.
  71. Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, 1081 HV, The Netherlands.
  72. Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  73. Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  74. Division of General Medicine, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
  75. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Neuherberg, D-85764, Germany.
  76. Faculty of Medicine, Department of Psychology and Logopedics, University of Helsinki, Helsinki, 0100, Finland.
  77. Division of Genetic and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA 92697, USA.
  78. Departments of Epidemiology and Medicine, University of Iowa, Iowa City, IA 52242, USA.
  79. Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17489, Germany.
  80. Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA.
  81. Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Germany.
  82. Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  83. Division of Research, Kaiser Permanente of Northern California, Oakland, CA 94612, USA.
  84. Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, WA 98195, USA.
  85. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Germany.
  86. Institute of Medical Informatics Biometry and Epidemiology, Ludwig-Maximilians-Universitat Munchen, Munich, 80539, Germany.
  87. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119077, Singapore.
  88. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands.
  89. Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
  90. German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, D-85764, Germany.
  91. Department of Pharmacy, Faculty of Science, National University of Singapore, 119077, Singapore.
  92. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
  93. Jackson Heart Study, School of Public Health, Jackson State University, Jackson, MS 39217, USA.
  94. Department of Biostatistics, University of North Carolina Gilling School of Global Public Health, Chapel Hill, NC 27599, USA.
  95. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
  96. Behavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21201, USA.
  97. German Center for Diabetes Research (DZD e.V.), Neuherberg, D-85764, Germany.
  98. Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Kuopio, 70211, Finland.
  99. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, 70211, Finland.
  100. Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, University of Tampere, Tampere, 33100, Finland.
  101. Department of Epidemiology, University of North Carolina Gilling School of Global Public Health, Chapel Hill, NC 27599, USA.
  102. Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
  103. Biostatistics, Preventive Medicine, University of Southern California, Los Angeles, CA 90007, USA.
  104. Faculty of Medicine, University of Iceland, Reykjavik, 102, Iceland.
  105. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2311 EZ, The Netherlands.
  106. Kaiser Permanente Washington Health Research Institute, Seattle, WA 98101, USA.
  107. Cardiology, Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  108. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.

PMID: 34734193 PMCID: PMC8562625 DOI: 10.1016/j.xhgg.2020.100013

Abstract

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (

Conflict of interest statement

Declaration of interest The authors declare no conflict of interests.

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