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Abstract
Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV1), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were significantly associated with FEV1. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function.
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Details
Title
Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function
Author
Yang Tianzhong 1 ; Jackson, Victoria E 2 ; Smith, Albert V 3 ; Chen, Han 4 ; Bartz, Traci M 5 ; Sitlani, Colleen M 6 ; Psaty, Bruce M 7 ; Gharib, Sina A 8 ; O’Connor George T 9 ; Dupuis Josée 10 ; Xu, Jiayi 11 ; Lohman, Kurt 12 ; Liu, Yongmei 12 ; Kritchevsky, Stephen B 13 ; Cassano, Patricia A 14 ; Flexeder Claudia 15 ; Gieger, Christian 16 ; Karrasch Stefan 17 ; Peters, Annette 18 ; Schulz, Holger 19 ; Harris, Sarah E 20 ; Starr, John M 21 ; Deary, Ian J 20 ; Manichaikul Ani 22 ; Oelsner, Elizabeth C 23 ; Barr, R G 24 ; Taylor, Kent D 25 ; Rich, Stephen S 26 ; Bonten, Tobias N 27 ; Mook-Kanamori, Dennis O 28 ; Noordam, Raymond 29 ; Li-Gao, Ruifang 30 ; Jarvelin Marjo-Riitta 31 ; Wielscher Matthias 32 ; Terzikhan Natalie 33 ; Lahousse Lies 33 ; Brusselle Guy 33 ; Weiss, Stefan 34 ; Ewert Ralf 35 ; Gläser Sven 36 ; Homuth Georg 37 ; Shrine Nick 2 ; Hall, Ian P 38 ; Tobin, Martin 39 ; London, Stephanie J 40 ; Peng, Wei 41 ; Morrison, Alanna C 42
1 The University of Texas Health Science Center at Houston, Department of Biostatistics and Data Science, School of Public Health, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401); University of Minnesota, Division of Biostatistics, School of Public Health, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657)
2 University of Leicester, Department of Health Sciences, Leicester, UK (GRID:grid.9918.9) (ISNI:0000 0004 1936 8411)
3 University of Michigan, Department of Biostatistics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)
4 The University of Texas Health Science Center at Houston, Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401); The University of Texas Health Science Center at Houston, Center for Precision Health, School of Public Health and School of Biomedical Informatics, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401)
5 University of Washington, Department of Biostatistics, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); University of Washington, Cardiovascular Health Research Unit, Department of Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
6 University of Washington, Cardiovascular Health Research Unit, Department of Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
7 University of Washington, Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); Kaiser Permanente Washington Health Research Institute, Seattle, USA (GRID:grid.488833.c) (ISNI:0000 0004 0615 7519)
8 University of Washington, Division of Pulmonary, Critical Care, and Sleep, Department of Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
9 Boston University School of Medicine, Department of Medicine, Pulmonary Center, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, USA (GRID:grid.510954.c) (ISNI:0000 0004 0444 3861)
10 Boston University School of Public Health, Department of Biostatistics, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
11 Icahn School of Medicine at Mount Sinai, Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomic Sciences, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Cornell University, Division of Nutritional Sciences, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X)
12 Duke University School of Medicine, Division of Cardiology, Department of Medicine, Duke Molecular Physiology Institute, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961)
13 Wake Forest School of Medicine, Sticht Center for Healthy Aging and Alzheimer’s Prevention, Winston-Salem, USA (GRID:grid.241167.7) (ISNI:0000 0001 2185 3318)
14 Cornell University, Division of Nutritional Sciences, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X); Weill Cornell Medical College, Department of Healthcare Policy and Research, New York, USA (GRID:grid.5386.8) (ISNI:000000041936877X)
15 German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525)
16 German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525)
17 German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Ludwig-Maximilians-Universität, Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X); Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany (GRID:grid.452624.3)
18 German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Ludwig-Maximilians-Universität München, Institute for Medical Information Processing, Biometry and Epidemiology, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X)
19 German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany (GRID:grid.452624.3)
20 The University of Edinburgh, Department of Psychology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); The University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988)
21 The University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); The University of Edinburgh, Alzheimer Scotland Dementia Research Centre, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988)
22 University of Virginia, Department of Public Health Sciences, Center for Public Health Genomics, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X); University of Virginia, Division of Biostatistics and Epidemiology, Department of Public Health Sciences, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X)
23 Columbia University, Department of Medicine, College of Physicians and Surgeons, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729); Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729)
24 Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729); Columbia University Medical Center, Department of Medicine, Department of Epidemiology, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675)
25 University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
26 University of Virginia, Department of Public Health Sciences, Center for Public Health Genomics, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X)
27 Leiden University Medical Center, Department of Public Health and Primary Care, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978)
28 Leiden University Medical Center, Department of Clinical Epidemiology, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978); Leiden University Medical Center, Department of Public Health and Primary Care, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978)
29 Leiden University Medical Center, Division of Gerontology and Geriatrics, Department of Internal Medicine, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978)
30 Leiden University Medical Center, Department of Clinical Epidemiology, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978)
31 Imperial College London, Department of Epidemiology and Biostatistics, School of Public Health, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); University of Oulu, Faculty of Medicine, Center for Life Course Health Research, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873); University of Oulu, Biocenter of Oulu, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873)
32 Imperial College London, Department of Epidemiology and Biostatistics, School of Public Health, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
33 Erasmus University Medical Center, Department of Epidemiology, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Ghent University Hospital, Department of Respiratory Medicine, Ghent, Belgium (GRID:grid.410566.0) (ISNI:0000 0004 0626 3303)
34 University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany (GRID:grid.5603.0); DZHK (German Centre for Cardiovascular Research), Greifswald, Germany (GRID:grid.452396.f) (ISNI:0000 0004 5937 5237)
35 University Medicine Greifswald, Division of Cardiology, Pneumology, Infectious Diseases, Intensive Care Medicine, Department of Internal Medicine B, Greifswald, Germany (GRID:grid.5603.0)
36 University Medicine Greifswald, Division of Cardiology, Pneumology, Infectious Diseases, Intensive Care Medicine, Department of Internal Medicine B, Greifswald, Germany (GRID:grid.5603.0); Vivantes Hospital Berlin Spandau, Department of Internal Medicine, Berlin, Germany (GRID:grid.5603.0)
37 University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany (GRID:grid.5603.0)
38 University of Nottingham, Division of Respiratory Medicine, Nottingham, UK (GRID:grid.4563.4) (ISNI:0000 0004 1936 8868)
39 University of Leicester, Department of Health Sciences, Leicester, UK (GRID:grid.9918.9) (ISNI:0000 0004 1936 8411); Leicester Respiratory Biomedical Research Unit, National Institute for Health Research, Glenfield Hospital, Leicester, UK (GRID:grid.412925.9) (ISNI:0000 0004 0400 6581)
40 National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Epidemiology Branch, Research Triangle Park, USA (GRID:grid.280664.e) (ISNI:0000 0001 2110 5790)
41 The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776)
42 The University of Texas Health Science Center at Houston, Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401)
1 The University of Texas Health Science Center at Houston, Department of Biostatistics and Data Science, School of Public Health, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401); University of Minnesota, Division of Biostatistics, School of Public Health, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657)
2 University of Leicester, Department of Health Sciences, Leicester, UK (GRID:grid.9918.9) (ISNI:0000 0004 1936 8411)
3 University of Michigan, Department of Biostatistics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)
4 The University of Texas Health Science Center at Houston, Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401); The University of Texas Health Science Center at Houston, Center for Precision Health, School of Public Health and School of Biomedical Informatics, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401)
5 University of Washington, Department of Biostatistics, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); University of Washington, Cardiovascular Health Research Unit, Department of Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
6 University of Washington, Cardiovascular Health Research Unit, Department of Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
7 University of Washington, Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657); Kaiser Permanente Washington Health Research Institute, Seattle, USA (GRID:grid.488833.c) (ISNI:0000 0004 0615 7519)
8 University of Washington, Division of Pulmonary, Critical Care, and Sleep, Department of Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
9 Boston University School of Medicine, Department of Medicine, Pulmonary Center, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, USA (GRID:grid.510954.c) (ISNI:0000 0004 0444 3861)
10 Boston University School of Public Health, Department of Biostatistics, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
11 Icahn School of Medicine at Mount Sinai, Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomic Sciences, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Cornell University, Division of Nutritional Sciences, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X)
12 Duke University School of Medicine, Division of Cardiology, Department of Medicine, Duke Molecular Physiology Institute, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961)
13 Wake Forest School of Medicine, Sticht Center for Healthy Aging and Alzheimer’s Prevention, Winston-Salem, USA (GRID:grid.241167.7) (ISNI:0000 0001 2185 3318)
14 Cornell University, Division of Nutritional Sciences, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X); Weill Cornell Medical College, Department of Healthcare Policy and Research, New York, USA (GRID:grid.5386.8) (ISNI:000000041936877X)
15 German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525)
16 German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525)
17 German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Ludwig-Maximilians-Universität, Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X); Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany (GRID:grid.452624.3)
18 German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Ludwig-Maximilians-Universität München, Institute for Medical Information Processing, Biometry and Epidemiology, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X)
19 German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany (GRID:grid.452624.3)
20 The University of Edinburgh, Department of Psychology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); The University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988)
21 The University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); The University of Edinburgh, Alzheimer Scotland Dementia Research Centre, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988)
22 University of Virginia, Department of Public Health Sciences, Center for Public Health Genomics, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X); University of Virginia, Division of Biostatistics and Epidemiology, Department of Public Health Sciences, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X)
23 Columbia University, Department of Medicine, College of Physicians and Surgeons, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729); Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729)
24 Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729); Columbia University Medical Center, Department of Medicine, Department of Epidemiology, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675)
25 University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
26 University of Virginia, Department of Public Health Sciences, Center for Public Health Genomics, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X)
27 Leiden University Medical Center, Department of Public Health and Primary Care, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978)
28 Leiden University Medical Center, Department of Clinical Epidemiology, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978); Leiden University Medical Center, Department of Public Health and Primary Care, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978)
29 Leiden University Medical Center, Division of Gerontology and Geriatrics, Department of Internal Medicine, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978)
30 Leiden University Medical Center, Department of Clinical Epidemiology, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978)
31 Imperial College London, Department of Epidemiology and Biostatistics, School of Public Health, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); University of Oulu, Faculty of Medicine, Center for Life Course Health Research, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873); University of Oulu, Biocenter of Oulu, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873)
32 Imperial College London, Department of Epidemiology and Biostatistics, School of Public Health, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
33 Erasmus University Medical Center, Department of Epidemiology, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Ghent University Hospital, Department of Respiratory Medicine, Ghent, Belgium (GRID:grid.410566.0) (ISNI:0000 0004 0626 3303)
34 University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany (GRID:grid.5603.0); DZHK (German Centre for Cardiovascular Research), Greifswald, Germany (GRID:grid.452396.f) (ISNI:0000 0004 5937 5237)
35 University Medicine Greifswald, Division of Cardiology, Pneumology, Infectious Diseases, Intensive Care Medicine, Department of Internal Medicine B, Greifswald, Germany (GRID:grid.5603.0)
36 University Medicine Greifswald, Division of Cardiology, Pneumology, Infectious Diseases, Intensive Care Medicine, Department of Internal Medicine B, Greifswald, Germany (GRID:grid.5603.0); Vivantes Hospital Berlin Spandau, Department of Internal Medicine, Berlin, Germany (GRID:grid.5603.0)
37 University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany (GRID:grid.5603.0)
38 University of Nottingham, Division of Respiratory Medicine, Nottingham, UK (GRID:grid.4563.4) (ISNI:0000 0004 1936 8868)
39 University of Leicester, Department of Health Sciences, Leicester, UK (GRID:grid.9918.9) (ISNI:0000 0004 1936 8411); Leicester Respiratory Biomedical Research Unit, National Institute for Health Research, Glenfield Hospital, Leicester, UK (GRID:grid.412925.9) (ISNI:0000 0004 0400 6581)
40 National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Epidemiology Branch, Research Triangle Park, USA (GRID:grid.280664.e) (ISNI:0000 0001 2110 5790)
41 The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776)
42 The University of Texas Health Science Center at Houston, Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401)
Publication year
2021
Publication date
2021
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2577605077
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.