Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function
Year: 2021
Type: article
Study design: Observational Study
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.
Source: Scientific Reports
Authors: Tianzhong Yang, Victoria E. Jackson, Albert V. Smith, Han Chen, Traci M. Bartz, Colleen M. Sitlani, Bruce M. Psaty, Sina A. Gharib, George T. O’Connor, Josée Dupuis, Jiayi Xu, Kurt Lohman, Yongmei Liu, Stephen B. Kritchevsky, Patricia A. Cassano, Claudia Flexeder, Christian Gieger, Stefan Karrasch, Annette Peters, Holger Schulz, Sarah E. Harris, John M. Starr, Ian J. Deary, Ani Manichaikul, Elizabeth C. Oelsner, R. G. Barr, Kent D. Taylor, Stephen S. Rich, Tobias N. Bonten, Dennis O. Mook-Kanamori, Raymond Noordam, Ruifang Li-Gao, Marjo-Riitta Jarvelin, Matthias Wielscher, Natalie Terzikhan, Lies Lahousse, Guy Brusselle, Stefan Weiss, Ralf Ewert, Sven Gläser, Georg Homuth, Nick Shrine, Ian P. Hall, Martin Tobin, Stephanie J. London, Peng Wei, Alanna C. Morrison
Institutions: University of Minnesota, The University of Texas Health Science Center at Houston, University of Leicester, University of Michigan, University of Washington, Kaiser Permanente Washington Health Research Institute, Boston University, Framingham Heart Study, Cornell University, Icahn School of Medicine at Mount Sinai, Duke University, Duke Medical Center, Wake Forest University Health Sciences, Wake Forest University, Weill Cornell Medicine, Helmholtz Munich, German Center for Lung Research, Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin, Ludwig-Maximilians-Universität München, Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, University of Edinburgh, Alzheimer Scotland, University of Virginia, Columbia University, Columbia University Irving Medical Center, University of California, Los Angeles, Leiden University Medical Center, Imperial College London, University of Oulu, Ghent University Hospital, Erasmus MC, Universitätsmedizin Greifswald, Universität Greifswald, German Centre for Cardiovascular Research, Vivantes Klinikum, University of Nottingham, Glenfield Hospital, National Institute for Health and Care Research, National Institutes of Health, National Institute of Environmental Health Sciences, The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,990
Funders: U.S. Department of Health and Human Services, Wake Forest University, Johns Hopkins University, Wellcome Trust, National Institute for Health and Care Research, Royal Society, Royal Society of Edinburgh, Age UK, European Commission, University of Edinburgh, ZonMw, Erasmus Universiteit Rotterdam, Fonds Wetenschappelijk Onderzoek, Vlaamse regering, Centre for Cognitive Ageing and Cognitive Epidemiology, National Institutes of Health, Medical Research Council, Biotechnology and Biological Sciences Research Council, NIHR Leicester Biomedical Research Centre, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences, Common Fund, NHLBI Division of Intramural Research
Awards: G100949702, G1028935811, G1060904560, G109384441, G1108988672, G1114307781, G1156594538, Multi-Ethnic Study of Atherosclerosis (MESA) Study, G1174177975, G1177451333, G1184531726, G1200636938, G1203176964, G1216091320, G1261793039, Genetic Determinants of Visceral Adiposity, G1275337683, G1276754516, G1294553593, G129674942, G1304508731, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTER, G1305877031, G1373328648, Centre for Cognitive Ageing & Cognitive Epidemiology, G1409423729, DYNAMICS OF HEALTH,AGING, AND BODY COMPOSITION, G1446319095, G1481755545, G1483344193, G1488503895, G1490530680, G1497137905, G1508998135, G1516086731, G152041249, G1522144118, G1522370804, G1558725192, G156023790, G1591262631, G1640378483, G1653431188, G1686417863, UCLA Clinical and Translational Science Institute, G1735617348, G1735726520, G1740741465, G1747129958, G1752571699, G17630474, G1788514665, G1823732541, G1851406594, G185733499, G1900562043, G1922428914, G1982334678, G1983464145, G2009815313, G2050812788, G2070131968, SUBCLINICAL CARDIOVASCULAR DISEASE COORDINATING CENTER, G2095596736, G2095942735, G2130630498, G2130928551, G2144938473, G2146332128, G2169623015, G2178492673, G2215959655, G22458031, G2255094795, G2262505034, G2262782284, G2281899837, G2326437104, G2334180555, G2352317866, G2417647834, G2440993854, G250621538, G2545476352, G2553282249, G2568281471, MESA Family Study, G2574430291, G2585438117, G2588136129, G2607172802, G2622081593, G2663518188, G2726417417, G2733059257, G2750604849, G2760875884, G2779429302, G278200998, G2782535235, G2815873878, G2837638605, G283874107, G286372155, G2905571579, G290884426, G291913881, G2952093371, Large-scale genomic epidemiology approaches to study the natural history of lung function and COPD, G296458788, G297113894, G2989067737, G303055330, G3064274663, G3089759439, G3093995152, G3106377335, HEALTH ABC--COORDINATING UNIT, G3161396180, G3205625555, G3252259982, MESA Family Study, G33312777, G3342643523, G339263803, G3405256882, G3410090833, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G3436664722, G343705321, G3458159861, G350785449, G3561683115, G3561803360, G3568487487, G3581052147, G3595232572, G3647016462, G3667269547, G3687594596, G3692229207, G36937976, G370977179, G3712480900, G3744596180, G3776664567, G379100749, G3809606526, G3819938352, G3828973723, G3856778523, G3860090032, G3933842093, G3973572274, G3990748671, G399481048, G4036023366, NIHR Senior Investigator Award, G4065540706, G4079570820, G4118980254, G4157760435, G4186273061, G4208240127, G4222455271, G4246339746, G4296038422, G4309390892, G4312169524, G4341976608, G4401650913, G4429312988, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G4459840562, G4512137732, G4549827071, G4590187187, G4597579782, G4653673457, G4678087642, G4688346656, G4739409156, G4747441672, G4771937603, G4790942633, G4845182219, G485517832, G4976486911, G4986157935, Hypercoagulability and Chronic Lung Disease in Older Adults, G5023962947, MESA Family Study, G5067462658, G5075046117, G5077810636, G5084286802, G5088122703, G5092239925, G5108002584, G5164707915, G5191018426, G5234713383, G5254636657, G5281659474, NIHR Senior Investigator Award, G5352314984, G537455924, SLEEP AND ENTERTAIMENT OF SCN FUNCTION, G5426525723, G5473995689, G5518071353, G5558208168, G556483404, G55907201, G5605591545, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G562502316, G5653954166, G5654179670, G567477586, G5686942884, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G5755700318, G5770678025, G5787256936, G581554933, G5832823749, G5850737185, G5909482378, G5916532371, G5928944960, G5940222141, G5957994314, G5999060983, PATHOLOGY MONITORING OF NIH AGED HYBRID RODENT COLONIES, G6060132884, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY, G6093314662, G6095866717, G611626141, G611940047, G6130894301, G6148500974, G6177097893, G6177195516, G6265582126, G6359107525, G6370105032, G6372296772, G6393075246, G6398255701, Institute for Clinical and Translational Research, G6436857277, G6476413162, G6480224857, G6514094751, G6541715359, G6580025376, G6594067713, G660031408, G66341962, G666546157, G670738241, SNP HEALTH ASSOCIATION RESOURCE (SHARE), G6739173425, G6742279884, G6767999137, G6837735701, G6856766826, G687975376, THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY, G7007046788, Diabetes Endocrinology Research Center, G7047602405, G7055397874, G706815212, G7093047072, G7114400168, G7132376052, G713258703, G7155745631, G7166352866, G718988473, G7249398899, MESA Family Study, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G7270333588, G7278374444, G7333737664, G738360740, G7399262704, G740377980, G7419815775, G7495086035, G7522350138, G7535686976, G772876839, G7770036369, G7771854671, G7808459314, G78770644, G7902383717, Genomic and Transcriptomic Analysis of Emphysema and Subclinical ILD, G7924587209, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, G7998842548, G805458286, Clinical and Translational Science Award, G8083541232, G8145863542, G8163173899, G818308888, G820615960, G8215766172, G8267674335, G8492131798, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTER, G8631103115, G8683204365, G868570109, G8698877469, G8733687393, G8738262636, G8777596830, G8823037953, G8852914737, Combined Cardiopulmonary Failure in COPD: SPIROMICS HF, G88852782, Building on GWAS for NHLBI-disease: the CHARGE consortium, G9000004549, G9000004784, G9000006353, G9000011680, G9000017360, G9000019818, G9000023087, G9000025517, G9000026317, G9000031392, G9000038858, G9000050004, G9000062084, G9000063950, G9000065698, G9000124674, G9000125886, G9000140433, G9000143535, G9000166311, G9000230236, G9000234302, G9000246407, G9000326552, G9000330609, Determining genomic and host-environment contributions to IBD phenotypes, G936600500, G945304896, G94668252, G960921318, Albuminuria and incident chronic lung disease exacerbations in five population-based cohorts, G991334795
OpenAlex ID: W3203509668