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Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.
Tuesday,2013-10-01 10:15 America/Los_Angeles — poolea2
| Title | Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Hancock, DB, Artigas, MSoler, Gharib, SA, Henry, A, Manichaikul, A, Ramasamy, A, Loth, DW, Imboden, M, Koch, B, McArdle, WL, Smith, AV, Smolonska, J, Sood, A, Tang, W, Wilk, JB, Zhai, G, Zhao, JH, Aschard, H, Burkart, KM, Curjuric, I, Eijgelsheim, M, Elliott, P, Gu, X, Harris, TB, Janson, C, Homuth, G, Hysi, PG, Liu, JZ, Loehr, LR, Lohman, K, Loos, RJF, Manning, AK, Marciante, KD, Obeidat, M'en, Postma, DS, Aldrich, MC, Brusselle, GG, Chen, T-H, Eiriksdottir, G, Franceschini, N, Heinrich, J, Rotter, JI, Wijmenga, C, O Williams, D, Bentley, AR, Hofman, A, Laurie, CC, Lumley, T, Morrison, AC, Joubert, BR, Rivadeneira, F, Couper, DJ, Kritchevsky, SB, Liu, Y, Wjst, M, Wain, LV, Vonk, JM, Uitterlinden, AG, Rochat, T, Rich, SS, Psaty, BM, O'Connor, GT, North, KE, Mirel, DB, Meibohm, B, Launer, LJ, Khaw, K-T, Hartikainen, A-L, Hammond, CJ, Gläser, S, Marchini, J, Kraft, P, Wareham, NJ, Völzke, H, Stricker, BHC, Spector, TD, Probst-Hensch, NM, Jarvis, D, Jarvelin, M-R, Heckbert, SR, Gudnason, V, H Boezen, M, R Barr, G, Cassano, PA, Strachan, DP, Fornage, M, Hall, IP, Dupuis, J, Tobin, MD, London, SJ |
| Journal | PLoS Genet |
| Volume | 8 |
| Issue | 12 |
| Pagination | e1003098 |
| Date Published | 2012 |
| ISSN | 1553-7404 |
| Keywords | Forced Expiratory Volume, Gene Expression, Genome, Human, Genome-Wide Association Study, HLA-DQ Antigens, HLA-DQ beta-Chains, Humans, Lung, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Potassium Channels, Inwardly Rectifying, Pulmonary Disease, Chronic Obstructive, Receptors, Cell Surface, Smoking, SOX9 Transcription Factor, Vital Capacity |
| Abstract | <p>Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.</p> |
| DOI | 10.1371/journal.pgen.1003098 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 23284291 |
| PubMed Central ID | PMC3527213 |
| Grant List | UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01-HC-45205 / HC / NHLBI NIH HHS / United States N01-HC-95162 / HC / NHLBI NIH HHS / United States U01-HG-004446 / HG / NHGRI NIH HHS / United States N01-HC-05187 / HC / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States 1R01EY018246 / EY / NEI NIH HHS / United States N01-HC-48047 / HC / NHLBI NIH HHS / United States RC1AG035835 / AG / NIA NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States HHSN268201100005C / / PHS HHS / United States HL105756 / HL / NHLBI NIH HHS / United States RR-024156 / RR / NCRR NIH HHS / United States N01AG62101 / AG / NIA NIH HHS / United States N01-HC-95163 / HC / NHLBI NIH HHS / United States G1000861 / / Medical Research Council / United Kingdom 079895 / / Wellcome Trust / United Kingdom N01-HC-95168 / HC / NHLBI NIH HHS / United States AG-15928 / AG / NIA NIH HHS / United States R21DK084529 / DK / NIDDK NIH HHS / United States R01 HL077612 / HL / NHLBI NIH HHS / United States HHSN268201100009C / / PHS HHS / United States 5R01MH63706:02 / MH / NIMH NIH HHS / United States N01-HC-45204 / HC / NHLBI NIH HHS / United States N01-HC-95159 / HC / NHLBI NIH HHS / United States G1000143 / / Medical Research Council / United Kingdom 1R01AG032098-01A1 / AG / NIA NIH HHS / United States 1RL1MH083268-01 / MH / NIMH NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States N01-HC-95095 / HC / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States N01-HC-95165 / HC / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States R01-HL-084099 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States HHSN268201100010C / / PHS HHS / United States N01-HC-48050 / HC / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States MC_U106179471 / / Medical Research Council / United Kingdom N01-HC-85082 / HC / NHLBI NIH HHS / United States R01-HL077612 / HL / NHLBI NIH HHS / United States HL075366 / HL / NHLBI NIH HHS / United States / / Intramural NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01-HC-45134 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States HHSN268201100008C / / PHS HHS / United States 14136 / / Cancer Research UK / United Kingdom HHSN268201100012C / / PHS HHS / United States N01AG2103 / AG / NIA NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States U01-HG-004424 / HG / NHGRI NIH HHS / United States N01-HC-95169 / HC / NHLBI NIH HHS / United States G0401527 / / Medical Research Council / United Kingdom N01-HC-95164 / HC / NHLBI NIH HHS / United States N01-HC-48049 / HC / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States 090532 / / Wellcome Trust / United Kingdom N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01-HC-95160 / HC / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States HHSN268201100007C / / PHS HHS / United States R01 HL075476 / HL / NHLBI NIH HHS / United States G0902313 / / Medical Research Council / United Kingdom U01-HG-004729 / HG / NHGRI NIH HHS / United States N01-AG-12100 / AG / NIA NIH HHS / United States HHSN268201100011C / / PHS HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-95161 / HC / NHLBI NIH HHS / United States U01DK062418 / DK / NIDDK NIH HHS / United States HHSN268201200036C / / PHS HHS / United States 068545/Z/02 / / Wellcome Trust / United Kingdom HHSN268200782096C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States 5R01HL087679-02 / HL / NHLBI NIH HHS / United States N01AG62106 / AG / NIA NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States N01-HC-48048 / HC / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States HHSN268201100006C / / PHS HHS / United States N01-HC-95166 / HC / NHLBI NIH HHS / United States SRF/01/010 / / Department of Health / United Kingdom MC_U106188470 / / Medical Research Council / United Kingdom 076113/B/04/Z / / Wellcome Trust / United Kingdom G0000934 / / Medical Research Council / United Kingdom RC1-HL100543 / HL / NHLBI NIH HHS / United States UL 1RR033176 / RR / NCRR NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States Z01ES043012 / ES / NIEHS NIH HHS / United States N01 HC095159 / HC / NHLBI NIH HHS / United States N01-HC-95167 / HC / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States |