Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function

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Fältnamn	Indikatorer	Metadata
000		06215naa a2201357 4500
001		oai:DiVA.org:uu-191199
003		SwePub
008		130109s2012 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1911992 URI
024	7	a https://doi.org/10.1371/journal.pgen.10030982 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Hancock, Dana B4 aut
245	1 0	a Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function
264		c 2012-12-20
264	1	b Public Library of Science (PLoS),c 2012
338		a electronic2 rdacarrier
520		a Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/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 FEV1 and FEV1/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 PJMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest PJMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 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.
700	1	a Artigas, María Soler4 aut
700	1	a Gharib, Sina A4 aut
700	1	a Henry, Amanda4 aut
700	1	a Manichaikul, Ani4 aut
700	1	a Ramasamy, Adaikalavan4 aut
700	1	a Loth, Daan W4 aut
700	1	a Imboden, Medea4 aut
700	1	a Koch, Beate4 aut
700	1	a McArdle, Wendy L4 aut
700	1	a Smith, Albert V4 aut
700	1	a Smolonska, Joanna4 aut
700	1	a Sood, Akshay4 aut
700	1	a Tang, Wenbo4 aut
700	1	a Wilk, Jemma B4 aut
700	1	a Zhai, Guangju4 aut
700	1	a Zhao, Jing Hua4 aut
700	1	a Aschard, Hugues4 aut
700	1	a Burkart, Kristin M4 aut
700	1	a Curjuric, Ivan4 aut
700	1	a Eijgelsheim, Mark4 aut
700	1	a Elliott, Paul4 aut
700	1	a Gu, Xiangjun4 aut
700	1	a Harris, Tamara B4 aut
700	1	a Janson, Christeru Uppsala universitet,Lungmedicin och allergologi,Lung och allergifoskning4 aut0 (Swepub:uu)chrisjn
700	1	a Homuth, Georg4 aut
700	1	a Hysi, Pirro G4 aut
700	1	a Liu, Jason Z4 aut
700	1	a Loehr, Laura R4 aut
700	1	a Lohman, Kurt4 aut
700	1	a Loos, Ruth J F4 aut
700	1	a Manning, Alisa K4 aut
700	1	a Marciante, Kristin D4 aut
700	1	a Obeidat, Ma'en4 aut
700	1	a Postma, Dirkje S4 aut
700	1	a Aldrich, Melinda C4 aut
700	1	a Brusselle, Guy G4 aut
700	1	a Chen, Ting-Hsu4 aut
700	1	a Eiriksdottir, Gudny4 aut
700	1	a Franceschini, Nora4 aut
700	1	a Heinrich, Joachim4 aut
700	1	a Rotter, Jerome I4 aut
700	1	a Wijmenga, Cisca4 aut
700	1	a Williams, O Dale4 aut
700	1	a Bentley, Amy R4 aut
700	1	a Hofman, Albert4 aut
700	1	a Laurie, Cathy C4 aut
700	1	a Lumley, Thomas4 aut
700	1	a Morrison, Alanna C4 aut
700	1	a Joubert, Bonnie R4 aut
700	1	a Rivadeneira, Fernando4 aut
700	1	a Couper, David J4 aut
700	1	a Kritchevsky, Stephen B4 aut
700	1	a Liu, Yongmei4 aut
700	1	a Wjst, Matthias4 aut
700	1	a Wain, Louise V4 aut
700	1	a Vonk, Judith M4 aut
700	1	a Uitterlinden, André G4 aut
700	1	a Rochat, Thierry4 aut
700	1	a Rich, Stephen S4 aut
700	1	a Psaty, Bruce M4 aut
700	1	a O'Connor, George T4 aut
700	1	a North, Kari E4 aut
700	1	a Mirel, Daniel B4 aut
700	1	a Meibohm, Bernd4 aut
700	1	a Launer, Lenore J4 aut
700	1	a Khaw, Kay-Tee4 aut
700	1	a Hartikainen, Anna-Liisa4 aut
700	1	a Hammond, Christopher J4 aut
700	1	a Gläser, Sven4 aut
700	1	a Marchini, Jonathan4 aut
700	1	a Kraft, Peter4 aut
700	1	a Wareham, Nicholas J4 aut
700	1	a Völzke, Henry4 aut
700	1	a Stricker, Bruno H C4 aut
700	1	a Spector, Timothy D4 aut
700	1	a Probst-Hensch, Nicole M4 aut
700	1	a Jarvis, Deborah4 aut
700	1	a Jarvelin, Marjo-Riitta4 aut
700	1	a Heckbert, Susan R4 aut
700	1	a Gudnason, Vilmundur4 aut
700	1	a Boezen, H Marike4 aut
700	1	a Barr, R Graham4 aut
700	1	a Cassano, Patricia A4 aut
700	1	a Strachan, David P4 aut
700	1	a Fornage, Myriam4 aut
700	1	a Hall, Ian P4 aut
700	1	a Dupuis, Josée4 aut
700	1	a Tobin, Martin D4 aut
700	1	a London, Stephanie J4 aut
710	2	a Uppsala universitetb Lungmedicin och allergologi4 org
773	0	t PLoS geneticsd : Public Library of Science (PLoS)g 8:12, s. e1003098-q 8:12<e1003098-x 1553-7404
856	4	u https://uu.diva-portal.org/smash/get/diva2:585031/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4	u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003098&type=printable
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-191199
856	4 8	u https://doi.org/10.1371/journal.pgen.1003098

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By the author/editor: Hancock, Dana B; Artigas, María S ...; Gharib, Sina A; Henry, Amanda; Manichaikul, Ani; Ramasamy, Adaika ...; show more...; Loth, Daan W; Imboden, Medea; Koch, Beate; McArdle, Wendy L; Smith, Albert V; Smolonska, Joann ...; Sood, Akshay; Tang, Wenbo; Wilk, Jemma B; Zhai, Guangju; Zhao, Jing Hua; Aschard, Hugues; Burkart, Kristin ...; Curjuric, Ivan; Eijgelsheim, Mar ...; Elliott, Paul; Gu, Xiangjun; Harris, Tamara B; Janson, Christer; Homuth, Georg; Hysi, Pirro G; Liu, Jason Z; Loehr, Laura R; Lohman, Kurt; Loos, Ruth J F; Manning, Alisa K; Marciante, Krist ...; Obeidat, Ma'en; Postma, Dirkje S; Aldrich, Melinda ...; Brusselle, Guy G; Chen, Ting-Hsu; Eiriksdottir, Gu ...; Franceschini, No ...; Heinrich, Joachi ...; Rotter, Jerome I; Wijmenga, Cisca; Williams, O Dale; Bentley, Amy R; Hofman, Albert; Laurie, Cathy C; Lumley, Thomas; Morrison, Alanna ...; Joubert, Bonnie ...; Rivadeneira, Fer ...; Couper, David J; Kritchevsky, Ste ...; Liu, Yongmei; Wjst, Matthias; Wain, Louise V; Vonk, Judith M; Uitterlinden, An ...; Rochat, Thierry; Rich, Stephen S; Psaty, Bruce M; O'Connor, George ...; North, Kari E; Mirel, Daniel B; Meibohm, Bernd; Launer, Lenore J; Khaw, Kay-Tee; Hartikainen, Ann ...; Hammond, Christo ...; Gläser, Sven; Marchini, Jonath ...; Kraft, Peter; Wareham, Nichola ...; Völzke, Henry; Stricker, Bruno ...; Spector, Timothy ...; Probst-Hensch, N ...; Jarvis, Deborah; Jarvelin, Marjo- ...; Heckbert, Susan ...; Gudnason, Vilmun ...; Boezen, H Marike; Barr, R Graham; Cassano, Patrici ...; Strachan, David ...; Fornage, Myriam; Hall, Ian P; Dupuis, Josée; Tobin, Martin D; London, Stephani ...; show less...

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