Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.

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Wain, Louise V (author)

Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.

Article/chapterEnglish2017

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2017-02-06
Springer Science and Business Media LLC,2017
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LIBRIS-ID:oai:DiVA.org:uu-317994
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-317994URI
https://doi.org/10.1038/ng.3787DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.

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Shrine, Nick (author)
Artigas, María Soler (author)
Erzurumluoglu, A Mesut (author)
Noyvert, Boris (author)
Bossini-Castillo, Lara (author)
Obeidat, Ma'en (author)
Henry, Amanda P (author)
Portelli, Michael A (author)
Hall, Robert J (author)
Billington, Charlotte K (author)
Rimington, Tracy L (author)
Fenech, Anthony G (author)
John, Catherine (author)
Blake, Tineka (author)
Jackson, Victoria E (author)
Allen, Richard J (author)
Prins, Bram P (author)
Campbell, Archie (author)
Porteous, David J (author)
Jarvelin, Marjo-Riitta (author)
Wielscher, Matthias (author)
James, Alan L (author)
Hui, Jennie (author)
Wareham, Nicholas J (author)
Zhao, Jing Hua (author)
Wilson, James F (author)
Joshi, Peter K (author)
Stubbe, Beate (author)
Rawal, Rajesh (author)
Schulz, Holger (author)
Imboden, Medea (author)
Probst-Hensch, Nicole M (author)
Karrasch, Stefan (author)
Gieger, Christian (author)
Deary, Ian J (author)
Harris, Sarah E (author)
Marten, Jonathan (author)
Rudan, Igor (author)
Enroth, StefanUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)stenr451 (author)
Gyllensten, Ulf B.Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)ulfgyll (author)
Kerr, Shona M (author)
Polasek, Ozren (author)
Kähönen, Mika (author)
Surakka, Ida (author)
Vitart, Veronique (author)
Hayward, Caroline (author)
Lehtimäki, Terho (author)
Raitakari, Olli T (author)
Evans, David M (author)
Henderson, A John (author)
Pennell, Craig E (author)
Wang, Carol A (author)
Sly, Peter D (author)
Wan, Emily S (author)
Busch, Robert (author)
Hobbs, Brian D (author)
Litonjua, Augusto A (author)
Sparrow, David W (author)
Gulsvik, Amund (author)
Bakke, Per S (author)
Crapo, James D (author)
Beaty, Terri H (author)
Hansel, Nadia N (author)
Mathias, Rasika A (author)
Ruczinski, Ingo (author)
Barnes, Kathleen C (author)
Bossé, Yohan (author)
Joubert, Philippe (author)
van den Berge, Maarten (author)
Brandsma, Corry-Anke (author)
Paré, Peter D (author)
Sin, Don D (author)
Nickle, David C (author)
Hao, Ke (author)
Gottesman, Omri (author)
Dewey, Frederick E (author)
Bruse, Shannon E (author)
Carey, David J (author)
Kirchner, H Lester (author)
Jonsson, Stefan (author)
Thorleifsson, Gudmar (author)
Jonsdottir, Ingileif (author)
Gislason, Thorarinn (author)
Stefansson, Kari (author)
Schurmann, Claudia (author)
Nadkarni, Girish (author)
Bottinger, Erwin P (author)
Loos, Ruth J F (author)
Walters, Robin G (author)
Chen, Zhengming (author)
Millwood, Iona Y (author)
Vaucher, Julien (author)
Kurmi, Om P (author)
Li, Liming (author)
Hansell, Anna L (author)
Brightling, Chris (author)
Zeggini, Eleftheria (author)
Cho, Michael H (author)
Silverman, Edwin K (author)
Sayers, Ian (author)
Trynka, Gosia (author)
Morris, Andrew P (author)
Strachan, David P (author)
Hall, Ian P (author)
Tobin, Martin D (author)
Uppsala universitetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

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In:Nature Genetics: Springer Science and Business Media LLC49:3, s. 416-4251061-40361546-1718

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By the author/editor: Wain, Louise V; Shrine, Nick; Artigas, María S ...; Erzurumluoglu, A ...; Noyvert, Boris; Bossini-Castillo ...; show more...; Obeidat, Ma'en; Henry, Amanda P; Portelli, Michae ...; Hall, Robert J; Billington, Char ...; Rimington, Tracy ...; Fenech, Anthony ...; John, Catherine; Blake, Tineka; Jackson, Victori ...; Allen, Richard J; Prins, Bram P; Campbell, Archie; Porteous, David ...; Jarvelin, Marjo- ...; Wielscher, Matth ...; James, Alan L; Hui, Jennie; Wareham, Nichola ...; Zhao, Jing Hua; Wilson, James F; Joshi, Peter K; Stubbe, Beate; Rawal, Rajesh; Schulz, Holger; Imboden, Medea; Probst-Hensch, N ...; Karrasch, Stefan; Gieger, Christia ...; Deary, Ian J; Harris, Sarah E; Marten, Jonathan; Rudan, Igor; Enroth, Stefan; Gyllensten, Ulf ...; Kerr, Shona M; Polasek, Ozren; Kähönen, Mika; Surakka, Ida; Vitart, Veroniqu ...; Hayward, Carolin ...; Lehtimäki, Terho; Raitakari, Olli ...; Evans, David M; Henderson, A Joh ...; Pennell, Craig E; Wang, Carol A; Sly, Peter D; Wan, Emily S; Busch, Robert; Hobbs, Brian D; Litonjua, August ...; Sparrow, David W; Gulsvik, Amund; Bakke, Per S; Crapo, James D; Beaty, Terri H; Hansel, Nadia N; Mathias, Rasika ...; Ruczinski, Ingo; Barnes, Kathleen ...; Bossé, Yohan; Joubert, Philipp ...; van den Berge, M ...; Brandsma, Corry- ...; Paré, Peter D; Sin, Don D; Nickle, David C; Hao, Ke; Gottesman, Omri; Dewey, Frederick ...; Bruse, Shannon E; Carey, David J; Kirchner, H Lest ...; Jonsson, Stefan; Thorleifsson, Gu ...; Jonsdottir, Ingi ...; Gislason, Thorar ...; Stefansson, Kari; Schurmann, Claud ...; Nadkarni, Girish; Bottinger, Erwin ...; Loos, Ruth J F; Walters, Robin G; Chen, Zhengming; Millwood, Iona Y; Vaucher, Julien; Kurmi, Om P; Li, Liming; Hansell, Anna L; Brightling, Chri ...; Zeggini, Elefthe ...; Cho, Michael H; Silverman, Edwin ...; Sayers, Ian; Trynka, Gosia; Morris, Andrew P; Strachan, David ...; Hall, Ian P; Tobin, Martin D; show less...

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