TY - JOUR T1 - Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. JF - Nat Genet Y1 - 2011 A1 - Soler Artigas, Maria A1 - Loth, Daan W A1 - Wain, Louise V A1 - Gharib, Sina A A1 - Obeidat, Ma'en A1 - Tang, Wenbo A1 - Zhai, Guangju A1 - Zhao, Jing Hua A1 - Smith, Albert Vernon A1 - Huffman, Jennifer E A1 - Albrecht, Eva A1 - Jackson, Catherine M A1 - Evans, David M A1 - Cadby, Gemma A1 - Fornage, Myriam A1 - Manichaikul, Ani A1 - Lopez, Lorna M A1 - Johnson, Toby A1 - Aldrich, Melinda C A1 - Aspelund, Thor A1 - Barroso, Inês A1 - Campbell, Harry A1 - Cassano, Patricia A A1 - Couper, David J A1 - Eiriksdottir, Gudny A1 - Franceschini, Nora A1 - Garcia, Melissa A1 - Gieger, Christian A1 - Gislason, Gauti Kjartan A1 - Grkovic, Ivica A1 - Hammond, Christopher J A1 - Hancock, Dana B A1 - Harris, Tamara B A1 - Ramasamy, Adaikalavan A1 - Heckbert, Susan R A1 - Heliövaara, Markku A1 - Homuth, Georg A1 - Hysi, Pirro G A1 - James, Alan L A1 - Jankovic, Stipan A1 - Joubert, Bonnie R A1 - Karrasch, Stefan A1 - Klopp, Norman A1 - Koch, Beate A1 - Kritchevsky, Stephen B A1 - Launer, Lenore J A1 - Liu, Yongmei A1 - Loehr, Laura R A1 - Lohman, Kurt A1 - Loos, Ruth J F A1 - Lumley, Thomas A1 - Al Balushi, Khalid A A1 - Ang, Wei Q A1 - Barr, R Graham A1 - Beilby, John A1 - Blakey, John D A1 - Boban, Mladen A1 - Boraska, Vesna A1 - Brisman, Jonas A1 - Britton, John R A1 - Brusselle, Guy G A1 - Cooper, Cyrus A1 - Curjuric, Ivan A1 - Dahgam, Santosh A1 - Deary, Ian J A1 - Ebrahim, Shah A1 - Eijgelsheim, Mark A1 - Francks, Clyde A1 - Gaysina, Darya A1 - Granell, Raquel A1 - Gu, Xiangjun A1 - Hankinson, John L A1 - Hardy, Rebecca A1 - Harris, Sarah E A1 - Henderson, John A1 - Henry, Amanda A1 - Hingorani, Aroon D A1 - Hofman, Albert A1 - Holt, Patrick G A1 - Hui, Jennie A1 - Hunter, Michael L A1 - Imboden, Medea A1 - Jameson, Karen A A1 - Kerr, Shona M A1 - Kolcic, Ivana A1 - Kronenberg, Florian A1 - Liu, Jason Z A1 - Marchini, Jonathan A1 - McKeever, Tricia A1 - Morris, Andrew D A1 - Olin, Anna-Carin A1 - Porteous, David J A1 - Postma, Dirkje S A1 - Rich, Stephen S A1 - Ring, Susan M A1 - Rivadeneira, Fernando A1 - Rochat, Thierry A1 - Sayer, Avan Aihie A1 - Sayers, Ian A1 - Sly, Peter D A1 - Smith, George Davey A1 - Sood, Akshay A1 - Starr, John M A1 - Uitterlinden, André G A1 - Vonk, Judith M A1 - Wannamethee, S Goya A1 - Whincup, Peter H A1 - Wijmenga, Cisca A1 - Williams, O Dale A1 - Wong, Andrew A1 - Mangino, Massimo A1 - Marciante, Kristin D A1 - McArdle, Wendy L A1 - Meibohm, Bernd A1 - Morrison, Alanna C A1 - North, Kari E A1 - Omenaas, Ernst A1 - Palmer, Lyle J A1 - Pietiläinen, Kirsi H A1 - Pin, Isabelle A1 - Pola Sbreve Ek, Ozren A1 - Pouta, Anneli A1 - Psaty, Bruce M A1 - Hartikainen, Anna-Liisa A1 - Rantanen, Taina A1 - Ripatti, Samuli A1 - Rotter, Jerome I A1 - Rudan, Igor A1 - Rudnicka, Alicja R A1 - Schulz, Holger A1 - Shin, So-Youn A1 - Spector, Tim D A1 - Surakka, Ida A1 - Vitart, Veronique A1 - Völzke, Henry A1 - Wareham, Nicholas J A1 - Warrington, Nicole M A1 - Wichmann, H-Erich A1 - Wild, Sarah H A1 - Wilk, Jemma B A1 - Wjst, Matthias A1 - Wright, Alan F A1 - Zgaga, Lina A1 - Zemunik, Tatijana A1 - Pennell, Craig E A1 - Nyberg, Fredrik A1 - Kuh, Diana A1 - Holloway, John W A1 - Boezen, H Marike A1 - Lawlor, Debbie A A1 - Morris, Richard W A1 - Probst-Hensch, Nicole A1 - Kaprio, Jaakko A1 - Wilson, James F A1 - Hayward, Caroline A1 - Kähönen, Mika A1 - Heinrich, Joachim A1 - Musk, Arthur W A1 - Jarvis, Deborah L A1 - Gläser, Sven A1 - Jarvelin, Marjo-Riitta A1 - Ch Stricker, Bruno H A1 - Elliott, Paul A1 - O'Connor, George T A1 - Strachan, David P A1 - London, Stephanie J A1 - Hall, Ian P A1 - Gudnason, Vilmundur A1 - Tobin, Martin D KW - Child KW - European Continental Ancestry Group KW - Genome-Wide Association Study KW - Humans KW - Pulmonary Disease, Chronic Obstructive KW - Respiratory Function Tests AB -

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

VL - 43 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21946350?dopt=Abstract ER - TY - JOUR T1 - Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction. JF - Am J Respir Crit Care Med Y1 - 2012 A1 - Wilk, Jemma B A1 - Shrine, Nick R G A1 - Loehr, Laura R A1 - Zhao, Jing Hua A1 - Manichaikul, Ani A1 - Lopez, Lorna M A1 - Smith, Albert Vernon A1 - Heckbert, Susan R A1 - Smolonska, Joanna A1 - Tang, Wenbo A1 - Loth, Daan W A1 - Curjuric, Ivan A1 - Hui, Jennie A1 - Cho, Michael H A1 - Latourelle, Jeanne C A1 - Henry, Amanda P A1 - Aldrich, Melinda A1 - Bakke, Per A1 - Beaty, Terri H A1 - Bentley, Amy R A1 - Borecki, Ingrid B A1 - Brusselle, Guy G A1 - Burkart, Kristin M A1 - Chen, Ting-Hsu A1 - Couper, David A1 - Crapo, James D A1 - Davies, Gail A1 - Dupuis, Josée A1 - Franceschini, Nora A1 - Gulsvik, Amund A1 - Hancock, Dana B A1 - Harris, Tamara B A1 - Hofman, Albert A1 - Imboden, Medea A1 - James, Alan L A1 - Khaw, Kay-Tee A1 - Lahousse, Lies A1 - Launer, Lenore J A1 - Litonjua, Augusto A1 - Liu, Yongmei A1 - Lohman, Kurt K A1 - Lomas, David A A1 - Lumley, Thomas A1 - Marciante, Kristin D A1 - McArdle, Wendy L A1 - Meibohm, Bernd A1 - Morrison, Alanna C A1 - Musk, Arthur W A1 - Myers, Richard H A1 - North, Kari E A1 - Postma, Dirkje S A1 - Psaty, Bruce M A1 - Rich, Stephen S A1 - Rivadeneira, Fernando A1 - Rochat, Thierry A1 - Rotter, Jerome I A1 - Soler Artigas, Maria A1 - Starr, John M A1 - Uitterlinden, André G A1 - Wareham, Nicholas J A1 - Wijmenga, Cisca A1 - Zanen, Pieter A1 - Province, Michael A A1 - Silverman, Edwin K A1 - Deary, Ian J A1 - Palmer, Lyle J A1 - Cassano, Patricia A A1 - Gudnason, Vilmundur A1 - Barr, R Graham A1 - Loos, Ruth J F A1 - Strachan, David P A1 - London, Stephanie J A1 - Boezen, H Marike A1 - Probst-Hensch, Nicole A1 - Gharib, Sina A A1 - Hall, Ian P A1 - O'Connor, George T A1 - Tobin, Martin D A1 - Stricker, Bruno H KW - Aged KW - Female KW - Forced Expiratory Volume KW - Genome-Wide Association Study KW - Humans KW - Male KW - Middle Aged KW - Nerve Tissue Proteins KW - Polymorphism, Single Nucleotide KW - Pulmonary Disease, Chronic Obstructive KW - Receptors, Nicotinic KW - Receptors, Serotonin, 5-HT4 KW - Smoking KW - Vital Capacity AB -

RATIONALE: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.

OBJECTIVES: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases.

METHODS: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV(1) and its ratio to FVC (FEV(1)/FVC) both less than their respective lower limits of normal as determined by published reference equations.

MEASUREMENTS AND MAIN RESULTS: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV(1)/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis.

CONCLUSIONS: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction.

VL - 186 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22837378?dopt=Abstract ER - TY - JOUR T1 - Integrative pathway genomics of lung function and airflow obstruction. JF - Hum Mol Genet Y1 - 2015 A1 - Gharib, Sina A A1 - Loth, Daan W A1 - Soler Artigas, Maria A1 - Birkland, Timothy P A1 - Wilk, Jemma B A1 - Wain, Louise V A1 - Brody, Jennifer A A1 - Obeidat, Ma'en A1 - Hancock, Dana B A1 - Tang, Wenbo A1 - Rawal, Rajesh A1 - Boezen, H Marike A1 - Imboden, Medea A1 - Huffman, Jennifer E A1 - Lahousse, Lies A1 - Alves, Alexessander C A1 - Manichaikul, Ani A1 - Hui, Jennie A1 - Morrison, Alanna C A1 - Ramasamy, Adaikalavan A1 - Smith, Albert Vernon A1 - Gudnason, Vilmundur A1 - Surakka, Ida A1 - Vitart, Veronique A1 - Evans, David M A1 - Strachan, David P A1 - Deary, Ian J A1 - Hofman, Albert A1 - Gläser, Sven A1 - Wilson, James F A1 - North, Kari E A1 - Zhao, Jing Hua A1 - Heckbert, Susan R A1 - Jarvis, Deborah L A1 - Probst-Hensch, Nicole A1 - Schulz, Holger A1 - Barr, R Graham A1 - Jarvelin, Marjo-Riitta A1 - O'Connor, George T A1 - Kähönen, Mika A1 - Cassano, Patricia A A1 - Hysi, Pirro G A1 - Dupuis, Josée A1 - Hayward, Caroline A1 - Psaty, Bruce M A1 - Hall, Ian P A1 - Parks, William C A1 - Tobin, Martin D A1 - London, Stephanie J KW - Airway Obstruction KW - Animals KW - Cell Proliferation KW - European Continental Ancestry Group KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Genomics KW - Humans KW - Immune System KW - Lung KW - Male KW - Metabolic Networks and Pathways KW - Mice KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Signal Transduction AB -

Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating pathway-based methods with GWASs of pulmonary function and airflow obstruction would identify a broader repertoire of genes and processes influencing these traits. We performed two independent GWASs of lung function and applied gene set enrichment analysis to one of the studies and validated the results using the second GWAS. We identified 131 significantly enriched gene sets associated with lung function and clustered them into larger biological modules involved in diverse processes including development, immunity, cell signaling, proliferation and arachidonic acid. We found that enrichment of gene sets was not driven by GWAS-significant variants or loci, but instead by those with less stringent association P-values. Next, we applied pathway enrichment analysis to a meta-analyzed GWAS of airflow obstruction. We identified several biologic modules that functionally overlapped with those associated with pulmonary function. However, differences were also noted, including enrichment of extracellular matrix (ECM) processes specifically in the airflow obstruction study. Network analysis of the ECM module implicated a candidate gene, matrix metalloproteinase 10 (MMP10), as a putative disease target. We used a knockout mouse model to functionally validate MMP10's role in influencing lung's susceptibility to cigarette smoke-induced emphysema. By integrating pathway analysis with population-based genomics, we unraveled biologic processes underlying pulmonary function traits and identified a candidate gene for obstructive lung disease.

VL - 24 IS - 23 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26395457?dopt=Abstract ER - TY - JOUR T1 - Meta-analysis of exome array data identifies six novel genetic loci for lung function. JF - Wellcome Open Res Y1 - 2018 A1 - Jackson, Victoria E A1 - Latourelle, Jeanne C A1 - Wain, Louise V A1 - Smith, Albert V A1 - Grove, Megan L A1 - Bartz, Traci M A1 - Obeidat, Ma'en A1 - Province, Michael A A1 - Gao, Wei A1 - Qaiser, Beenish A1 - Porteous, David J A1 - Cassano, Patricia A A1 - Ahluwalia, Tarunveer S A1 - Grarup, Niels A1 - Li, Jin A1 - Altmaier, Elisabeth A1 - Marten, Jonathan A1 - Harris, Sarah E A1 - Manichaikul, Ani A1 - Pottinger, Tess D A1 - Li-Gao, Ruifang A1 - Lind-Thomsen, Allan A1 - Mahajan, Anubha A1 - Lahousse, Lies A1 - Imboden, Medea A1 - Teumer, Alexander A1 - Prins, Bram A1 - Lyytikäinen, Leo-Pekka A1 - Eiriksdottir, Gudny A1 - Franceschini, Nora A1 - Sitlani, Colleen M A1 - Brody, Jennifer A A1 - Bossé, Yohan A1 - Timens, Wim A1 - Kraja, Aldi A1 - Loukola, Anu A1 - Tang, Wenbo A1 - Liu, Yongmei A1 - Bork-Jensen, Jette A1 - Justesen, Johanne M A1 - Linneberg, Allan A1 - Lange, Leslie A A1 - Rawal, Rajesh A1 - Karrasch, Stefan A1 - Huffman, Jennifer E A1 - Smith, Blair H A1 - Davies, Gail A1 - Burkart, Kristin M A1 - Mychaleckyj, Josyf C A1 - Bonten, Tobias N A1 - Enroth, Stefan A1 - Lind, Lars A1 - Brusselle, Guy G A1 - Kumar, Ashish A1 - Stubbe, Beate A1 - Kähönen, Mika A1 - Wyss, Annah B A1 - Psaty, Bruce M A1 - Heckbert, Susan R A1 - Hao, Ke A1 - Rantanen, Taina A1 - Kritchevsky, Stephen B A1 - Lohman, Kurt A1 - Skaaby, Tea A1 - Pisinger, Charlotta A1 - Hansen, Torben A1 - Schulz, Holger A1 - Polasek, Ozren A1 - Campbell, Archie A1 - Starr, John M A1 - Rich, Stephen S A1 - Mook-Kanamori, Dennis O A1 - Johansson, Asa A1 - Ingelsson, Erik A1 - Uitterlinden, André G A1 - Weiss, Stefan A1 - Raitakari, Olli T A1 - Gudnason, Vilmundur A1 - North, Kari E A1 - Gharib, Sina A A1 - Sin, Don D A1 - Taylor, Kent D A1 - O'Connor, George T A1 - Kaprio, Jaakko A1 - Harris, Tamara B A1 - Pederson, Oluf A1 - Vestergaard, Henrik A1 - Wilson, James G A1 - Strauch, Konstantin A1 - Hayward, Caroline A1 - Kerr, Shona A1 - Deary, Ian J A1 - Barr, R Graham A1 - de Mutsert, Renée A1 - Gyllensten, Ulf A1 - Morris, Andrew P A1 - Ikram, M Arfan A1 - Probst-Hensch, Nicole A1 - Gläser, Sven A1 - Zeggini, Eleftheria A1 - Lehtimäki, Terho A1 - Strachan, David P A1 - Dupuis, Josée A1 - Morrison, Alanna C A1 - Hall, Ian P A1 - Tobin, Martin D A1 - London, Stephanie J AB -

Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV ), forced vital capacity (FVC) and the ratio of FEV to FVC (FEV /FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. We identified significant (P<2·8x10 ) associations with six SNPs: a nonsynonymous variant in , which is predicted to be damaging, three intronic SNPs ( and ) and two intergenic SNPs near to and Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including and . Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

VL - 3 ER - TY - JOUR T1 - Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. JF - Nat Genet Y1 - 2018 A1 - Demenais, Florence A1 - Margaritte-Jeannin, Patricia A1 - Barnes, Kathleen C A1 - Cookson, William O C A1 - Altmüller, Janine A1 - Ang, Wei A1 - Barr, R Graham A1 - Beaty, Terri H A1 - Becker, Allan B A1 - Beilby, John A1 - Bisgaard, Hans A1 - Bjornsdottir, Unnur Steina A1 - Bleecker, Eugene A1 - Bønnelykke, Klaus A1 - Boomsma, Dorret I A1 - Bouzigon, Emmanuelle A1 - Brightling, Christopher E A1 - Brossard, Myriam A1 - Brusselle, Guy G A1 - Burchard, Esteban A1 - Burkart, Kristin M A1 - Bush, Andrew A1 - Chan-Yeung, Moira A1 - Chung, Kian Fan A1 - Couto Alves, Alexessander A1 - Curtin, John A A1 - Custovic, Adnan A1 - Daley, Denise A1 - de Jongste, Johan C A1 - Del-Rio-Navarro, Blanca E A1 - Donohue, Kathleen M A1 - Duijts, Liesbeth A1 - Eng, Celeste A1 - Eriksson, Johan G A1 - Farrall, Martin A1 - Fedorova, Yuliya A1 - Feenstra, Bjarke A1 - Ferreira, Manuel A A1 - Freidin, Maxim B A1 - Gajdos, Zofia A1 - Gauderman, Jim A1 - Gehring, Ulrike A1 - Geller, Frank A1 - Genuneit, Jon A1 - Gharib, Sina A A1 - Gilliland, Frank A1 - Granell, Raquel A1 - Graves, Penelope E A1 - Gudbjartsson, Daniel F A1 - Haahtela, Tari A1 - Heckbert, Susan R A1 - Heederik, Dick A1 - Heinrich, Joachim A1 - Heliövaara, Markku A1 - Henderson, John A1 - Himes, Blanca E A1 - Hirose, Hiroshi A1 - Hirschhorn, Joel N A1 - Hofman, Albert A1 - Holt, Patrick A1 - Hottenga, Jouke A1 - Hudson, Thomas J A1 - Hui, Jennie A1 - Imboden, Medea A1 - Ivanov, Vladimir A1 - Jaddoe, Vincent W V A1 - James, Alan A1 - Janson, Christer A1 - Jarvelin, Marjo-Riitta A1 - Jarvis, Deborah A1 - Jones, Graham A1 - Jonsdottir, Ingileif A1 - Jousilahti, Pekka A1 - Kabesch, Michael A1 - Kähönen, Mika A1 - Kantor, David B A1 - Karunas, Alexandra S A1 - Khusnutdinova, Elza A1 - Koppelman, Gerard H A1 - Kozyrskyj, Anita L A1 - Kreiner, Eskil A1 - Kubo, Michiaki A1 - Kumar, Rajesh A1 - Kumar, Ashish A1 - Kuokkanen, Mikko A1 - Lahousse, Lies A1 - Laitinen, Tarja A1 - Laprise, Catherine A1 - Lathrop, Mark A1 - Lau, Susanne A1 - Lee, Young-Ae A1 - Lehtimäki, Terho A1 - Letort, Sébastien A1 - Levin, Albert M A1 - Li, Guo A1 - Liang, Liming A1 - Loehr, Laura R A1 - London, Stephanie J A1 - Loth, Daan W A1 - Manichaikul, Ani A1 - Marenholz, Ingo A1 - Martinez, Fernando J A1 - Matheson, Melanie C A1 - Mathias, Rasika A A1 - Matsumoto, Kenji A1 - Mbarek, Hamdi A1 - McArdle, Wendy L A1 - Melbye, Mads A1 - Melén, Erik A1 - Meyers, Deborah A1 - Michel, Sven A1 - Mohamdi, Hamida A1 - Musk, Arthur W A1 - Myers, Rachel A A1 - Nieuwenhuis, Maartje A E A1 - Noguchi, Emiko A1 - O'Connor, George T A1 - Ogorodova, Ludmila M A1 - Palmer, Cameron D A1 - Palotie, Aarno A1 - Park, Julie E A1 - Pennell, Craig E A1 - Pershagen, Göran A1 - Polonikov, Alexey A1 - Postma, Dirkje S A1 - Probst-Hensch, Nicole A1 - Puzyrev, Valery P A1 - Raby, Benjamin A A1 - Raitakari, Olli T A1 - Ramasamy, Adaikalavan A1 - Rich, Stephen S A1 - Robertson, Colin F A1 - Romieu, Isabelle A1 - Salam, Muhammad T A1 - Salomaa, Veikko A1 - Schlünssen, Vivi A1 - Scott, Robert A1 - Selivanova, Polina A A1 - Sigsgaard, Torben A1 - Simpson, Angela A1 - Siroux, Valérie A1 - Smith, Lewis J A1 - Solodilova, Maria A1 - Standl, Marie A1 - Stefansson, Kari A1 - Strachan, David P A1 - Stricker, Bruno H A1 - Takahashi, Atsushi A1 - Thompson, Philip J A1 - Thorleifsson, Gudmar A1 - Thorsteinsdottir, Unnur A1 - Tiesler, Carla M T A1 - Torgerson, Dara G A1 - Tsunoda, Tatsuhiko A1 - Uitterlinden, André G A1 - van der Valk, Ralf J P A1 - Vaysse, Amaury A1 - Vedantam, Sailaja A1 - von Berg, Andrea A1 - von Mutius, Erika A1 - Vonk, Judith M A1 - Waage, Johannes A1 - Wareham, Nick J A1 - Weiss, Scott T A1 - White, Wendy B A1 - Wickman, Magnus A1 - Widen, Elisabeth A1 - Willemsen, Gonneke A1 - Williams, L Keoki A1 - Wouters, Inge M A1 - Yang, James J A1 - Zhao, Jing Hua A1 - Moffatt, Miriam F A1 - Ober, Carole A1 - Nicolae, Dan L AB -

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

VL - 50 IS - 1 ER -