Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.
<h4>Rationale</h4>Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.<h4>Objectives</h4>To test if population-based cohorts with self-reported physician-diagn...
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2012-01-01
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| author | Adaikalavan Ramasamy Mikko Kuokkanen Sailaja Vedantam Zofia K Gajdos Alexessander Couto Alves Helen N Lyon Manuel A R Ferreira David P Strachan Jing Hua Zhao Michael J Abramson Matthew A Brown Lachlan Coin Shyamali C Dharmage David L Duffy Tari Haahtela Andrew C Heath Christer Janson Mika Kähönen Kay-Tee Khaw Jaana Laitinen Peter Le Souef Terho Lehtimäki Australian Asthma Genetics Consortium Collaborators Pamela A F Madden Guy B Marks Nicholas G Martin Melanie C Matheson Cameron D Palmer Aarno Palotie Anneli Pouta Colin F Robertson Jorma Viikari Elisabeth Widen Matthias Wjst Deborah L Jarvis Grant W Montgomery Philip J Thompson Nick Wareham Johan Eriksson Pekka Jousilahti Tarja Laitinen Juha Pekkanen Olli T Raitakari George T O'Connor Veikko Salomaa Marjo-Riitta Jarvelin Joel N Hirschhorn |
| author_facet | Adaikalavan Ramasamy Mikko Kuokkanen Sailaja Vedantam Zofia K Gajdos Alexessander Couto Alves Helen N Lyon Manuel A R Ferreira David P Strachan Jing Hua Zhao Michael J Abramson Matthew A Brown Lachlan Coin Shyamali C Dharmage David L Duffy Tari Haahtela Andrew C Heath Christer Janson Mika Kähönen Kay-Tee Khaw Jaana Laitinen Peter Le Souef Terho Lehtimäki Australian Asthma Genetics Consortium Collaborators Pamela A F Madden Guy B Marks Nicholas G Martin Melanie C Matheson Cameron D Palmer Aarno Palotie Anneli Pouta Colin F Robertson Jorma Viikari Elisabeth Widen Matthias Wjst Deborah L Jarvis Grant W Montgomery Philip J Thompson Nick Wareham Johan Eriksson Pekka Jousilahti Tarja Laitinen Juha Pekkanen Olli T Raitakari George T O'Connor Veikko Salomaa Marjo-Riitta Jarvelin Joel N Hirschhorn |
| author_sort | Adaikalavan Ramasamy |
| collection | DOAJ |
| description | <h4>Rationale</h4>Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.<h4>Objectives</h4>To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations.<h4>Methods</h4>The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5 x 10(-8)) and three variants reported as suggestive (P<5× 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever.<h4>Main results</h4>We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4 × 10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P(Stage1+Stage2) = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P(Stage1+Stage2) = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status.<h4>Conclusions</h4>Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma. |
| format | Article |
| id | doaj-art-c816652d63b14f159aa85ccbfad1b788 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c816652d63b14f159aa85ccbfad1b7882025-08-20T03:09:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4400810.1371/journal.pone.0044008Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.Adaikalavan RamasamyMikko KuokkanenSailaja VedantamZofia K GajdosAlexessander Couto AlvesHelen N LyonManuel A R FerreiraDavid P StrachanJing Hua ZhaoMichael J AbramsonMatthew A BrownLachlan CoinShyamali C DharmageDavid L DuffyTari HaahtelaAndrew C HeathChrister JansonMika KähönenKay-Tee KhawJaana LaitinenPeter Le SouefTerho LehtimäkiAustralian Asthma Genetics Consortium CollaboratorsPamela A F MaddenGuy B MarksNicholas G MartinMelanie C MathesonCameron D PalmerAarno PalotieAnneli PoutaColin F RobertsonJorma ViikariElisabeth WidenMatthias WjstDeborah L JarvisGrant W MontgomeryPhilip J ThompsonNick WarehamJohan ErikssonPekka JousilahtiTarja LaitinenJuha PekkanenOlli T RaitakariGeorge T O'ConnorVeikko SalomaaMarjo-Riitta JarvelinJoel N Hirschhorn<h4>Rationale</h4>Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.<h4>Objectives</h4>To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations.<h4>Methods</h4>The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5 x 10(-8)) and three variants reported as suggestive (P<5× 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever.<h4>Main results</h4>We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4 × 10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P(Stage1+Stage2) = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P(Stage1+Stage2) = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status.<h4>Conclusions</h4>Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0044008&type=printable |
| spellingShingle | Adaikalavan Ramasamy Mikko Kuokkanen Sailaja Vedantam Zofia K Gajdos Alexessander Couto Alves Helen N Lyon Manuel A R Ferreira David P Strachan Jing Hua Zhao Michael J Abramson Matthew A Brown Lachlan Coin Shyamali C Dharmage David L Duffy Tari Haahtela Andrew C Heath Christer Janson Mika Kähönen Kay-Tee Khaw Jaana Laitinen Peter Le Souef Terho Lehtimäki Australian Asthma Genetics Consortium Collaborators Pamela A F Madden Guy B Marks Nicholas G Martin Melanie C Matheson Cameron D Palmer Aarno Palotie Anneli Pouta Colin F Robertson Jorma Viikari Elisabeth Widen Matthias Wjst Deborah L Jarvis Grant W Montgomery Philip J Thompson Nick Wareham Johan Eriksson Pekka Jousilahti Tarja Laitinen Juha Pekkanen Olli T Raitakari George T O'Connor Veikko Salomaa Marjo-Riitta Jarvelin Joel N Hirschhorn Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. PLoS ONE |
| title | Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. |
| title_full | Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. |
| title_fullStr | Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. |
| title_full_unstemmed | Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. |
| title_short | Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. |
| title_sort | genome wide association studies of asthma in population based cohorts confirm known and suggested loci and identify an additional association near hla |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0044008&type=printable |
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