Dataset Information

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

ABSTRACT: 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.

SUBMITTER: Demenais F

PROVIDER: S-EPMC5901974 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

Demenais Florence F Margaritte-Jeannin Patricia P Barnes Kathleen C KC Cookson William O C WOC Altmüller Janine J Ang Wei W Barr R Graham RG Beaty Terri H TH Becker Allan B AB Beilby John J Bisgaard Hans H Bjornsdottir Unnur Steina US Bleecker Eugene E Bønnelykke Klaus K Boomsma Dorret I DI Bouzigon Emmanuelle E Brightling Christopher E CE Brossard Myriam M Brusselle Guy G GG Burchard Esteban E Burkart Kristin M KM Bush Andrew A Chan-Yeung Moira M Chung Kian Fan KF Couto Alves Alexessander A Curtin John A JA Custovic Adnan A Daley Denise D de Jongste Johan C JC Del-Rio-Navarro Blanca E BE Donohue Kathleen M KM Duijts Liesbeth L Eng Celeste C Eriksson Johan G JG Farrall Martin M Fedorova Yuliya Y Feenstra Bjarke B Ferreira Manuel A MA Freidin Maxim B MB Gajdos Zofia Z Gauderman Jim J Gehring Ulrike U Geller Frank F Genuneit Jon J Gharib Sina A SA Gilliland Frank F Granell Raquel R Graves Penelope E PE Gudbjartsson Daniel F DF Haahtela Tari T Heckbert Susan R SR Heederik Dick D Heinrich Joachim J Heliövaara Markku M Henderson John J Himes Blanca E BE Hirose Hiroshi H Hirschhorn Joel N JN Hofman Albert A Holt Patrick P Hottenga Jouke J Hudson Thomas J TJ Hui Jennie J Imboden Medea M Ivanov Vladimir V Jaddoe Vincent W V VWV James Alan A Janson Christer C Jarvelin Marjo-Riitta MR Jarvis Deborah D Jones Graham G Jonsdottir Ingileif I Jousilahti Pekka P Kabesch Michael M Kähönen Mika M Kantor David B DB Karunas Alexandra S AS Khusnutdinova Elza E Koppelman Gerard H GH Kozyrskyj Anita L AL Kreiner Eskil E Kubo Michiaki M Kumar Rajesh R Kumar Ashish A Kuokkanen Mikko M Lahousse Lies L Laitinen Tarja T Laprise Catherine C Lathrop Mark M Lau Susanne S Lee Young-Ae YA Lehtimäki Terho T Letort Sébastien S Levin Albert M AM Li Guo G Liang Liming L Loehr Laura R LR London Stephanie J SJ Loth Daan W DW Manichaikul Ani A Marenholz Ingo I Martinez Fernando J FJ Matheson Melanie C MC Mathias Rasika A RA Matsumoto Kenji K Mbarek Hamdi H McArdle Wendy L WL Melbye Mads M Melén Erik E Meyers Deborah D Michel Sven S Mohamdi Hamida H Musk Arthur W AW Myers Rachel A RA Nieuwenhuis Maartje A E MAE Noguchi Emiko E O'Connor George T GT Ogorodova Ludmila M LM Palmer Cameron D CD Palotie Aarno A Park Julie E JE Pennell Craig E CE Pershagen Göran G Polonikov Alexey A Postma Dirkje S DS Probst-Hensch Nicole N Puzyrev Valery P VP Raby Benjamin A BA Raitakari Olli T OT Ramasamy Adaikalavan A Rich Stephen S SS Robertson Colin F CF Romieu Isabelle I Salam Muhammad T MT Salomaa Veikko V Schlünssen Vivi V Scott Robert R Selivanova Polina A PA Sigsgaard Torben T Simpson Angela A Siroux Valérie V Smith Lewis J LJ Solodilova Maria M Standl Marie M Stefansson Kari K Strachan David P DP Stricker Bruno H BH Takahashi Atsushi A Thompson Philip J PJ Thorleifsson Gudmar G Thorsteinsdottir Unnur U Tiesler Carla M T CMT Torgerson Dara G DG Tsunoda Tatsuhiko T Uitterlinden André G AG van der Valk Ralf J P RJP Vaysse Amaury A Vedantam Sailaja S von Berg Andrea A von Mutius Erika E Vonk Judith M JM Waage Johannes J Wareham Nick J NJ Weiss Scott T ST White Wendy B WB Wickman Magnus M Widén Elisabeth E Willemsen Gonneke G Williams L Keoki LK Wouters Inge M IM Yang James J JJ Zhao Jing Hua JH Moffatt Miriam F MF Ober Carole C Nicolae Dan L DL

Nature genetics 20171222 1

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 i ...[more]

PMID: 29273806

Similar Datasets

Project description:BackgroundCalcific aortic stenosis (CAS) is the most common valvular heart disease in older adults and has no effective preventive therapies. Genome-wide association studies (GWAS) can identify genes influencing disease and may help prioritize therapeutic targets for CAS.MethodsWe performed a GWAS and gene association study of 14 451 patients with CAS and 398 544 controls in the Million Veteran Program. Replication was performed in the Million Veteran Program, Penn Medicine Biobank, Mass General Brigham Biobank, BioVU, and BioMe, totaling 12 889 cases and 348 094 controls. Causal genes were prioritized from genome-wide significant variants using polygenic priority score gene localization, expression quantitative trait locus colocalization, and nearest gene methods. CAS genetic architecture was compared with that of atherosclerotic cardiovascular disease. Causal inference for cardiometabolic biomarkers in CAS was performed using Mendelian randomization and genome-wide significant loci were characterized further through phenome-wide association study.ResultsWe identified 23 genome-wide significant lead variants in our GWAS representing 17 unique genomic regions. Of the 23 lead variants, 14 were significant in replication, representing 11 unique genomic regions. Five replicated genomic regions were previously known risk loci for CAS (PALMD, TEX41, IL6, LPA, FADS) and 6 were novel (CEP85L, FTO, SLMAP, CELSR2, MECOM, CDAN1). Two novel lead variants were associated in non-White individuals (P<0.05): rs12740374 (CELSR2) in Black and Hispanic individuals and rs1522387 (SLMAP) in Black individuals. Of the 14 replicated lead variants, only 2 (rs10455872 [LPA], rs12740374 [CELSR2]) were also significant in atherosclerotic cardiovascular disease GWAS. In Mendelian randomization, lipoprotein(a) and low-density lipoprotein cholesterol were both associated with CAS, but the association between low-density lipoprotein cholesterol and CAS was attenuated when adjusting for lipoprotein(a). Phenome-wide association study highlighted varying degrees of pleiotropy, including between CAS and obesity at the FTO locus. However, the FTO locus remained associated with CAS after adjusting for body mass index and maintained a significant independent effect on CAS in mediation analysis.ConclusionsWe performed a multiancestry GWAS in CAS and identified 6 novel genomic regions in the disease. Secondary analyses highlighted the roles of lipid metabolism, inflammation, cellular senescence, and adiposity in the pathobiology of CAS and clarified the shared and differential genetic architectures of CAS with atherosclerotic cardiovascular diseases.

Dataset Information

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

Publications

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets