Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.
Demenais F., Margaritte-Jeannin P., Barnes KC., Cookson WOC., Altmüller J., Ang W., Barr RG., Beaty TH., Becker AB., Beilby J., Bisgaard H., Bjornsdottir US., Bleecker E., Bønnelykke K., Boomsma DI., Bouzigon E., Brightling CE., Brossard M., Brusselle GG., Burchard E., Burkart KM., Bush A., Chan-Yeung M., Chung KF., Couto Alves A., Curtin JA., Custovic A., Daley D., de Jongste JC., Del-Rio-Navarro BE., Donohue KM., Duijts L., Eng C., Eriksson JG., Farrall M., Fedorova Y., Feenstra B., Ferreira MA., Australian Asthma Genetics Consortium (AAGC) collaborators None., Freidin MB., Gajdos Z., Gauderman J., Gehring U., Geller F., Genuneit J., Gharib SA., Gilliland F., Granell R., Graves PE., Gudbjartsson DF., Haahtela T., Heckbert SR., Heederik D., Heinrich J., Heliövaara M., Henderson J., Himes BE., Hirose H., Hirschhorn JN., Hofman A., Holt P., Hottenga J., Hudson TJ., Hui J., Imboden M., Ivanov V., Jaddoe VWV., James A., Janson C., Jarvelin M-R., Jarvis D., Jones G., Jonsdottir I., Jousilahti P., Kabesch M., Kähönen M., Kantor DB., Karunas AS., Khusnutdinova E., Koppelman GH., Kozyrskyj AL., Kreiner E., Kubo M., Kumar R., Kumar A., Kuokkanen M., Lahousse L., Laitinen T., Laprise C., Lathrop M., Lau S., Lee Y-A., Lehtimäki T., Letort S., Levin AM., Li G., Liang L., Loehr LR., London SJ., Loth DW., Manichaikul A., Marenholz I., Martinez FJ., Matheson MC., Mathias RA., Matsumoto K., Mbarek H., McArdle WL., Melbye M., Melén E., Meyers D., Michel S., Mohamdi H., Musk AW., Myers RA., Nieuwenhuis MAE., Noguchi E., O'Connor GT., Ogorodova LM., Palmer CD., Palotie A., Park JE., Pennell CE., Pershagen G., Polonikov A., Postma DS., Probst-Hensch N., Puzyrev VP., Raby BA., Raitakari OT., Ramasamy A., Rich SS., Robertson CF., Romieu I., Salam MT., Salomaa V., Schlünssen V., Scott R., Selivanova PA., Sigsgaard T., Simpson A., Siroux V., Smith LJ., Solodilova M., Standl M., Stefansson K., Strachan DP., Stricker BH., Takahashi A., Thompson PJ., Thorleifsson G., Thorsteinsdottir U., Tiesler CMT., Torgerson DG., Tsunoda T., Uitterlinden AG., van der Valk RJP., Vaysse A., Vedantam S., von Berg A., von Mutius E., Vonk JM., Waage J., Wareham NJ., Weiss ST., White WB., Wickman M., Widén E., Willemsen G., Williams LK., Wouters IM., Yang JJ., Zhao JH., Moffatt MF., Ober C., Nicolae DL.
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.