title: Replication and fine mapping of asthma-associated loci in individuals of African ancestry.
abstract: Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.
authors.affiliation: Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. david.kantor@childrens.harvard.edu
authors.forename: David B
authors.initials: DB
authors.lastname: Kantor
authors.forename: Cameron D
authors.initials: CD
authors.lastname: Palmer
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Young
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Zofia K
authors.initials: ZK
authors.lastname: Gajdos
authors.forename: Helen
authors.initials: H
authors.lastname: Lyon
authors.forename: Alkes L
authors.initials: AL
authors.lastname: Price
authors.forename: Samuela
authors.initials: S
authors.lastname: Pollack
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.forename: Laura R
authors.initials: LR
authors.lastname: Loehr
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Smith
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.forename: David R
authors.initials: DR
authors.lastname: Jacobs
authors.forename: Marcy F
authors.initials: MF
authors.lastname: Petrini
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.forename: Wendy B
authors.initials: WB
authors.lastname: White
authors.forename: George
authors.initials: G
authors.lastname: Papanicolaou
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Burkart
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
mesh_terms: D017766:Acid Anhydride Hydrolases; D001249:Asthma / Q000208:ethnology / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics; D053724:Receptors, Interleukin-18 / Q000235:genetics; D001741:Black or African American; D000094524:Gasdermins
chemical_list: D017766:Acid Anhydride Hydrolases; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D018793:Interleukin-13; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D017472:Receptors, Interleukin-1; D053724:Receptors, Interleukin-18; C527978:GSDMB protein, human; D000094524:Gasdermins; C464399:ORMDL3 protein, human; C112158:RAD50 protein, human