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Replication and fine mapping of asthma-associated loci in individuals of African ancestry.

TitleReplication and fine mapping of asthma-associated loci in individuals of African ancestry.
Publication TypeJournal Article
Year of Publication2013
AuthorsKantor DB, Palmer CD, Young TR, Meng Y, Gajdos ZK, Lyon H, Price AL, Pollack S, London SJ, Loehr LR, Smith LJ, Kumar R, Jacobs DR, Petrini MF, O'Connor GT, White WB, Papanicolaou G, Burkart KM, Heckbert SR, Barr GR
Secondary AuthorsHirschhorn JN
JournalHum Genet
Volume132
Issue9
Pagination1039-47
Date Published2013 Sep
ISSN1432-1203
KeywordsAfrican Continental Ancestry Group, Asthma, Chromosomes, Human, Pair 10, DNA Repair Enzymes, DNA-Binding Proteins, Female, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Interleukin-13, Male, Membrane Proteins, Neoplasm Proteins, Polymorphism, Single Nucleotide, Receptors, Interleukin-1, Receptors, Interleukin-18
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.

DOI10.1007/s00439-013-1310-7
Alternate JournalHum Genet
PubMed ID23666277
PubMed Central IDPMC3975655
Grant ListN01-HC-45205 / HC / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
HL100543 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01-HL093081 / HL / NHLBI NIH HHS / United States
N01-HC-95163 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-95168 / HC / NHLBI NIH HHS / United States
R01 HL077612 / HL / NHLBI NIH HHS / United States
R01 HG006399 / HG / NHGRI NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
RC1 HL100543 / HL / NHLBI NIH HHS / United States
N01-HC-95165 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
N01-HC- 95095 / HC / NHLBI NIH HHS / United States
R01-HL077612 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
N01-HC-95164 / HC / NHLBI NIH HHS / United States
R01-HL-071205 / HL / NHLBI NIH HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-95160 / HC / NHLBI NIH HHS / United States
N01-HC-95171 / HC / NHLBI NIH HHS / United States
N01-HC-95172 / HC / NHLBI NIH HHS / United States
T32 5T32HD040128-09 / HD / NICHD NIH HHS / United States
N01-HC-95161 / HC / NHLBI NIH HHS / United States
UL1 RR025758 / RR / NCRR NIH HHS / United States
N01-HC- 45204 / HC / NHLBI NIH HHS / United States
N01-HC-95100 / HC / NHLBI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01-HC-95166 / HC / NHLBI NIH HHS / United States
N01-HC-95170 / HC / NHLBI NIH HHS / United States
HHSN26800625226C / / PHS HHS / United States
N01-HC-95167 / HC / NHLBI NIH HHS / United States