title: Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects.
abstract: BACKGROUND
  Genetic variants that contribute to asthma susceptibility might be present at varying frequencies in different populations, which is an important consideration and advantage for performing genetic association studies in admixed populations.
  
  
  OBJECTIVE
  We sought to identify asthma-associated loci in African American subjects.
  
  
  METHODS
  We compared local African and European ancestry estimated from dense single nucleotide polymorphism genotype data in African American adults with asthma and nonasthmatic control subjects. Allelic tests of association were performed within the candidate regions identified, correcting for local European admixture.
  
  
  RESULTS
  We identified a significant ancestry association peak on chromosome 6q. Allelic tests for association within this region identified a single nucleotide polymorphism (rs1361549) on 6q14.1 that was associated with asthma exclusively in African American subjects with local European admixture (odds ratio, 2.2). The risk allele is common in Europe (42% in the HapMap population of Utah residents with Northern and Western European ancestry from the Centre d'Etude du Polymorphisme Humain collection) but absent in West Africa (0% in the HapMap population of Yorubans in Ibadan, Nigeria), suggesting the allele is present in African American subjects because of recent European admixture. We replicated our findings in Puerto Rican subjects and similarly found that the signal of association is largely specific to subjects who are heterozygous for African and non-African ancestry at 6q14.1. However, we found no evidence for association in European American or Puerto Rican subjects in the absence of local African ancestry, suggesting that the association with asthma at rs1361549 is due to an environmental or genetic interaction.
  
  
  CONCLUSIONS
  We identified a novel asthma-associated locus that is relevant to admixed populations with African ancestry and highlight the importance of considering local ancestry in genetic association studies of admixed populations.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Il 60637, USA.
authors.forename: Dara G
authors.initials: DG
authors.lastname: Torgerson
authors.forename: Daniel
authors.initials: D
authors.lastname: Capurso
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Ampleford
authors.forename: Xingnan
authors.initials: X
authors.lastname: Li
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gignoux
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fitzpatrick
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
authors.forename: José R
authors.initials: JR
authors.lastname: Rodríguez-Santana
authors.forename: William
authors.initials: W
authors.lastname: Rodríguez-Cintrón
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.forename: Jean G
authors.initials: JG
authors.lastname: Ford
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Howard
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.forename: Dan L
authors.initials: DL
authors.lastname: Nicolae
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001249:Asthma / Q000209:etiology / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics*