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Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

ABSTRACT: Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.

SUBMITTER: Daya M

PROVIDER: S-EPMC6382865 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Daya Michelle M Rafaels Nicholas N Brunetti Tonya M TM Chavan Sameer S Levin Albert M AM Shetty Aniket A Gignoux Christopher R CR Boorgula Meher Preethi MP Wojcik Genevieve G Campbell Monica M Vergara Candelaria C Torgerson Dara G DG Ortega Victor E VE Doumatey Ayo A Johnston Henry Richard HR Acevedo Nathalie N Araujo Maria Ilma MI Avila Pedro C PC Belbin Gillian G Bleecker Eugene E Bustamante Carlos C Caraballo Luis L Cruz Alvaro A Dunston Georgia M GM Eng Celeste C Faruque Mezbah U MU Ferguson Trevor S TS Figueiredo Camila C Ford Jean G JG Gan Weiniu W Gourraud Pierre-Antoine PA Hansel Nadia N NN Hernandez Ryan D RD Herrera-Paz Edwin Francisco EF Jiménez Silvia S Kenny Eimear E EE Knight-Madden Jennifer J Kumar Rajesh R Lange Leslie A LA Lange Ethan M EM Lizee Antoine A Maul Pissamai P Maul Trevor T Mayorga Alvaro A Meyers Deborah D Nicolae Dan L DL O'Connor Timothy D TD Oliveira Ricardo Riccio RR Olopade Christopher O CO Olopade Olufunmilayo O Qin Zhaohui S ZS Rotimi Charles C Vince Nicolas N Watson Harold H Wilks Rainford J RJ Wilson James G JG Salzberg Steven S Ober Carole C Burchard Esteban G EG Williams L Keoki LK Beaty Terri H TH Taub Margaret A MA Ruczinski Ingo I Mathias Rasika A RA Barnes Kathleen C KC

Nature communications 20190220 1

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find ...[more]

PMID: 30787307

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Project description:Admixed populations arise when two or more previously isolated populations interbreed. Mapping asthma susceptibility loci in an admixed population using admixture mapping (AM) involves screening the genome of individuals of mixed ancestry for chromosomal regions that have a higher frequency of alleles from a parental population with higher asthma risk as compared with parental population with lower asthma risk. AM takes advantage of the admixture created in populations of mixed ancestry to identify genomic regions where an association exists between genetic ancestry and asthma (in contrast to between the genotype of the marker and asthma). The theory behind AM is that chromosomal segments of affected individuals contain a significantly higher-than-average proportion of alleles from the high-risk parental population and thus are more likely to harbor disease-associated loci. Criteria to evaluate the applicability of AM as a gene mapping approach include: (1) the prevalence of the disease differences in ancestral populations from which the admixed population was formed; (2) a measurable difference in disease-causing alleles between the parental populations; (3) reduced linkage disequilibrium (LD) between unlinked loci across chromosomes and strong LD between neighboring loci; (4) a set of markers with noticeable allele-frequency differences between parental populations that contributes to the admixed population (single nucleotide polymorphisms (SNPs) are the markers of choice because they are abundant, stable, relatively cheap to genotype, and informative with regard to the LD structure of chromosomal segments); and (5) there is an understanding of the extent of segmental chromosomal admixtures and their interactions with environmental factors. Although genome-wide association studies have contributed greatly to our understanding of the genetic components of asthma, the large and increasing degree of admixture in populations across the world create many challenges for further efforts to map disease-causing genes. This review, summarizes the historical context of admixed populations and AM, and considers current opportunities to use AM to map asthma genes. In addition, we provide an overview of the potential limitations and future directions of AM in biomedical research, including joint admixture and association mapping for asthma and asthma-related disorders.

Dataset Information

Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Publications

Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

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