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

Daya, Michelle; Rafaels, Nicholas; Brunetti, Tonya M.; Chavan, Sameer; Levin, Albert M.; Shetty, Aniket; Gignoux, Christopher R.; Boorgula, Meher Preethi; Wojcik, Genevieve L.; Campbell, Monica; Vergara, Candelaria; Torgerson, Dara G.; Ortega, Victor E.; Doumatey, Ayo P.; Johnston, H. Richard; Acevedo, Nathalie; Araújo, Maria Ilma; Avila, Pedro C.; Belbin, Gillian M.; Bleecker, Eugene R.; Bustamante, Carlos D.; Caraballo, Luis; Cruz, Ãlvaro A.; Dunston, Georgia M.; Eng, Celeste; Faruque, Mezbah U.; Ferguson, Trevor S.; Figueiredo, Camila A.; Ford, Jean G.; Gan, Weiniu; Gourraud, Pierre‐Antoine; Hansel, Nadia N.; Hernández, Ryan D.; Herrera-Paz, Edwin Francisco; Jiménez, Silvia; Kenny, Eimear E.; Knight‐Madden, Jennifer; Kumar, Rajesh; Lange, Leslie A.; Lange, Ethan M.; Lizée, Antoine; Maul, Pissamai; Maul, Trevor; Mayorga, Alvaro; Meyers, Deborah A.; Nicolae, Dan L.; O’Connor, Timothy D.; Oliveira, Ricardo Riccio; Olopade, Christopher O.; Olopade, Olufunmilayo I.; Qin, Zhaohui S.; Rotimi, Charles N.; Vince, Nicolas; Watson, Harold; Wilks, Rainford; Wilson, James G.; Salzberg, Steven L.; Ober, Carole; Burchard, Esteban G.; Williams, L. Keoki; Beaty, Terri H.; Taub, Margaret A.; Ruczinski, Ingo; Mathias, Rasika A.; Barnes, Kathleen C.; Caapa,

doi:10.1038/s41467-019-08469-7

Cited by 80 publications

(43 citation statements)

References 69 publications

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“…We had access to the CAAPA (Consortium on Asthma among African-ancestry Populations in the Americas) data set (Daya et al, 2019;Vince et al, 2020) that consists of 880 whole-genome sequenced African American subjects with associated SNP GWAS data and typed HLA alleles at a two-field resolution (corresponding to the protein level). We chose the HLA Genotype Imputation with Attribute Bagging (HIBAG) R package (Zheng et al, 2014) to test the impact of the number of subjects and SNPs on HLA imputation accuracy.…”

Section: Resultsmentioning

confidence: 99%

SNP‐HLA Reference Consortium (SHLARC): HLA and SNP data sharing for promoting MHC‐centric analyses in genomics

Vince

Douillard

Geffard

et al. 2020

Genetic Epidemiology

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Genome‐wide associations studies have repeatedly identified the major histocompatibility complex genomic region (6p21.3) as key in immune pathologies. Researchers have also aimed to extend the biological interpretation of associations by focusing directly on human leukocyte antigen (HLA) polymorphisms and their combination as haplotypes. To circumvent the effort and high costs of HLA typing, statistical solutions have been developed to infer HLA alleles from single‐nucleotide polymorphism (SNP) genotyping data. Though HLA imputation methods have been developed, no unified effort has yet been undertaken to share large and diverse imputation models, or to improve methods. By training the HIBAG software on SNP + HLA data generated by the Consortium on Asthma among African‐ancestry Populations in the Americas (CAAPA) to create reference panels, we highlighted the importance of (a) the number of individuals in reference panels, with a twofold increase in accuracy (from 10 to 100 individuals) and (b) the number of SNPs, with a 1.5‐fold increase in accuracy (from 500 to 24,504 SNPs). Results showed improved accuracy with CAAPA compared to the African American models available in HIBAG, highlighting the need for precise population‐matching. The SNP‐HLA Reference Consortium is an international endeavor to gather data, enhance HLA imputation and broaden access to highly accurate imputation models for the immunogenomics community.

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Section: Resultsmentioning

confidence: 99%

SNP‐HLA Reference Consortium (SHLARC): HLA and SNP data sharing for promoting MHC‐centric analyses in genomics

Vince

Douillard

Geffard

et al. 2020

Genetic Epidemiology

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“…We obtained genome-wide summary statistics for HbA1c, 15 asthma, 16 , 17 and prostate cancer 18 , 19 calculated in European and African ancestry individuals ( Table S1 ). Summary statistic variants that were not present in both the UK Biobank European and African ancestry testing populations were removed.…”

Section: Methodsmentioning

confidence: 99%

Inclusion of variants discovered from diverse populations improves polygenic risk score transferability

Cavazos

Witte

2021

Human Genetics and Genomics Advances

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Summary The majority of polygenic risk scores (PRSs) have been developed and optimized in individuals of European ancestry and may have limited generalizability across other ancestral populations. Understanding aspects of PRSs that contribute to this issue and determining solutions is complicated by disease-specific genetic architecture and limited knowledge of sharing of causal variants and effect sizes across populations. Motivated by these challenges, we undertook a simulation study to assess the relationship between ancestry and the potential bias in PRSs developed in European ancestry populations. Our simulations show that the magnitude of this bias increases with increasing divergence from European ancestry, and this is attributed to population differences in linkage disequilibrium and allele frequencies of European-discovered variants, likely as a result of genetic drift. Importantly, we find that including into the PRS variants discovered in African ancestry individuals has the potential to achieve unbiased estimates of genetic risk across global populations and admixed individuals. We confirm our simulation findings in an analysis of hemoglobin A1c (HbA1c), asthma, and prostate cancer in the UK Biobank. Given the demonstrated improvement in PRS prediction accuracy, recruiting larger diverse cohorts will be crucial—and potentially even necessary—for enabling accurate and equitable genetic risk prediction across populations.

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“…The more links a gene has, the more general the role of its mutations in allergic mechanisms may be and imputation tools for that ancestry were not available. Only in 2019, the first large-scale GWAS on asthma in African Americans was published by the Consortium on Asthma among populations of African Ancestry in the Americas (CAAPA) [22]. In a landmark effort, the consortium first sequenced almost 900 individuals of African ancestry to create an imputation base.…”

Section: Asthma and Allergy Genetics In Non-caucasian Populationsmentioning

confidence: 99%

Recent findings in the genetics and epigenetics of asthma and allergy

Kabesch¹,

Tost

2020

Semin Immunopathol

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In asthma and allergy genetics, a trend towards a few main topics developed over the last 2 years. First, a number of studies have been published recently which focus on overlapping and/or very specific phenotypes: within the allergy spectrum but also reaching beyond, looking for common genetic traits shared between different diseases or disease entities. Secondly, an urgently needed focus has been put on asthma and allergy genetics in populations genetically different from European ancestry. This acknowledges that the majority of new asthma patients today are not white and asthma is a truly worldwide disease. In epigenetics, recent years have seen several large-scale epigenome-wide association studies (EWAS) being published and a further focus was on the interaction between the environment and epigenetic signatures. And finally, the major trends in current asthma and allergy genetics and epigenetics comes from the field of pharmacogenetics, where it is necessary to understand the susceptibility for and mechanisms of current asthma and allergy therapies while at the same time, we need to have scientific answers to the recent availability of novel drugs that hold the promise for a more individualized therapy.

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

Cited by 80 publications

References 69 publications

SNP‐HLA Reference Consortium (SHLARC): HLA and SNP data sharing for promoting MHC‐centric analyses in genomics

SNP‐HLA Reference Consortium (SHLARC): HLA and SNP data sharing for promoting MHC‐centric analyses in genomics

Inclusion of variants discovered from diverse populations improves polygenic risk score transferability

Recent findings in the genetics and epigenetics of asthma and allergy

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