Admixture mapping identifies African and Amerindigenous local ancestry loci associated with fetal growth

The prevalence of asthma symptoms in Canary Islanders, a southwestern European population from Spain, is almost three times higher than the country average. Because the genetic risks identified so far explain <5% of asthma heritability, here we aimed to discover new asthma loci by completing the first admixture mapping study in Canary Islanders leveraging their distinctive genetic makeup, where significant northwest African influences coexist in the European genetic diversity landscape. A 2-stage study was conducted in 1,491 unrelated individuals self-declaring having a Canary Islands origin for the 4 grandparents. Local ancestry estimates were obtained for the shared positions with reference data from putative ancestral populations from Europe, North Africa, and sub-Saharan Africa. Case-control deviations in local ancestry were tested for each ancestry separately using logistic regressions adjusted for principal components, followed by fine-mapping analyses based on imputed genotypes and analyses of the likely deleterious exonic variants. The admixture mapping analysis of asthma detected that local North African ancestry in a locus spanning 365 kb of chromosome 16q23.3 was associated with asthma risk at study-wide significance [lowest P = 1.12 × 10−4; odds ratio (OR) = 2.05; 95% confidence interval (CI) = 1.41–3.00]. Fine-mapping studies identified a variant associated with asthma, and results were replicated in independent samples (rs3852738, OR = 1.34; 95% CI = 1.13–1.59, P = 7.58 × 10−4). Whole exome sequencing data from a subset of individuals revealed an enrichment of likely deleterious variants among asthma cases in 16q23.3, particularly in the phospholipase Cγ2 ( PLCG2) gene ( P = 3.67 × 10−4). By completing the first mapping study of asthma in admixed populations from Europe, our results revealed a new plausible asthma locus.

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Deconvoluting complex correlates of COVID19 severity with local ancestry inference and viral phylodynamics: Results of a multiomic pandemic tracking strategy

10.1101/2021.08.04.21261547 ◽

2021 ◽

Author(s):

V N Parikh ◽

A G Ioannidis ◽

D Jimenez-Morales ◽

J E Gorzynski ◽

H N De Jong ◽

...

Keyword(s):

Human Leukocyte ◽

Hla Typing ◽

Admixture Mapping ◽

Nasopharyngeal Swab ◽

Social Constructs ◽

Viral Genomes ◽

Local Ancestry ◽

Ancestry Inference ◽

Local Ancestry Inference ◽

Tracking Strategy

The SARS-CoV-2 pandemic has differentially impacted populations of varied race, ethnicity and socioeconomic status. Admixture mapping and local ancestry inference represent powerful tools to examine genetic risk within multi-ancestry genomes independent of these confounding social constructs. Here, we leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from 1,327 nasopharyngeal swab residuals and integrate them with digital phenotypes from electronic health records. We demonstrate over-representation of individuals possessing Oceanian and Indigenous American ancestry in SARS-CoV-2 positive populations. Genome-wide-association disaggregated by admixture mapping reveals regions of chromosomes 5 and 14 associated with COVID19 severity within African and Oceanic local ancestries, respectively, independent of overall ancestry fraction. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. We further present summary data from a multi-omic investigation of human-leukocyte-antigen (HLA) typing, nasopharyngeal microbiome and human transcriptomics that reveal metagenomic and HLA associations with severe COVID19 infection. This work demonstrates the power of multi-omic pandemic tracking and genomic analyses to reveal distinct epidemiologic, genetic and biological associations for those at the highest risk.

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Mixed-model admixture mapping identifies smoking-dependent loci of lung function in African Americans

10.1101/626077 ◽

2019 ◽

Author(s):

Andrey Ziyatdinov ◽

Margaret M. Parker ◽

Amaury Vaysse ◽

Terri H. Beaty ◽

Peter Kraft ◽

...

Keyword(s):

African Americans ◽

Lung Function ◽

Mixed Model ◽

Disease Risk ◽

Association Studies ◽

Admixture Mapping ◽

Local Ancestry ◽

Genome Wide ◽

Genes And Environment ◽

A Genome

AbstractAdmixture mapping has led to the discovery of many genes associated with differential disease risk by ancestry, highlighting the importance of ancestry-based approaches to association studies. However, the potential of admixture mapping in deciphering the interplay between genes and environment exposures has been seldom explored. Here, we performed a genome-wide screening of local ancestry-smoking interactions for five spirometric lung function phenotypes in 3,300 African Americans from the COPDGene study. To account for population structure and outcome heterogeneity across exposure groups, we developed a multi-component linear mixed model for mapping gene-environment interactions, and empirically showed its robustness and increased power. When applied to the COPDGene study, our approach identified two 11p15.2-3 and 2q37 loci, exhibiting local ancestry-smoking interactions at genome-wide significant level, that would have been missed by standard singlenucleotide polymorphism analyses. These two loci harbor the PARVA and RAB17 genes previously recognized to be involved in smoking behavior. Overall, our study provides the first evidence for potential synergistic effects between African ancestry and smoking on pulmonary function and underlines the importance of ethnic diversity in genetic studies.

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