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Implications of population structure and ancestry on asthma genetic studies.

ABSTRACT: The frequency and severity of asthma differ between different racial and ethnic groups. An understanding of the genetic basis for these differences could constitute future genetic biomarker panels for predicting asthma risk and progression in individuals from different ethnic groups.The recent mixing of different ancestries during the European colonization of the Americas and the African slave trade has resulted in the complex population structures identified in different ethnic groups. These population structures represent varying degrees of genetic diversity which impacts the allele frequency of individual variants and, thus, how the gene variation is utilized in genetic association studies. In this review, we will discuss the basis for the complex population structures of modern human genomes and the impact of genetic diversity on genetic studies in different ethnic groups. We will also highlight the potential for admixture and rare variant-based genetic studies to identify novel genetic loci for asthma susceptibility and severity.The ability to account for the consequences of genetic diversity in different racial and ethnic groups will be critical in developing genetic profiles for personalized or precision medicine approaches tailored to asthmatic patients from different ethnic groups.

SUBMITTER: Ortega VE

PROVIDER: S-EPMC4278361 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Implications of population structure and ancestry on asthma genetic studies.

Ortega Victor E VE Meyers Deborah A DA

Current opinion in allergy and clinical immunology 20141001 5

<h4>Purpose of review</h4>The frequency and severity of asthma differ between different racial and ethnic groups. An understanding of the genetic basis for these differences could constitute future genetic biomarker panels for predicting asthma risk and progression in individuals from different ethnic groups.<h4>Recent themes</h4>The recent mixing of different ancestries during the European colonization of the Americas and the African slave trade has resulted in the complex population structures ...[more]

PMID: 25153337

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Project description:The Caribbean is a genetically diverse region with heterogeneous admixture compositions influenced by local island ecologies, migrations, colonial conflicts, and demographic histories. The Commonwealth of Dominica is a mountainous island in the Lesser Antilles historically known to harbor communities with unique patterns of migration, mixture, and isolation. This community-based population genetic study adds biological evidence to inform post-colonial narrative histories in a Dominican horticultural village. High density single nucleotide polymorphism data paired with a previously compiled genealogy provide the first genome-wide insights on genetic ancestry and population structure in Dominica. We assessed family-based clustering, inferred global ancestry, and dated recent admixture by implementing the fastSTRUCTURE clustering algorithm, modeling graph-based migration with TreeMix, assessing patterns of linkage disequilibrium decay with ALDER, and visualizing data from Dominica with Human Genome Diversity Panel references. These analyses distinguish family-based genetic structure from variation in African, European, and indigenous Amerindian admixture proportions, and analyses of linkage disequilibrium decay estimate admixture dates 5-6 generations (~160 years) ago. African ancestry accounts for the largest mixture components, followed by European and then indigenous components; however, our global ancestry inferences are consistent with previous mitochondrial, Y chromosome, and ancestry marker data from Dominica that show uniquely higher proportions of indigenous ancestry and lower proportions of African ancestry relative to known admixture in other French- and English-speaking Caribbean islands. Our genetic results support local narratives about the community's history and founding, which indicate that newly emancipated people settled in the steep, dense vegetation along Dominica's eastern coast in the mid-19th century. Strong genetic signals of post-colonial admixture and family-based structure highlight the localized impacts of colonial forces and island ecologies in this region, and more data from other groups are needed to more broadly inform on Dominica's complex history and present diversity.

Dataset Information

Implications of population structure and ancestry on asthma genetic studies.

Publications

Implications of population structure and ancestry on asthma genetic studies.

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