Trans-ethnic study design approaches for fine-mapping



Asimit, Jennifer L, Hatzikotoulas, Konstantinos, McCarthy, Mark, Morris, Andrew P and Zeggini, Eleftheria
(2016) Trans-ethnic study design approaches for fine-mapping. EUROPEAN JOURNAL OF HUMAN GENETICS, 24 (9). pp. 1330-1336.

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Abstract

Studies that traverse ancestrally diverse populations may increase power to detect novel loci and improve fine-mapping resolution of causal variants by leveraging linkage disequilibrium differences between ethnic groups. The inclusion of African ancestry samples may yield further improvements because of low linkage disequilibrium and high genetic heterogeneity. We investigate the fine-mapping resolution of trans-ethnic fixed-effects meta-analysis for five type II diabetes loci, under various settings of ancestral composition (European, East Asian, African), allelic heterogeneity, and causal variant minor allele frequency. In particular, three settings of ancestral composition were compared: (1) single ancestry (European), (2) moderate ancestral diversity (European and East Asian), and (3) high ancestral diversity (European, East Asian, and African). Our simulations suggest that the European/Asian and European ancestry-only meta-analyses consistently attain similar fine-mapping resolution. The inclusion of African ancestry samples in the meta-analysis leads to a marked improvement in fine-mapping resolution.

Item Type: Article
Uncontrolled Keywords: Humans, Diabetes Mellitus, Type 2, Chromosome Mapping, Pedigree, Linkage Disequilibrium, Genetic Heterogeneity, Polymorphism, Single Nucleotide, Algorithms, Models, Genetic, Research Design, Meta-Analysis as Topic, Genome-Wide Association Study, Genetic Loci, Racial Groups
Depositing User: Symplectic Admin
Date Deposited: 22 Jun 2016 08:50
Last Modified: 19 Jan 2023 07:35
DOI: 10.1038/ejhg.2016.1
Open Access URL: http://www.nature.com/ejhg/journal/vaop/ncurrent/f...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3001806