Trans-ethnic study design approaches for fine-mapping

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 becaus...

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Main Authors:	Asimit, Jennifer L, Hatzikotoulas, Konstantinos, McCarthy, Mark, Morris, Andrew P, Zeggini, Eleftheria
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856879/

id	pubmed-4856879
recordtype	oai_dc
spelling	pubmed-48568792016-08-30 Trans-ethnic study design approaches for fine-mapping Asimit, Jennifer L Hatzikotoulas, Konstantinos McCarthy, Mark Morris, Andrew P Zeggini, Eleftheria Article 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. Nature Publishing Group 2016-08 2016-02-03 /pmc/articles/PMC4856879/ /pubmed/26839038 http://dx.doi.org/10.1038/ejhg.2016.1 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Asimit, Jennifer L Hatzikotoulas, Konstantinos McCarthy, Mark Morris, Andrew P Zeggini, Eleftheria
spellingShingle	Asimit, Jennifer L Hatzikotoulas, Konstantinos McCarthy, Mark Morris, Andrew P Zeggini, Eleftheria Trans-ethnic study design approaches for fine-mapping
author_facet	Asimit, Jennifer L Hatzikotoulas, Konstantinos McCarthy, Mark Morris, Andrew P Zeggini, Eleftheria
author_sort	Asimit, Jennifer L
title	Trans-ethnic study design approaches for fine-mapping
title_short	Trans-ethnic study design approaches for fine-mapping
title_full	Trans-ethnic study design approaches for fine-mapping
title_fullStr	Trans-ethnic study design approaches for fine-mapping
title_full_unstemmed	Trans-ethnic study design approaches for fine-mapping
title_sort	trans-ethnic study design approaches for fine-mapping
description	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.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856879/
_version_	1613575477723660288

Trans-ethnic study design approaches for fine-mapping

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