Trans-ethnic study design approaches for fine-mapping.


Type
Article
Change log
Authors
Asimit, Jennifer L 
Hatzikotoulas, Konstantinos 
McCarthy, Mark 
Morris, Andrew P 
Zeggini, Eleftheria  ORCID logo  https://orcid.org/0000-0003-4238-659X
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.

Description
Keywords
Algorithms, Chromosome Mapping, Diabetes Mellitus, Type 2, Genetic Heterogeneity, Genetic Loci, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Meta-Analysis as Topic, Models, Genetic, Pedigree, Polymorphism, Single Nucleotide, Racial Groups, Research Design
Journal Title
Eur J Hum Genet
Conference Name
Journal ISSN
1018-4813
1476-5438
Volume Title
24
Publisher
Springer Science and Business Media LLC