Leveraging information between multiple population groups and traits improves fine-mapping resolution

Autor: Feng Zhou, Opeyemi Soremekun, Tinashe Chikowore, Segun Fatumo, Inês Barroso, Andrew P. Morris, Jennifer L. Asimit
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nature Communications, Vol 14, Iss 1, Pp 1-12 (2023)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-023-43159-5
Popis: Abstract Statistical fine-mapping helps to pinpoint likely causal variants underlying genetic association signals. Its resolution can be improved by (i) leveraging information between traits; and (ii) exploiting differences in linkage disequilibrium structure between diverse population groups. Using association summary statistics, MGflashfm jointly fine-maps signals from multiple traits and population groups; MGfm uses an analogous framework to analyse each trait separately. We also provide a practical approach to fine-mapping with out-of-sample reference panels. In simulation studies we show that MGflashfm and MGfm are well-calibrated and that the mean proportion of causal variants with PP > 0.80 is above 0.75 (MGflashfm) and 0.70 (MGfm). In our analysis of four lipids traits across five population groups, MGflashfm gives a median 99% credible set reduction of 10.5% over MGfm. MGflashfm and MGfm only require summary level data, making them very useful fine-mapping tools in consortia efforts where individual-level data cannot be shared.
Databáze: Directory of Open Access Journals