作者
Ran Cui, Roy A Elzur, Masahiro Kanai, Jacob C Ulirsch, Omer Weissbrod, Mark J Daly, Benjamin M Neale, Zhou Fan, Hilary K Finucane
发表日期
2024/1
期刊
Nature genetics
卷号
56
期号
1
页码范围
162-169
出版商
Nature Publishing Group US
简介
Fine-mapping aims to identify causal genetic variants for phenotypes. Bayesian fine-mapping algorithms (for example, SuSiE, FINEMAP, ABF and COJO-ABF) are widely used, but assessing posterior probability calibration remains challenging in real data, where model misspecification probably exists, and true causal variants are unknown. We introduce replication failure rate (RFR), a metric to assess fine-mapping consistency by downsampling. SuSiE, FINEMAP and COJO-ABF show high RFR, indicating potential overconfidence in their output. Simulations reveal that nonsparse genetic architecture can lead to miscalibration, while imputation noise, nonuniform distribution of causal variants and quality control filters have minimal impact. Here we present SuSiE-inf and FINEMAP-inf, fine-mapping methods modeling infinitesimal effects alongside fewer larger causal effects. Our methods show improved calibration …
引用总数
学术搜索中的文章
R Cui, RA Elzur, M Kanai, JC Ulirsch, O Weissbrod… - Nature genetics, 2024