AUTHOR=Ning Zheng , Tsepilov Yakov A. , Sharapov Sodbo Zh. , Wang Zhipeng , Grishenko Alexander K. , Feng Xiao , Shirali Masoud , Joshi Peter K. , Wilson James F. , Pawitan Yudi , Haley Chris S. , Aulchenko Yurii S. , Shen Xia TITLE=Nontrivial Replication of Loci Detected by Multi-Trait Methods JOURNAL=Frontiers in Genetics VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.627989 DOI=10.3389/fgene.2021.627989 ISSN=1664-8021 ABSTRACT=

The ever-growing genome-wide association studies (GWAS) have revealed widespread pleiotropy. To exploit this, various methods that jointly consider associations of a genetic variant with multiple traits have been developed. Most efforts have been made concerning improving GWAS discovery power. However, how to replicate these discovered pleiotropic loci has yet to be discussed thoroughly. Unlike a single-trait scenario, multi-trait replication is not trivial considering the underlying genotype-multi-phenotype map of the associations. Here, we evaluate four methods for replicating multi-trait associations, corresponding to four levels of replication strength. Weak replication cannot justify pleiotropic genetic effects, whereas strong replication using our developed correlation methods can inform consistent pleiotropic genetic effects across the discovery and replication samples. We provide a protocol for replicating multi-trait genetic associations in practice. The described methods are implemented in the free and open-source R package MultiABEL.