Research output: Contribution to journal › Article › peer-review
Nontrivial Replication of Loci Detected by Multi-Trait Methods. / Ning, Zheng; Tsepilov, Yakov A.; Sharapov, Sodbo Zh et al.
In: Frontiers in Genetics, Vol. 12, 627989, 03.02.2021.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Nontrivial Replication of Loci Detected by Multi-Trait Methods
AU - Ning, Zheng
AU - Tsepilov, Yakov A.
AU - Sharapov, Sodbo Zh
AU - Wang, Zhipeng
AU - Grishenko, Alexander K.
AU - Feng, Xiao
AU - Shirali, Masoud
AU - Joshi, Peter K.
AU - Wilson, James F.
AU - Pawitan, Yudi
AU - Haley, Chris S.
AU - Aulchenko, Yurii S.
AU - Shen, Xia
N1 - Publisher Copyright: © Copyright © 2021 Ning, Tsepilov, Sharapov, Wang, Grishenko, Feng, Shirali, Joshi, Wilson, Pawitan, Haley, Aulchenko and Shen.
PY - 2021/2/3
Y1 - 2021/2/3
N2 - 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.
AB - 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.
KW - cross-phenotype association
KW - genome-wide association study
KW - genotype-phenotype map
KW - multivariate analysis
KW - pleiotropy
KW - replication
UR - http://www.scopus.com/inward/record.url?scp=85101177734&partnerID=8YFLogxK
U2 - 10.3389/fgene.2021.627989
DO - 10.3389/fgene.2021.627989
M3 - Article
C2 - 33613642
AN - SCOPUS:85101177734
VL - 12
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
M1 - 627989
ER -
ID: 27966753