How Well Can Multivariate and Univariate GWAS Distinguish Between True and Spurious Pleiotropy?
Quantification of the simultaneous contributions of loci to multiple traits, a phenomenon called pleiotropy, is facilitated by the increased availability of high-throughput genotypic and phenotypic data. To understand the prevalence and nature of pleiotropy, the ability of multivariate and univariat...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-01-01
|
Series: | Frontiers in Genetics |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.602526/full |
id |
doaj-ab919b9697b44eb5b31cf8bc5c4dce00 |
---|---|
record_format |
Article |
spelling |
doaj-ab919b9697b44eb5b31cf8bc5c4dce002021-01-08T06:52:14ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-01-011110.3389/fgene.2020.602526602526How Well Can Multivariate and Univariate GWAS Distinguish Between True and Spurious Pleiotropy?Samuel B. FernandesKevin S. ZhangTiffany M. JamannAlexander E. LipkaQuantification of the simultaneous contributions of loci to multiple traits, a phenomenon called pleiotropy, is facilitated by the increased availability of high-throughput genotypic and phenotypic data. To understand the prevalence and nature of pleiotropy, the ability of multivariate and univariate genome-wide association study (GWAS) models to distinguish between pleiotropic and non-pleiotropic loci in linkage disequilibrium (LD) first needs to be evaluated. Therefore, we used publicly available maize and soybean genotypic data to simulate multiple pairs of traits that were either (i) controlled by quantitative trait nucleotides (QTNs) on separate chromosomes, (ii) controlled by QTNs in various degrees of LD with each other, or (iii) controlled by a single pleiotropic QTN. We showed that multivariate GWAS could not distinguish between QTNs in LD and a single pleiotropic QTN. In contrast, a unique QTN detection rate pattern was observed for univariate GWAS whenever the simulated QTNs were in high LD or pleiotropic. Collectively, these results suggest that multivariate and univariate GWAS should both be used to infer whether or not causal mutations underlying peak GWAS associations are pleiotropic. Therefore, we recommend that future studies use a combination of multivariate and univariate GWAS models, as both models could be useful for identifying and narrowing down candidate loci with potential pleiotropic effects for downstream biological experiments.https://www.frontiersin.org/articles/10.3389/fgene.2020.602526/fullSimulationmulti-traitUnified Mixed-ModelQTNmaizesoybean |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Samuel B. Fernandes Kevin S. Zhang Tiffany M. Jamann Alexander E. Lipka |
spellingShingle |
Samuel B. Fernandes Kevin S. Zhang Tiffany M. Jamann Alexander E. Lipka How Well Can Multivariate and Univariate GWAS Distinguish Between True and Spurious Pleiotropy? Frontiers in Genetics Simulation multi-trait Unified Mixed-Model QTN maize soybean |
author_facet |
Samuel B. Fernandes Kevin S. Zhang Tiffany M. Jamann Alexander E. Lipka |
author_sort |
Samuel B. Fernandes |
title |
How Well Can Multivariate and Univariate GWAS Distinguish Between True and Spurious Pleiotropy? |
title_short |
How Well Can Multivariate and Univariate GWAS Distinguish Between True and Spurious Pleiotropy? |
title_full |
How Well Can Multivariate and Univariate GWAS Distinguish Between True and Spurious Pleiotropy? |
title_fullStr |
How Well Can Multivariate and Univariate GWAS Distinguish Between True and Spurious Pleiotropy? |
title_full_unstemmed |
How Well Can Multivariate and Univariate GWAS Distinguish Between True and Spurious Pleiotropy? |
title_sort |
how well can multivariate and univariate gwas distinguish between true and spurious pleiotropy? |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2021-01-01 |
description |
Quantification of the simultaneous contributions of loci to multiple traits, a phenomenon called pleiotropy, is facilitated by the increased availability of high-throughput genotypic and phenotypic data. To understand the prevalence and nature of pleiotropy, the ability of multivariate and univariate genome-wide association study (GWAS) models to distinguish between pleiotropic and non-pleiotropic loci in linkage disequilibrium (LD) first needs to be evaluated. Therefore, we used publicly available maize and soybean genotypic data to simulate multiple pairs of traits that were either (i) controlled by quantitative trait nucleotides (QTNs) on separate chromosomes, (ii) controlled by QTNs in various degrees of LD with each other, or (iii) controlled by a single pleiotropic QTN. We showed that multivariate GWAS could not distinguish between QTNs in LD and a single pleiotropic QTN. In contrast, a unique QTN detection rate pattern was observed for univariate GWAS whenever the simulated QTNs were in high LD or pleiotropic. Collectively, these results suggest that multivariate and univariate GWAS should both be used to infer whether or not causal mutations underlying peak GWAS associations are pleiotropic. Therefore, we recommend that future studies use a combination of multivariate and univariate GWAS models, as both models could be useful for identifying and narrowing down candidate loci with potential pleiotropic effects for downstream biological experiments. |
topic |
Simulation multi-trait Unified Mixed-Model QTN maize soybean |
url |
https://www.frontiersin.org/articles/10.3389/fgene.2020.602526/full |
work_keys_str_mv |
AT samuelbfernandes howwellcanmultivariateandunivariategwasdistinguishbetweentrueandspuriouspleiotropy AT kevinszhang howwellcanmultivariateandunivariategwasdistinguishbetweentrueandspuriouspleiotropy AT tiffanymjamann howwellcanmultivariateandunivariategwasdistinguishbetweentrueandspuriouspleiotropy AT alexanderelipka howwellcanmultivariateandunivariategwasdistinguishbetweentrueandspuriouspleiotropy |
_version_ |
1724344682392059904 |