Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex human traits, but only a fraction of variants identified in discovery studies achieve significance in replication studies. Replication in genome-wide association studies has been well-studied in the context of Winner’s Curse, which is the inflation of effect size estimates for significant variants due to statistical chance. However, Winner’s Curse is often not sufficient to explain lack of replication. Another reason why studies fail to replicate is that there are fundamental differences between the discovery and replication studies. A confounding factor can create the appearance of a significant finding while actually being an artifact that will not replicate in future studies. We propose a statistical framework that utilizes genome-wide association studies and replication studies to jointly model Winner’s Curse and study-specific heterogeneity due to confounding factors. We apply this framework to 100 genome-wide association studies from the Human Genome-Wide Association Studies Catalog and observe that there is a large range in the level of estimated confounding. We demonstrate how this framework can be used to distinguish when studies fail to replicate due to statistical noise and when they fail due to confounding.
- Award ID(s):
- 1910885
- NSF-PAR ID:
- 10348476
- Editor(s):
- Matise, T
- Date Published:
- Journal Name:
- G3 Genes|Genomes|Genetics
- Volume:
- 12
- Issue:
- 1
- ISSN:
- 2160-1836
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Background Genome wide association (GWA) studies demonstrate linkages between genetic variants and traits of interest. Here, we tested associations between single nucleotide polymorphisms (SNPs) in rice (
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Arabidopsis .Conclusions Root hair length and density are quantitative traits with complex and independent genetic control in rice. The genomic regions described here could be used as the basis for QTL development and further analysis of the genetic control of root hair length and density. We present a list of candidate genes involved in root hair formation and growth in rice, many of which have not been previously identified as having a relation to root hair growth. Since little is known about root hair growth in grasses, these provide a guide for further research and crop improvement.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/g3journal/jkab394
