Is replication the gold standard for validating genome-wide association findings?
With the advent of genome-wide association (GWA) studies, researchers are hoping that reliable genetic association of common human complex diseases/traits can be detected. Currently, there is an increasing enthusiasm about GWA and a number of GWA studies have been published. In the field a common pr...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2605260?pdf=render |
| _version_ | 1819138765925384192 |
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| author | Yong-Jun Liu Christopher J Papasian Jian-Feng Liu James Hamilton Hong-Wen Deng |
| author_facet | Yong-Jun Liu Christopher J Papasian Jian-Feng Liu James Hamilton Hong-Wen Deng |
| author_sort | Yong-Jun Liu |
| collection | DOAJ |
| description | With the advent of genome-wide association (GWA) studies, researchers are hoping that reliable genetic association of common human complex diseases/traits can be detected. Currently, there is an increasing enthusiasm about GWA and a number of GWA studies have been published. In the field a common practice is that replication should be used as the gold standard to validate an association finding. In this article, based on empirical and theoretical data, we emphasize that replication of GWA findings can be quite difficult, and should not always be expected, even when true variants are identified. The probability of replication becomes smaller with the increasing number of independent GWA studies if the power of individual replication studies is less than 100% (which is usually the case), and even a finding that is replicated may not necessarily be true. We argue that the field may have unreasonably high expectations on success of replication. We also wish to raise the question whether it is sufficient or necessary to treat replication as the ultimate and gold standard for defining true variants. We finally discuss the usefulness of integrating evidence from multiple levels/sources such as genetic epidemiological studies (at the DNA level), gene expression studies (at the RNA level), proteomics (at the protein level), and follow-up molecular and cellular studies for eventual validation and illumination of the functional relevance of the genes uncovered. |
| first_indexed | 2024-12-22T11:11:59Z |
| format | Article |
| id | doaj.art-870d0e6dfdbf495eb81ade7fec584995 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T11:11:59Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-870d0e6dfdbf495eb81ade7fec5849952022-12-21T18:28:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01312e403710.1371/journal.pone.0004037Is replication the gold standard for validating genome-wide association findings?Yong-Jun LiuChristopher J PapasianJian-Feng LiuJames HamiltonHong-Wen DengWith the advent of genome-wide association (GWA) studies, researchers are hoping that reliable genetic association of common human complex diseases/traits can be detected. Currently, there is an increasing enthusiasm about GWA and a number of GWA studies have been published. In the field a common practice is that replication should be used as the gold standard to validate an association finding. In this article, based on empirical and theoretical data, we emphasize that replication of GWA findings can be quite difficult, and should not always be expected, even when true variants are identified. The probability of replication becomes smaller with the increasing number of independent GWA studies if the power of individual replication studies is less than 100% (which is usually the case), and even a finding that is replicated may not necessarily be true. We argue that the field may have unreasonably high expectations on success of replication. We also wish to raise the question whether it is sufficient or necessary to treat replication as the ultimate and gold standard for defining true variants. We finally discuss the usefulness of integrating evidence from multiple levels/sources such as genetic epidemiological studies (at the DNA level), gene expression studies (at the RNA level), proteomics (at the protein level), and follow-up molecular and cellular studies for eventual validation and illumination of the functional relevance of the genes uncovered.http://europepmc.org/articles/PMC2605260?pdf=render |
| spellingShingle | Yong-Jun Liu Christopher J Papasian Jian-Feng Liu James Hamilton Hong-Wen Deng Is replication the gold standard for validating genome-wide association findings? PLoS ONE |
| title | Is replication the gold standard for validating genome-wide association findings? |
| title_full | Is replication the gold standard for validating genome-wide association findings? |
| title_fullStr | Is replication the gold standard for validating genome-wide association findings? |
| title_full_unstemmed | Is replication the gold standard for validating genome-wide association findings? |
| title_short | Is replication the gold standard for validating genome-wide association findings? |
| title_sort | is replication the gold standard for validating genome wide association findings |
| url | http://europepmc.org/articles/PMC2605260?pdf=render |
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