Lescai, F;
Franceschi, C;
(2010)
The Impact of Phenocopy on the Genetic Analysis of Complex Traits.
PLOS ONE
, 5
(7)
, Article e11876. 10.1371/journal.pone.0011876.
![[thumbnail of 120675.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/application_pdf.png) Preview |
PDF
120675.pdf Download (1MB) |
Abstract
A consistent debate is ongoing on genome-wide association studies (GWAs). A key point is the capability to identify low-penetrance variations across the human genome. Among the phenomena reducing the power of these analyses, phenocopy level (PE) hampers very seriously the investigation of complex diseases, as well known in neurological disorders, cancer, and likely of primary importance in human ageing. PE seems to be the norm, rather than the exception, especially when considering the role of epigenetics and environmental factors towards phenotype. Despite some attempts, no recognized solution has been proposed, particularly to estimate the effects of phenocopies on the study planning or its analysis design. We present a simulation, where we attempt to define more precisely how phenocopy impacts on different analytical methods under different scenarios. With our approach the critical role of phenocopy emerges, and the more the PE level increases the more the initial difficulty in detecting gene-gene interactions is amplified. In particular, our results show that strong main effects are not hampered by the presence of an increasing amount of phenocopy in the study sample, despite progressively reducing the significance of the association, if the study is sufficiently powered. On the opposite, when purely epistatic effects are simulated, the capability of identifying the association depends on several parameters, such as the strength of the interaction between the polymorphic variants, the penetrance of the polymorphism and the alleles (minor or major) which produce the combined effect and their frequency in the population. We conclude that the neglect of the possible presence of phenocopies in complex traits heavily affects the analysis of their genetic data.
| Type: | Article |
|---|---|
| Title: | The Impact of Phenocopy on the Genetic Analysis of Complex Traits |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0011876 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0011876 |
| Language: | English |
| Additional information: | © 2010 Lescai, Franceschi. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The study has been supported under running costs funding of the university. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | GENOME-WIDE ASSOCIATION, MULTIFACTOR-DIMENSIONALITY REDUCTION, SUSCEPTIBILITY LOCUS, HUMAN-DISEASE, EPISTASIS, PATTERNS, CANCER, SCAN, HETEROGENEITY, REPLICATION |
| UCL classification: | UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/120675 |
Archive Staff Only
 |
View Item |
