Nsengimana, J and Barrett, JH orcid.org/0000-0002-1720-7724 (2012) Analysis of genetic interactions involving maternal and offspring genotypes at different Loci: power simulation and application to testicular cancer. Genetic Epidemiology, 36 (6). pp. 612-621. ISSN 0741-0395
Abstract
The analyses of genetic interaction between maternal and offspring genotypes are usually conducted considering a single locus. Here, we propose testing maternal × offspring (M×O) and maternal × maternal (M×M) genotype interactions involving two unlinked loci. We reformulate the log-linear approach of analyzing cases and their parents (family trios) to accommodate two loci, fit fuller models to avoid confounding in a first analysis step and propose that the model be reduced to the most prominent effects in a second step. We conduct extensive simulations to assess the validity and power of this approach under various model assumptions. We show that the approach is valid and has good power to detect M×O and M×M interactions. For example, the power to detect a dominant interaction relative risk of 1.5 (both M×O and M×M) is 70% with 300 trios and approaches 100% with 1,000 trios. Unlike the main effects, M×O and M×M interactions are conditionally independent of mating types, and consequently, their power is not affected by missing paternal genotypes. When applied to single-locus M×O interaction, our method is as powerful as other existing methods. Applying the method to testicular cancer, we found a nominally significant M×M interaction between single nucleotide polymorphisms from C-Kit Ligand (KITLG) and Sex Hormone Binding Globulin (SHBG) using 210 families (relative risk 2.2, P = 0.03). This finding supports a role of maternal hormones in offspring testicular cancer and warrants confirmation in a larger dataset.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Algorithms; Female; Genetic Predisposition to Disease; Genotype; Humans; Linear Models; Male; Models, Genetic; Parents; Polymorphism, Single Nucleotide; Reproducibility of Results; Sex Hormone-Binding Globulin; Stem Cell Factor; Testicular Neoplasms |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Epidemiology and Biostatistics (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Sep 2017 13:18 |
Last Modified: | 07 Sep 2017 13:18 |
Status: | Published |
Publisher: | John Wiley & Sons Inc. |
Identification Number: | 10.1002/gepi.21655 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:111009 |