Comparison of methods for combining case-control and family-based association studies

Glaser, Beate and Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412 2009. Comparison of methods for combining case-control and family-based association studies. Human Heredity 68 (2) , pp. 106-116. 10.1159/000212503

Full text not available from this repository.

Abstract

OBJECTIVES: Combining the analysis of family-based samples with unrelated individuals can enhance the power of genetic association studies. Various combined analysis techniques have been recently developed; as yet, there have been no comparisons of their power, or robustness to confounding factors. We investigated empirically the power of up to six combined methods using simulated samples of trios and unrelated cases/controls (TDTCC), trios and unrelated controls (TDTC), and affected sibpairs with parents and unrelated cases/controls (ASPFCC). METHODS: We simulated multiplicative, dominant and recessive models with varying risk parameters in single samples. Additionally, we studied false-positive rates and investigated, if possible, the coverage of the true genetic effect (TDTCC). RESULTS/CONCLUSIONS: Under the TDTCC design, we identified four approaches with equivalent power and false-positive rates. Combined statistics were more powerful than single-sample statistics or a pooled chi(2)-statistic when risk parameters were similar in single samples. Adding parental information to the CC part of the joint likelihood increased the power of generalised logistic regression under the TDTC but not the TDTCC scenario. Formal testing of differences between risk parameters in subsamples was the most sensitive approach to avoid confounding in combined analysis. Non-parametric analysis based on Monte-Carlo testing showed the highest power for ASPFCC samples.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Karger
ISSN:	1423-0062
Last Modified:	31 Oct 2022 09:33
URI:	https://orca.cardiff.ac.uk/id/eprint/81537

Citation Data

Cited 11 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item