A flexible model for association analysis in sibships with missing genotype data

Dudbridge, Frank, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412 and Wilson, Scott G. 2011. A flexible model for association analysis in sibships with missing genotype data. Annals of Human Genetics 75 (3) , pp. 428-438. 10.1111/j.1469-1809.2010.00636.x

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Abstract

A common design in family-based association studies consists of siblings without parents. Several methods have been proposed for analysis of sibship data, but they mostly do not allow for missing data, such as haplotype phase or untyped markers. On the other hand, general methods for nuclear families with missing data are computationally intensive when applied to sibships, since every family has missing parents that could have many possible genotypes. We propose a computationally efficient model for sibships by conditioning on the sets of alleles transmitted into the sibship by each parent. This means that the likelihood can be written only in terms of transmitted alleles and we do not have to sum over all possible untransmitted alleles when they cannot be deduced from the siblings. The model naturally accommodates missing data and admits standard theory of estimation, testing, and inclusion of covariates. Our model is quite robust to population stratification and can test for association in the presence of linkage. We show that our model has similar power to FBAT for single marker analysis and improved power for haplotype analysis. Compared to summing over all possible untransmitted alleles, we achieve similar power with considerable reductions in computation time.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QH Natural history > QH426 Genetics
Uncontrolled Keywords:	family-based association, TDT, sib-TDT, FBAT, haplotype
Publisher:	Wiley
ISSN:	0003-4800
Last Modified:	20 Oct 2022 08:05
URI:	https://orca.cardiff.ac.uk/id/eprint/27184

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