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Title of Journal: Sci China Math

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Abbravation: Science China Mathematics

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SP Science China Press

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DOI

10.1016/j.amepre.2011.04.013

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1869-1862

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Correcting for biases in affected sibpair linkage

Authors: Min Yuan WenQuan Cui YaNing Yang
Publish Date: 2012/02/19
Volume: 55, Issue: 6, Pages: 1127-1135
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Abstract

When there is uncertainty in sibling relationship the classical affected sibpair ASP linkage tests may be severely biased This can happen for example if some of the half sibpairs are mixed with full sibpairs The genomic control method has been used in association analysis to adjust for population structures We show that the same idea can be applied to ASP linkage analysis with uncertainty in sibling relationship Assuming that in addition to the candidate marker null markers that are unlinked to the disease locus are also genotyped we may use the information on these loci to estimate the proportion of half sibpairs and to correct for the bias and variance distortion caused by the heterogeneity of sibling relationship Unlike in association studies the null loci are not required to be matched with the candidate marker in allele frequency for ASP linkage analysis This makes our approach flexible in selecting null markers In our simulations using a number of 30 or more null loci can effectively remove the bias and variance distortion It is also shown that even the null loci are weakly linked to the disease locus the proposed method can also provide satisfactory correction

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