Assessment of parent-of-origin effects in linkage analysis of quantitativetraits

Methods are presented for incorporation of parent-of-origin effects into li nkage analysis of quantitative traits. The estimated proportion of marker a lleles shared identical by descent is first partitioned into a component de rived from the mother and a component derived from the father. These parent -specific estimates of allele sharing are used in variance-components or Ha seman-Elston methods of linkage analysis so that the effect of the quantita tive-trait locus carried on the maternally derived chromosome is potentiall y different from the effect of the locus on the paternally derived chromoso me. Statistics for linkage between trait and marker loci derived from eithe r or both parents are then calculated, as are statistics for testing whethe r the effect of the maternally derived locus is equal to that of the patern ally derived locus. Analyses of data simulated for 956 siblings from 263 nu clear families who had participated in a linkage study revealed that type I error rates for these statistics were generally similar to nominal values. Power to detect an imprinted locus was substantially increased when analyz ed with a model allowing for parent-of-origin effects, compared with analys es that assumed equal effects; for example, for an imprinted locus accounti ng for 30% of the phenotypic variance, the expected LOD score was 4.5 when parent-of-origin effects were incorporated into the analysis, compared with 3.1 when these effects were ignored. The ability to include parent-of-orig in effects within linkage analysis of quantitative traits will facilitate g enetic dissection of complex traits.