A genomic imprinting test for ordinal traits in pedigree data.
Genomic imprinting can lead maternally and paternally derived alleles with identical nucleotide sequences to function differently and has been found to affect the complex inheritance of a variety of human disorders. Statistical methods that differentiate the parent-of-origin effects on human diseases are available for binary traits and continuous traits. However, numerous common diseases are measured on discrete ordinal scales. Imprinting may also contribute to the complex genetic basis of these traits. In a previous study, we proposed a latent variable model and developed computationally efficient score statistic to test linkage of ordinal traits for any size pedigree while adjusting for non-genetic covariates. In this study, we extend the latent variable model to incorporate parent-of-origin information and further develop a score statistic for testing the imprinting effect in linkage analysis. We evaluated the properties of our test statistic using simulations. We then applied our method to the Collaborative Study on the Genetics of Alcoholism and found a novel locus on chromosome 18 that shows a strong signal for imprinting. In addition, we identified two loci on chromosomes 3 and 4 significantly (p<0.0001) linked with alcoholism.
Feng
Rui
R
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA. rfeng@ms.soph.uab.edu
Zhang
Heping
H
D000437:Alcoholism / Q000235:genetics; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D010375:Pedigree