Multipoint oligogenic analysis of age-at-onset data with applications to Alzheimer disease pedigrees

Article Abstract:

Monte Carlo Markov chain sampling is a suitable method for dealing with genetic aspects of diseases with onset in later years of life. Frequently such diseases have complex inheritance modes making it difficult to localize genes that are related. Usually recent generations and no others are available to be genotyped and phenotyped. With Monte Carlo Markov chain sampling, age at onset is regarded as a right-censored quantitative trait. Methods previously used are expanded and illustrated using an Alzheimer's disease data set. The sizes, number, allele frequencies and positions of quantitative trait loci (QTLs) are estimated. The QTLs are assumed to be diallelic and to interact in an additive fashion and the simultaneous multipoint segregation and linkage analysis method is effectively put into action.

Health aspects, Aged, Elderly, Methods, Measurement, Chromosome mapping, Health surveys, Monte Carlo method, Monte Carlo methods, Disease susceptibility, Quantitative genetics, Statistics (Mathematics)

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Genetic association mapping based on discordant sib pairs: the discordant-alleles test

Article Abstract:

Several family-based tests of association have been developed using discordant sib pairs (DSPs), those in which one sib is affected with a disease and the other is not. The tests are based on statistics that compare counts of alleles or genotypes or that test for symmetry in tables of genotypes or alleles. A permutation framework was used to assess the significance of the statistics obtained. For late-onset diseases methods that require genotypes on affected persons and their parents may not be suitable. The properties of the DSP-based tests have been compared by computer simulations. An application to Alzheimer's disease and the apolipoprotein E (apoE) polymorphism is illustrative. The discordant-alleles test seems to be the most powerful among those considered.

Research, Genetic disorders, Geriatrics, Allelomorphism, Alleles, Brothers and sisters

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