Journal ArticleDOI
Power of the affected-sib-pair method to defect disease susceptibility loci of small effect: an application to multiple sclerosis.
Brian Suarez,Brian Suarez,Dennis H. O'Rourke,Dennis H. O'Rourke,Paul Van Eerdewegh,John M. Opitz +5 more
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TLDR
It is shown that compared to affected-sib-pairs, trios with the above configuration are less efficient in detecting the presence of a linked disease susceptibility locus.Abstract:
The distribution of marker locus identity-by-descent scores in affected sib pairs provides a powerful tool for detecting the presence of a linked non-Mendelian disease susceptibility locus. This basic approach is here extended to include a trio of sibs. A special type of sib trio consisting of two affected and one unaffected sib is investigated. It is shown that compared to affected-sib-pairs, trios with the above configuration are less efficient in detecting the presence of a linked disease susceptibility locus.
When the generalized two-allele single locus model is fitted to sib pairs affected with multiple sclerosis, an estimate of the recombination fraction of 0.21 between the putative disease susceptibility locus and the HLA complex is obtained. However, this transmission model is deemed inadequate since a recombination fraction this large is inconsistent with the variety of HLA associations observed at the population level.read more
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Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits
TL;DR: A website for performing power calculations for the design of linkage and association genetic mapping studies of complex traits and the package is made available atstatgen.iop.ac.uk/gpc.
Journal Article
Assessing the role of HLA-linked and unlinked determinants of disease
TL;DR: A single-locus model of disease susceptibility is rejected, implying the existence of additional unlinked familial determinants, and the relationship between increased risk in relatives over population prevalence and probability of sharing zero marker alleles identical by descent at a linked locus by an affected relative pair is examined.
Journal ArticleDOI
Hla class ii-associated genetic susceptibility in multiple sclerosis : a critical evaluation
Olle Olerup,Jan Hillert +1 more
TL;DR: These issues were investigated in a large group of Swedish MS patients and it was found that the associations with the suggested DQB1 sequences and position 34 of the DQ alpha chain were due to linkage disequilibrium and secondary to the association with the DRw15,DQw6,Dw2 haplotype.
Journal ArticleDOI
A comparison of sib-pair linkage tests for disease susceptibility loci
Blackwelder Wc,Elston Rc +1 more
TL;DR: It is shown it is valid to use the information from all possible sib pairs as though they came from separate families when data on sibships of size three or larger are available, though more power may be obtained if different weights are given to the different sibship sizes.
References
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Journal ArticleDOI
Histocompatibility determinants in multiple sclerosis, with special reference to clinical course
TL;DR: Family studies showed that the LD-7a character is inherited and not acquired, and the progression of the disease was significantly different from that observed in normal HL-A7 negatives.