ArticleAmerican journal of human genetics2006
The affected-/discordant-sib-pair design can guarantee validity of multipoint model-free linkage analysis of incomplete pedigrees when there is marker-marker disequilibrium.
Article in American journal of human genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Affected Sib-Pair Analyses Identify Signaling Networks Associated With Social Behavioral Deficits in Autism.Frontiers in genetics · 2019Article
- A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2012Article
- Linkage analysis with dense SNP maps in isolated populations.Human heredity · 2009Article
- Article
- Examining the effect of linkage disequilibrium between markers on the Type I error rate and power of nonparametric multipoint linkage analysis of two-generation and multigenerational pedigrees in the presence of missing genotype data.Genetic epidemiology · 2008Article
- Haseman-Elston regression in ascertained samples: importance of dependent variable and mean correction factor selection.Human heredity · 2008Article
- Two-step intermediate fine mapping with likelihood ratio test statistics: applications to Problems 2 and 3 data of GAW15.BMC proceedings · 2007Article
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Authors and funding
5 authors.
Funding
Abstract
Genomewide linkage studies are tending toward the use of single-nucleotide polymorphisms (SNPs) as the markers of choice. However, linkage disequilibrium (LD) between tightly linked SNPs violates the fundamental assumption of linkage equilibrium (LE) between markers that underlies most multipoint calculation algorithms currently available, and this leads to inflated affected-relative-pair allele-sharing statistics when founders' multilocus genotypes are unknown. In this study, we investigate the impact that the degree of LD, marker allele frequency, and association type have on estimating the probabilities of sharing alleles identical by descent in multipoint calculations and hence on type I error rates of different sib-pair linkage approaches that assume LE. We show that marker-marker LD does not inflate type I error rates of affected sib pair (ASP) statistics in the whole parameter space, and that, in any case, discordant sib pairs (DSPs) can be used to control for marker-marker LD in ASPs. We advocate the ASP/DSP design with appropriate sib-pair statistics that test the difference in allele sharing between ASPs and DSPs.
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