ArticleAmerican journal of human genetics2004
Inherent bias toward the null hypothesis in conventional multipoint nonparametric linkage analysis.
Article in American journal of human genetics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study.Schizophrenia research · 2016Review
- Heritability and linkage analysis of personality in bipolar disorder.Journal of affective disorders · 2013Article
- Heritability and genome-wide SNP linkage analysis of temperament in bipolar disorder.Journal of affective disorders · 2013Article
- Genome-wide linkage analyses of 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia.The American journal of psychiatry · 2013Article
- Unifying ideas for non-parametric linkage analysis.Human heredity · 2011Article
- Design considerations in a sib-pair study of linkage for susceptibility loci in cancer.BMC medical genetics · 2008Article
- Weighting affected sib pairs by marker informativity.American journal of human genetics · 2005Article
- A genomewide search using an original pairwise sampling approach for large genealogies identifies a new locus for total and low-density lipoprotein cholesterol in two genetically differentiated isolates of Sardinia.American journal of human genetics · 2004Article
- "Bias toward the null" means reduced power.American journal of human genetics · 2004Article
- Conventional multipoint nonparametric linkage analysis is not necessarily inherently biased.American journal of human genetics · 2004Article
- No "bias" toward the null hypothesis in most conventional multipoint nonparametric linkage analyses.American journal of human genetics · 2004Article
- No bias in linkage analysis.American journal of human genetics · 2004Article
- Bias toward the null hypothesis in model-free linkage analysis is highly dependent on the test statistic used.American journal of human genetics · 2004Article
- Large-scale integration of human genetic and physical maps.Genome research · 2004Article
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Abstract
Traditional nonparametric "multipoint" statistical procedures have been developed for assigning allele-sharing values at a locus of interest to pairs of relatives for linkage studies. These procedures attempt to accommodate a lack of informativity, nongenotyped loci, missing data, and related issues concerning the genetic markers used in a linkage study. However, such procedures often cannot overcome these phenomena in compelling ways and, as a result, assign relevant relative pairs allele-sharing values that are "expected" for those pairs. The practice of assigning expected allele-sharing values to relative pairs in the face of a lack of explicit allele-transmission information can bias traditional nonparametric linkage test statistics toward the null hypothesis of no locus effect. This bias is due to the use of expected values, rather than to a lack of information about actual allele sharing at relevant marker loci. The bias will vary from study to study on the basis of the DNA markers, sample size, relative-pair types, and pedigree structures used, but it can be extremely pronounced and could contribute to a lack of consistent success in the application of traditional nonparametric linkage analyses to complex human traits and diseases. There are several potential ways to overcome this problem, but their foundations deserve greater research. We expose many of the issues concerning allele sharing with data from a large affected-sibling-pair study investigating the genetic basis of autism.
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