Evidence map›Paper›PMID 21822022›Full record

ArticleHuman heredity2011

Unifying ideas for non-parametric linkage analysis.

Aaron G Day-Williams, John Blangero, Thomas D Dyer, Kenneth Lange, Eric M Sobel

Abstract read
In one paragraph

Article in Human heredity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

5 authors.

Aaron G Day-WilliamsDepartment of Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, USA. adw @ sanger.ac.uk
John Blangero
Thomas D Dyer
Kenneth Lange
Eric M Sobel

Funding

Quantitative Trait Locus Mapping in Human PedigreesR37MH059490 · NIMH · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI BLANGERO, JOHN · 2001 to 2010
$6.8M
NIMH NIH HHS R37 MH059490
6 · The paper itself

Abstract

objectivesNon-parametric linkage analysis (NPL) exploits marker allele sharing among affected relatives to map genes influencing complex traits. Computational barriers force approximate analysis on large pedigrees and the adoption of a questionable perfect data assumption (PDA) in assigning p values. To improve NPL significance testing on large pedigrees, we examine the adverse consequences of missing data and PDA. We also introduce a novel statistic, Q-NPL, appropriate for NPL analysis of quantitative traits.

methodsUsing simulated and real data sets with qualitative traits, we compare NPL analysis results for four testing procedures and various degrees of missing data. The simulated data sets vary from all nuclear families, to all large pedigrees, to a mix of pedigrees of different sizes. We implemented the Kong and Cox linear adjustment of p values in the software packages Mendel and SimWalk. We perform similar analysis with Q-NPL on quantitative traits of various heritabilities.

resultsThe Kong and Cox extension for significance testing is robust to realistic missing data patterns, greatly improves p values in approximate analyses, and works equally well for qualitative and quantitative traits and small and large pedigrees. The Q-NPL statistic is robust to missing data and shows good power to detect linkage for quantitative traits with a wide spectrum of heritabilities.

conclusionsThe Kong and Cox extension should be a standard tool for calculating NPL p values. It allows the combination of exact and estimated analyses into a single significance score. Q-NPL should be a standard statistic for NPL analysis of quantitative traits. The new statistics are implemented in Mendel and SimWalk.

Indexed as

Genetic LinkageChromosome MappingHumansPedigreeQuantitative Trait LociStatistics, Nonparametric

Identifiers

PMID21822022
PMCPMC7077094

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.