Last edited by Vogrel
Thursday, July 23, 2020 | History

2 edition of Family-based nonparametric tests of linkage and association. found in the catalog.

Family-based nonparametric tests of linkage and association.

Juan Pablo Lewinger

Family-based nonparametric tests of linkage and association.

by Juan Pablo Lewinger

  • 95 Want to read
  • 36 Currently reading

Published .
Written in English


About the Edition

We propose a general framework for constructing nonparametric tests of linkage sensitive to allelic association as well as tests of allelic association in the presence of linkage. These tests make efficient use of all information available in nuclear families, including family structure, unaffected offspring, parental phenotypes, families with both parents homozygous and families with missing parental genotypes. The non-parametric property of these tests is obtained by conditioning on sufficient statistics for the hypotheses of no linkage or no allelic association, according to the framework developed by Rabinowitz et al. [37]. The test statistics are conditional likelihood ratios based on a parametric model of marker and trait data that includes allelic association, and where model parameters are estimated from the sufficient statistic under the null hypothesis in what is essentially a segregation analysis.Family-based tests of linkage that are sensitive to the presence of allelic association between a marker and disease loci have become a popular alternative to case-control based tests of allelic association. These tests can be more powerful than allele-sharing tests if the level of allelic association is high. Because they are not sensitive to allelic associations that do not occur in conjunction with linkage they are immune to the "population stratification problem". Many of these tests are also nonparametric tests of linkage thus providing protection against violation of assumptions commonly made in parametric linkage analysis such as random mating, Hardy-Weinberg equilibrium, monogenic disease or allelic homogeneity. The simplest and best known test of this class is the transmission disequilibrium test (TDT) introduced by Spielman et al. [47]. Since its introduction in 1993 a large number of generalizations have been proposed to address some of the TDT"s original limitations. However most of these extensions discard valuable information.The performance of an implementation of these tests based on the standard two point linkage model is evaluated through Monte Carlo simulations, and applied in a study of hypertension. We also propose easy to implement Monte Carlo methods to compute power and p-values for a large class of family-based tests of linkage and association, including the ones we proposed.

The Physical Object
Pagination128 leaves.
Number of Pages128
ID Numbers
Open LibraryOL20338993M
ISBN 100612916480

This unique textbook guides students and researchers of social sciences to successfully apply the knowledge of parametric and nonparametric statistics in the collection and analysis of data. This book comprehensively covers all the methods of parametric and nonparametric statistics such as correlation and regression, analysis of variance, test construction, one-sample test to k-sample tests. What would be a good book for non-parametric statistics. Not just the introduction but advanced level. There are some problems included at the end of each section; you could definitely use the book to learn nonparametric statistics. For a treatment that is much more introductory: Higgins, J. (). Kruskal-Wallis and that bundle of.

Genetic linkage and association analyses are the major tools to identify the genetic basis of diseases or traits. The primary difference between these two approaches is that linkage analysis looks at the relation between the transmission of a locus and the disease/trait within families, whereas association analysis focuses on the relation between a specific allele and the disease/trait within. Nonparametric statistics is the branch of statistics that is not based solely on parametrized families of probability distributions (common examples of parameters are the mean and variance). Nonparametric statistics is based on either being distribution-free or having a specified distribution but with the distribution's parameters unspecified.

  As an exploratory approach, we apply an association test based on a modified family-based association test statistic to all rare variants (frequency association tests correctly identified causal single-nucleotide polymorphisms for four genes (KDR, VEGFA, VEGFC, and FLT1). Linkage Analysis vs Association Analysis Linkage studies are used when you have pedigrees of related individuals. Meanwhile the traits (phenotype) perform in some but not all of the family members. Thus, all the members including parents and children, no matter that wether they do or do not perform the phenotype, they have the same Size: KB.


Share this book
You might also like
Regulations for the Connecticut home guard.

Regulations for the Connecticut home guard.

Hertfordshire county structure plan.

Hertfordshire county structure plan.

specimen of papal and French persecution

specimen of papal and French persecution

Education, social, and moral reform, proportional representation

Education, social, and moral reform, proportional representation

Parking in relation to recreational needs

Parking in relation to recreational needs

Using Arabic synonyms

Using Arabic synonyms

Bible Impact-04-Lg:

Bible Impact-04-Lg:

Adventuring In The San Francisco Bay Area

Adventuring In The San Francisco Bay Area

Teacher supply and demand in the United States

Teacher supply and demand in the United States

Hartsville nuclear plants

Hartsville nuclear plants

Six miles to town

Six miles to town

Methods engineering

Methods engineering

Family-based nonparametric tests of linkage and association by Juan Pablo Lewinger Download PDF EPUB FB2

The large literature on family-based tests of association and/or linkage is reviewed, concentrating on the underlying principles and on recent methodological developments. Nonparametric, model‐free or weakly parametric linkage methods make fewer assumptions about the trait model.

Family‐based linkage analysis in general is most powerful to detect genetic variants that have large effects on risk of a disease or variation of a quantitative by:   Family-based association tests — FBAT and PDT. Often, nuclear families with multiple affected and unaffected siblings are collected and used to carry out both genetic linkage and association Cited by: With a family-based test (FBAT), the null and alternative hypotheses can be phrased in terms of the underlying genetics in the H0: no linkage or no association between the marker and any DSL underlying the trait.

Family-Based Methods for Linkage and Association Nonparametric Linkage Analysis using MERLIN The " --npl " option in MERLIN is straightforward to use, and gives a Kong and Cox style lod score nonparametric analysis.

The Kong and Cox exponential model is the default, and is thought to be more robust than the original linear model. Disease gene mapping is the first step towards our ultimate goal for understanding the etiology of a disease. Family-based linkage analysis and population-based association studies have been combining successfully as the workhorses for hunting disease genes in the past decades and are performed by: 1.

Family‐based designs require specialized analytic methods but they have distinct advantages: They are robust to confounding and variance inflation, which can arise in standard designs in the presence of population substructure; they test for both linkage and association; and they offer a natural solution to the multiple comparison by: We describe three popular model-free linkage analysis methods, the nonparametric linkage (NPL) statistic, the affected sib-pair (ASP) likelihood ratio test, and a likelihood approach for pedigrees.

Family based linkage • Assume heterozygosity for any disease individual (disease causing allele is rare). • We have a locus with alleles {1,2}. • The question is whether this locus is ‘linked’ to the disease.

In other words, does inheriting a specific allele at the locus make you more or less likely to have the disease. 'perm'/'mperm=' requests a family-based adaptive or max(T) permutation test. ' perm-count ' has the usual meaning.

By default, the permutation test statistic is the basic TDT p-value; ' parentdt1 '/' parentdt2 ' cause parenTDT or combined test. As a compromise between linkage studies and population-based association studies, family-based association designs can have similar power with population-based designs and are robust in the presence of population stratification.

Therefore, family-based association designs have received great attention by: Lewinger JP, Bull SB. A powerful test of linkage in the presence of association for nuclear families with arbitrary patterns of missing information [abstract] Am J Hum Genet. ; Lewinger JP. PhD thesis. University of Toronto, Department of Statistics; Family-based nonparametric tests of linkage and by: 4.

ilies.4,12–16 In addition to using family-based RV associa-tion methods to identify disease loci, linkage analysis can also be performed. Although parametric linkage analysis is inappropriate for complex trait analysis, non-parametric linkage (NPL)17 (also known as model free or allele sharing methods) is a powerful approach to identify.

The chi-square goodness of fit test, the association test and many other frequently used tests in genetics are nonparametric. statistics, parametric methods in statistics, robustness, see also above-mentioned tests for description and use, distribution-free, Kruskal-Wallis test; Kruglyak L et al Am J Hum Genet A genome-wide non-parametric linkage (NPL) study and four targeted fine-mapping family-based association studies were performed to locate the genes predisposing to PCD in Canadian families with multiple affected members.

the authors pointed out that linkage studies had less power than association studies to detect weak genetic effects exhibited by the loci involved in complex diseases. Not quite that general. More speci cally, the authors compared two speci c methods of linkage and association File Size: KB.

test statistic by combing the P-values of the family-based test with the rank-based P-values of the population-based test (Won et al.

In this article, we propose a nonparametric statistical framework, family-U, for family-based association analysis. Similar to conventional family-based methods, it Cited by: 2. To analyze family-based whole-genome sequence (WGS) data for complex traits, we developed a rare variant (RV) non-parametric linkage (NPL) analysis method, which has advantages over association methods.

The RV-NPL differs from the NPL in that RVs are analyzed, and allele sharing among affected relative-pairs is estimated only for minor : Linhai Zhao, Zongxiao He, Di Zhang, Gao T. Wang, Alan E. Renton, Badri N. Vardarajan, Michael Nothna.

FBAT, or the Family Based Association Test, is a test for association in the presence of linkage. FBAT has the advantage over conventional TDT of Cited by:   A statistical test, in which specific assumptions are made about the population parameter is known as the parametric test.

A statistical test used in the case of non-metric independent variables is called nonparametric test. In the parametric test, the test statistic is based. Family based genome-wide association test was also conducted using the SNPs. Results Nonparametric linkage analysis revealed weak linkage evidence on chromosome 7, and association analysis identified SNP tsc on chromosome 3 as significantly associated with by: Am.

J. Hum. Genet. –, Family-Based Tests of Association in the Presence of Linkage Stephen L. Lake, 1Deborah Blacker,2,3 and Nan M. Laird Departments of 1Biostatistics and 2Epidemiology, Harvard School of Public Health, and 3Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Harvard University, Boston.Even when standard linkage tests fail to provide evidence, however, a disease locus linked to the marker may be suggested sometimes by the presence of a "disease association," usually established by a case-control study.

Sorin Istrail The Transmission Disequilibrium Test (TDT) and GWASFile Size: KB.