Genetic Analysis Workshop 14: Microsatellite and single-nucleotide polymorphism

Genetic Analysis Workshop 14: microsatellite and single-nucleotide polymorphism marker loci for genome-wide scans

Authors: Joan E Bailey-Wilson, Laura Almasy, Mariza de Andrade, Julia Bailey, Heike Bickeböller, Heather J Cordell, E Warwick Daw, Lynn Goldin, Ellen L Goode, Courtney Gray-McGuire, Wayne Hening, Gail Jarvik, Brion S Maher, Nancy Mendell, Andrew D Paterson, John Rice…

Description of the data from the Collaborative Study on the Genetics of Alcoholism (COGA) and single-nucleotide polymorphism genotyping for Genetic Analysis Workshop 14

The data provided to the Genetic Analysis Workshop 14 (GAW 14) was the result of a collaboration among several different groups, catalyzed by Elizabeth Pugh from The Center for Inherited Disease Research (CIDR...

Authors: Howard J Edenberg, Laura J Bierut, Paul Boyce, Manqiu Cao, Simon Cawley, Richard Chiles, Kimberly F Doheny, Mark Hansen, Tony Hinrichs, Kevin Jones, Mark Kelleher, Giulia C Kennedy, Guoying Liu, Gregory Marcus, Celeste McBride, Sarah Shaw Murray…

Construction of the model for the Genetic Analysis Workshop 14 simulated data: genotype-phenotype relationships, gene interaction, linkage, association, disequilibrium, and ascertainment effects for a complex phenotype

The Genetic Analysis Workshop 14 simulated dataset was designed 1) To test the ability to find genes related to a complex disease (such as alcoholism). Such a disease may be given a variety of definitions by d...

Authors: David A Greenberg, Junying Zhang, Dvora Shmulewitz, Lisa J Strug, Regina Zimmerman, Veena Singh and Sudhir Marathe

Genome scan linkage analysis comparing microsatellites and single-nucleotide polymorphisms markers for two measures of alcoholism in chromosomes 1, 4, and 7

We analyzed 143 pedigrees (364 nuclear families) in the Collaborative Study on the Genetics of Alcoholism (COGA) data provided to the participants in the Genetic Analysis Workshop 14 (GAW14) with the goal of c...

Authors: Guanjie Chen, Adebowale Adeyemo, Jie Zhou, Ao Yuan, Yuanxiu Chen and Charles Rotimi

Comparison of single-nucleotide polymorphisms and microsatellites in detecting quantitative trait loci for alcoholism: The Collaborative Study on the Genetics of Alcoholism

The feasibility of effectively analyzing high-density single nucleotide polymorphism (SNP) maps in whole genome scans of complex traits is not known. The purpose of this study was to compare variance component...

Authors: Helen Kim, Carolyn M Hutter, Stephanie A Monks and Karen L Edwards

The effect of linkage disequilibrium on linkage analysis of incomplete pedigrees

Dense SNP maps can be highly informative for linkage studies. But when parental genotypes are missing, multipoint linkage scores can be inflated in regions with substantial marker-marker linkage disequilibrium...

Authors: Douglas F Levinson and Peter Holmans

Comparison of the power between microsatellite and single-nucleotide polymorphism markers for linkage and linkage disequilibrium mapping of an electrophysiological phenotype

We performed linkage and linkage disequilibrium (LD) mapping analyses to compare the power between microsatellite and single nucleotide polymorphism (SNP) markers. Chromosome-wide analyses were performed for a...

Authors: Hsiu-Fen Lin, Suh-Hang Hank Juo and Rong Cheng

Genome-wide linkage analysis for alcohol dependence: a comparison between single-nucleotide polymorphism and microsatellite marker assays

Both theoretical and applied studies have proven that the utility of single nucleotide polymorphism (SNP) markers in linkage analysis is more powerful and cost-effective than current microsatellite marker assa...

Authors: Qianli Ma, Yi Yu, Yan Meng, John Farrell, Lindsay A Farrer and Marsha A Wilcox

Whole-genome association studies of alcoholism with loci linked to schizophrenia susceptibility

Alcoholism is a complex disease. There have been many reports on significant comorbidity between alcoholism and schizophrenia. For the genetic study of complex diseases, association analysis has been recommend...

Authors: Junghyun Namkung, Youngchul Kim and Taesung Park

Linkage analysis of complex diseases using microsatellites and single-nucleotide polymorphisms: application to alcoholism

The efficacy of linkage studies using microsatellites and single-nucleotide polymorphisms (SNPs) was evaluated. Analyzed data were supplied by the Collaborative Study on the Genetics of Alcoholism (COGA). Alco...

Authors: Jérémie Nsengimana, Hélène Renard and David Goldgar

Comparison of marker types and map assumptions using Markov chain Monte Carlo-based linkage analysis of COGA data

We performed multipoint linkage analysis of the electrophysiological trait ECB21 on chromosome 4 in the full pedigrees provided by the Collaborative Study on the Genetics of Alcoholism (COGA). Three Markov cha...

Authors: Weiva Sieh, Saonli Basu, Audrey Q Fu, Joseph H Rothstein, Paul A Scheet, William CL Stewart, Yun J Sung, Elizabeth A Thompson and Ellen M Wijsman

Genome-wide linkage analysis of age at onset of alcohol dependence: a comparison between microsatellites and single-nucleotide polymorphisms

Using the dataset provided for Genetic Analysis Workshop 14 by the Collaborative Study on the Genetics of Alcoholism, we performed genome-wide linkage analysis of age at onset of alcoholism to compare the util...

Authors: Bamidele O Tayo, Yulan Liang, Saverio Stranges and Maurizio Trevisan

Comparing single-nucleotide polymorphism marker-based and microsatellite marker-based linkage analyses

We compared linkage analysis results for an alcoholism trait, ALDX1 (DSM-III-R and Feigner criteria) using a nonparametric linkage analysis method, which takes into account allele sharing among several affecte...

Authors: Ayse Ulgen and Wentian Li

Linkage analysis of the GAW14 simulated dataset with microsatellite and single-nucleotide polymorphism markers in large pedigrees

Recent studies have suggested that a high-density single nucleotide polymorphism (SNP) marker set could provide equivalent or even superior information compared with currently used microsatellite (STR) marker ...

Authors: Xiaohong (Rose) Yang, Kevin Jacobs, Kimberly F Kerstann, Andrew W Bergen, Alisa M Goldstein and Lynn R Goldin

Whole-genome variance components linkage analysis using single-nucleotide polymorphisms versus microsatellites on quantitative traits of derived phenotypes from factor analysis of electroencephalogram waves

Alcohol dependence is a serious public health problem. We studied data from families participating in the Collaborative Study on the Genetics of Alcoholism (COGA) and made available to participants in the Gene...

Authors: Yi Yu, Yan Meng, Qianli Ma, John Farrell, Lindsay A Farrer and Marsha A Wilcox

Which strategy is better for linkage analysis: single-nucleotide polymorphisms or microsatellites? Evaluation by identity-by-state – identity-by-descent transformation affected sib-pair method on GAW14 data

The central issue for Genetic Analysis Workshop 14 (GAW14) is the question, which is the better strategy for linkage analysis, the use of single-nucleotide polymorphisms (SNPs) or microsatellite markers? To an...

Authors: Qingqi Yue, Victor Apprey and George E Bonney

A genome-wide linkage analysis of alcoholism on microsatellite and single-nucleotide polymorphism data, using alcohol dependence phenotypes and electroencephalogram measures

The Collaborative Study on the Genetics of Alcoholism (COGA) is a large-scale family study designed to identify genes that affect the risk for alcoholism and alcohol-related phenotypes. We performed genome-wid...

Authors: Chun Zhang, Simon Cawley, Guoying Liu, Manqiu Cao, Harley Gorrell and Giulia C Kennedy

Detection of susceptibility loci by genome-wide linkage analysis

The objective of this study is to evaluate the efficacy of a model-free linkage statistics for finding evidence of linkage using two different maps and to illustrate how the comparison of results from several ...

Authors: Marie-Claude Babron, Catherine Bourgain, Anne-Louise Leutenegger and Françoise Clerget-Darpoux

Linkage mapping of a complex trait in the New York population of the GAW14 simulated dataset: a multivariate phenotype approach

Multivariate phenotypes underlie complex traits. Thus, instead of using the end-point trait, it may be statistically more powerful to use a multivariate phenotype correlated to the end-point trait for detectin...

Authors: Saurabh Ghosh, Samsiddhi Bhattacharjee, Gourab Basu, Sandip Pal and Partha P Majumder

Investigation of altering single-nucleotide polymorphism density on the power to detect trait loci and frequency of false positive in nonparametric linkage analyses of qualitative traits

Genome-wide linkage analysis using microsatellite markers has been successful in the identification of numerous Mendelian and complex disease loci. The recent availability of high-density single-nucleotide pol...

Authors: Alison P Klein, Ya-Yu Tsai, Priya Duggal, Elizabeth M Gillanders, Michael Barnhart, Rasika A Mathias, Ian P Dusenberry, Amy Turiff, Peter S Chines, Janet Goldstein, Robert Wojciechowski, Wayne Hening, Elizabeth W Pugh and Joan E Bailey-Wilson

Interval estimation of disease loci: development and applications of new linkage methods

Three variants of the confidence set inference (CSI) procedure were proposed and applied to both the simulated and the Collaborative Study on the Genetics of Alcoholism (COGA) data. For each of the two applica...

Authors: Charalampos Papachristou and Shili Lin

Inclusion of unaffected sibs increases power in model-free linkage analysis of a behavioral trait

Study design strategies are of critical importance in the search for genes underlying complex diseases. Two important design choices in planning gene mapping studies are the analytic strategy to be used, which...

Authors: Sabine Plancoulaine, Alexandre Alcaïs, Yue Chen, Laurent Abel and France Gagnon

Local false discovery rate and minimum total error rate approaches to identifying interesting chromosomal regions

The simultaneous testing of a large number of hypotheses in a genome scan, using individual thresholds for significance, inherently leads to inflated genome-wide false positive rates. There exist various appro...

Authors: Ritwik Sinha, Moumita Sinha, George Mathew, Robert C Elston and Yuqun Luo

Resampling methods to reduce the selection bias in genetic effect estimation in genome-wide scans

Using the simulated data of Problem 2 for Genetic Analysis Workshop 14 (GAW14), we investigated the ability of three bootstrap-based resampling estimators (a shrinkage, an out-of-sample, and a weighted estimat...

Authors: Long Yang Wu, Sophia SF Lee, Haijiang Steven Shi, Lei Sun and Shelley B Bull

Linkage and association analyses of microsatellites and single-nucleotide polymorphisms in nuclear families

Several simulation studies have suggested that a high-density single-nucleotide polymorphisms (SNPs) marker set may be as useful as a traditional microsatellites (MS) marker set in performing whole-genome link...

Authors: Jennifer Lin and Kuang-Yu Liu

Comparison of single-nucleotide polymorphisms and microsatellites in inference of population structure

Single-nucleotide polymorphisms (SNPs) are a class of attractive genetic markers for population genetic studies and for identifying genetic variations underlying complex traits. However, the usefulness and eff...

Authors: Nianjun Liu, Liang Chen, Shuang Wang, Cheongeun Oh and Hongyu Zhao

A comparison between microsatellite and single-nucleotide polymorphism markers with respect to two measures of information content

Using the Genetic Analysis Workshop 14 (GAW14) simulated dataset, we compare microsatellite and single-nucleotide polymorphism (SNP) markers in terms of two measures of information content, the traditional ent...

Authors: Anbupalam Thalamuthu, Indranil Mukhopadhyay, Amrita Ray and Daniel E Weeks

Whole-genome linkage analysis in mapping alcoholism genes using single-nucleotide polymorphisms and microsatellites

There is currently a great interest in using single-nucleotide polymorphisms (SNPs) in genetic linkage and association studies because of the abundance of SNPs as well as the availability of high-throughput ge...

Authors: Shuang Wang, Song Huang, Nianjun Liu, Liang Chen, Cheongeun Oh and Hongyu Zhao

Comparison of microsatellites, single-nucleotide polymorphisms (SNPs) and composite markers derived from SNPs in linkage analysis

There is growing evidence that a map of dense single-nucleotide polymorphisms (SNPs) can outperform a map of sparse microsatellites for linkage analysis. There is also argument as to whether a clustered SNP ma...

Authors: Chao Xing, Fredrick R Schumacher, Guan Xing, Qing Lu, Tao Wang and Robert C Elston

A genome-wide scanning and fine mapping study of COGA data

A thorough genetic mapping study was performed to identify predisposing genes for alcoholism dependence using the Collaborative Study on the Genetics of Alcoholism (COGA) data. The procedure comprised whole-ge...

Authors: Hsin-Chou Yang, Chien-Ching Chang, Chin-Yu Lin, Chun-Liang Chen, Chin-Yu Lin and Cathy SJ Fann

Linkage analysis and association analysis in the presence of linkage using age at onset of COGA alcoholism data

Complex disease mapping usually involves a combination of linkage and association techniques. Linkage analysis can scan the entire genome in a few hundred tests. Association tests may involve an even greater n...

Authors: Xiaoyun Zhong and Heping Zhang

Single-nucleotide polymorphism versus microsatellite markers in a combined linkage and segregation analysis of a quantitative trait

Increasingly, single-nucleotide polymorphism (SNP) markers are being used in preference to microsatellite markers. However, methods developed for microsatellites may be problematic when applied to SNP markers....

Authors: E Warwick Daw, Simon C Heath and Yue Lu

Application of the propensity score in a covariate-based linkage analysis of the Collaborative Study on the Genetics of Alcoholism

Covariate-based linkage analyses using a conditional logistic model as implemented in LODPAL can increase the power to detect linkage by minimizing disease heterogeneity. However, each additional covariate ana...

Authors: Betty Q Doan, Constantine E Frangakis, Yin Y Shugart and Joan E Bailey-Wilson

Multipoint identity-by-descent computations for single-point polymorphism and microsatellite maps

We used the LOKI software to generate multipoint identity-by-descent matrices for a microsatellite map (with 31 markers) and two single-nucleotide polymorphism (SNP) maps to examine information content across ...

Authors: Anthony L Hinrichs, Sarah Bertelsen, Laura J Bierut, Gerald Dunn, Carol H Jin, John S Kauwe and Brian K Suarez

Simulation-based homozygosity mapping with the GAW14 COGA dataset on alcoholism

We have developed a simulation-based approach to the analysis of shared homozygous chromosomal segments and have applied it to data on allele sharing among alcoholics in a single Collaborative Study on the Gen...

Authors: Ondrej Libiger and Nicholas J Schork

Linkage analysis of alcohol dependence using both affected and discordant sib pairs

The basic idea of affected-sib-pair (ASP) linkage analysis is to test whether the inheritance pattern of a marker deviates from Mendelian expectation in a sample of ASPs. The test depends on an assumed Mendeli...

Authors: Pei-Ying Shih, Tao Wang, Chao Xing, Moumita Sinha, Yeunjoo Song and Robert C Elston

Multilocus and interaction-based genome scan for alcoholism risk factors in Caucasian Americans: the COGA study

In this paper, we applied the nonparametric linkage regression approach to the Caucasian genome scan data from the Collaborative Study on the Genetics of Alcoholism to search for regions of the genome that exh...

Authors: Adrienne H Williams, W Mark Brown and Carl D Langefeld

Recursive partitioning models for linkage in COGA data

We have developed a recursive-partitioning (RP) algorithm for identifying phenotype and covariate groupings that interact with the evidence for linkage. This data-mining approach for detecting gene × environme...

Authors: Wei Xu, Chelsea Taylor, Justin Veenstra, Shelley B Bull, Mary Corey and Celia MT Greenwood

A Bayesian approach for applying Haseman-Elston methods

The main goal of this paper is to couple the Haseman-Elston method with a simple yet effective Bayesian factor-screening approach. This approach selects markers by considering a set of multigenic models that i...

Authors: Seungtai Yoon, Young Ju Suh, Nancy Role Mendell and Kenny Qian Ye

Linkage analysis of GAW14 simulated data: comparison of multimarker, multipoint, and conditional approaches

The purposes of this study were 1) to examine the performance of a new multimarker regression approach for model-free linkage analysis in comparison to a conventional multipoint approach, and 2) to determine t...

Authors: Mathew J Barber, Eleanor Wheeler and Heather J Cordell

Genome-wide linkage and association mapping of disease genes with the GAW14 simulated datasets

We combined the results of whole-genome linkage and association analyses to determine which markers were most strongly associated with Kofendrerd Personality Disorder. Using replicate 1 from the Genetic Analys...

Authors: Kim W Carter, Pamela A McCaskie and Lyle J Palmer

Identifying genomic regions for fine-mapping using genome scan meta-analysis (GSMA) to identify the minimum regions of maximum significance (MRMS) across populations

In order to detect linkage of the simulated complex disease Kofendrerd Personality Disorder across studies from multiple populations, we performed a genome scan meta-analysis (GSMA). Using the 7-cM microsatell...

Authors: Margaret E Cooper, Toby H Goldstein, Brion S Maher and Mary L Marazita

An updated meta-analysis approach for genetic linkage

We present a meta-analysis procedure for genome-wide linkage studies (MAGS). The MAGS procedure combines genome-wide linkage results across studies with possibly distinct marker maps. We applied the MAGS proce...

Authors: Carol J Etzel, Mei Liu and Tracy J Costello

Calculation of multipoint likelihoods using flanking marker data: a simulation study

The calculation of multipoint likelihoods is computationally challenging, with the exact calculation of multipoint probabilities only possible on small pedigrees with many markers or large pedigrees with few m...

Authors: Andrew W George, LaVonne A Mangin, Christopher W Bartlett, Mark W Logue, Alberto M Segre and Veronica J Vieland

Covariate linkage analysis of GAW14 simulated data incorporating subclinical phenotype, sex, population, parent-of-origin, and interaction

We evaluate a method for the incorporation of covariates into linkage analysis using the Genetic Analysis Workshop 14 simulated data. Focusing on a randomly chosen replicate (42) we investigated the effect of ...

Authors: Marian L Hamshere, Stuart MacGregor, Valentina Moskvina, Ivan N Nikolov and Peter A Holmans

Modeling the effect of an associated single-nucleotide polymorphism in linkage studies

For linkage analysis in affected sibling pairs, we propose a regression model to incorporate information from a disease-associated single-nucleotide polymorphism located under the linkage peak. This model can ...

Authors: Jeanine J Houwing-Duistermaat, Hae-Won Uh, Jeremie JP Lebrec, Hein Putter and Li Hsu

A gene-model-free method for linkage analysis of a disease-related-trait based on analysis of proband/sibling pairs

In this paper we investigate the power of finding linkage to a disease locus through analysis of the disease-related traits. We propose two family-based gene-model-free linkage statistics. Both involve conside...

Authors: Heejong Sung, Stephen J Finch, Kenny Q Ye and Nancy R Mendell

The role of parametric linkage methods in complex trait analyses using microsatellites

Many investigators of complexly inherited familial traits bypass classical segregation analysis to perform model-free genome-wide linkage scans. Because model-based or parametric linkage analysis may be the mo...

Authors: Michael D Badzioch, Ellen L Goode and Gail P Jarvik

Including endophenotypes as covariates in variance component heritability and linkage analysis

The purpose of these analyses was to determine if incorporating or adjusting for covariates in genetic analyses helped or hindered in genetic analyses, specifically heritability and linkage analyses. To study ...

Authors: Julia N Bailey

Haseman-Elston weighted by marker informativity

In the Haseman-Elston approach the squared phenotypic difference is regressed on the proportion of alleles shared identical by descent (IBD) to map a quantitative trait to a genetic marker. In applications the...

Authors: Daniel Franke, André Kleensang, Robert C Elston and Andreas Ziegler