Genetic association with multiple traits in the presence of population stratification.

Abstract:

:Testing association between a genetic marker and multiple-dependent traits is a challenging task when both binary and quantitative traits are involved. The inverted regression model is a convenient method, in which the traits are treated as predictors although the genetic marker is an ordinal response. It is known that population stratification (PS) often affects population-based association studies. However, how it would affect the inverted regression for pleiotropic association, especially with the mixed types of traits (binary and quantitative), is not examined and the performance of existing methods to correct for PS using the inverted regression analysis is unknown. In this paper, we focus on the methods based on genomic control and principal component analysis, and investigate type I error of pleiotropic association using the inverted regression model in the presence of PS with allele frequencies and the distributions (or disease prevalences) of multiple traits varying across the subpopulations. We focus on common alleles but simulation results for a rare variant are also reported. An application to the HapMap data is used for illustration.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Yan T,Li Q,Li Y,Li Z,Zheng G

doi

10.1002/gepi.21738

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

571-80

issue

6

eissn

0741-0395

issn

1098-2272

journal_volume

37

pub_type

杂志文章
  • Accounting for population stratification in DNA methylation studies.

    abstract::DNA methylation is an important epigenetic mechanism that has been linked to complex diseases and is of great interest to researchers as a potential link between genome, environment, and disease. As the scale of DNA methylation association studies approaches that of genome-wide association studies, issues such as popu...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21789

    authors: Barfield RT,Almli LM,Kilaru V,Smith AK,Mercer KB,Duncan R,Klengel T,Mehta D,Binder EB,Epstein MP,Ressler KJ,Conneely KN

    更新日期:2014-04-01 00:00:00

  • Evidence for further breast cancer susceptibility genes in addition to BRCA1 and BRCA2 in a population-based study.

    abstract::We used data from a population based series of breast cancer patients to investigate the genetic models that can best explain familial breast cancer not due to the BRCA1 and BRCA2 genes. The data set consisted of 1,484 women diagnosed with breast cancer under age 55 registered in the East Anglia Cancer registry betwee...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1014

    authors: Antoniou AC,Pharoah PD,McMullan G,Day NE,Ponder BA,Easton D

    更新日期:2001-07-01 00:00:00

  • Haplotype variation and genotype imputation in African populations.

    abstract::Sub-Saharan Africa has been identified as the part of the world with the greatest human genetic diversity. This high level of diversity causes difficulties for genome-wide association (GWA) studies in African populations-for example, by reducing the accuracy of genotype imputation in African populations compared to no...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20626

    authors: Huang L,Jakobsson M,Pemberton TJ,Ibrahim M,Nyambo T,Omar S,Pritchard JK,Tishkoff SA,Rosenberg NA

    更新日期:2011-12-01 00:00:00

  • Analysis of twin data ascertained through probands: the double-entry approach.

    abstract::Twin pairs are sometimes included in studies because at least one of them is a proband, and conventionally the analysis of the data is based on the conditional distribution of the co twin given the proband. In the case of more than one proband in each pair, an often used "ad hoc" method of analysis is to allow each tw...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10253

    authors: Hindsberger C,Bryld LE

    更新日期:2003-11-01 00:00:00

  • TDT with covariates and genomic screens with mod scores: their behavior on simulated data.

    abstract::We describe an extension to the TDT (transmission/disequilibrium test) which allows for more than two marker alleles and for covariates measured on the parent or offspring. We also describe a systematic genomic search where the mod score (maximized lod score) is computed for each marker under constraints on the popula...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370120623

    authors: Rice JP,Neuman RJ,Hoshaw SL,Daw EW,Gu C

    更新日期:1995-01-01 00:00:00

  • Multipoint analysis using affected sib pairs: incorporating linkage evidence from unlinked regions.

    abstract::In this paper, we proposed a multipoint method to assess evidence of linkage to one region by incorporating linkage evidence from another region. This approach uses affected sib pairs in which the number of alleles shared identical by descent (IBD) is the primary statistic. This generalized estimating equation (GEE) a...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1021

    authors: Liang KY,Chiu YF,Beaty TH,Wjst M

    更新日期:2001-09-01 00:00:00

  • Genetic epidemiology of Menkes disease.

    abstract::Copper incorporation studies were performed on individuals from 58 pedigrees, comprising 140 sibships. As previously reported, there is considerable overlap between heterozygotes and normal homozygotes. Segregation analysis supports recessive inheritance of disease, with residual heritability for 64Cu uptake in cultur...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370030403

    authors: Horn N,Morton NE

    更新日期:1986-01-01 00:00:00

  • Propensity score-based nonparametric test revealing genetic variants underlying bipolar disorder.

    abstract::Association analysis has led to the identification of many genetic variants for complex diseases. While assessing the association between genes and a disease, other factors can play an important role. The consequence of not considering covariates (such as population stratification and environmental factors) is well-do...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20558

    authors: Jiang Y,Zhang H

    更新日期:2011-02-01 00:00:00

  • Association and linkage analysis of ICD-10 diagnosis for alcoholism.

    abstract::We analyzed the GAW11 data on alcoholism provided by the Collaborative Study on the Genetics of Alcoholism (COGA) using an extension of a new test of linkage and association for quantitative traits developed by George et al. [1999]. This method determines linkage between marker loci and quantitative traits, when allel...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370170758

    authors: Tiwari HK,Zhu X,Elston RC,Shu Y,George V

    更新日期:1999-01-01 00:00:00

  • Comparison of variance components, ANOVA and regression of offspring on midparent (ROMP) methods for SNP markers.

    abstract::An extension of the traditional regression of offspring on midparent (ROMP) method was used to estimate the heritability of the trait, test for marker association, and estimate the heritability attributable to a marker locus. The fifty replicates of the Genetic Analysis Workshop (GAW) 12 simulated general population d...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s794

    authors: Pugh EW,Papanicolaou GJ,Justice CM,Roy-Gagnon MH,Sorant AJ,Kingman A,Wilson AF

    更新日期:2001-01-01 00:00:00

  • Genetic analysis of IDDM: summary of GAW5 IDDM results.

    abstract::This paper summarizes the analyses by participants in the insulin-dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5). The data were obtained from 94 families with two or more IDDM sibs. Topics treated in the Workshop analysis included the following: methods for detecting associations an...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章,评审

    doi:10.1002/gepi.1370060111

    authors: Spielman RS,Baur MP,Clerget-Darpoux F

    更新日期:1989-01-01 00:00:00

  • Effect of polygenes on Xiong's transmission disequilibrium test of a QTL in nuclear families with multiple children.

    abstract::The transmission disequilibrium test (TDT), originally developed for mapping disease genes, has recently been extended to identify quantitative trait loci (QTL). For quantitative traits important for human health, generally multiple QTLs are involved. In the investigation of the statistical properties of the TDT, back...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1032

    authors: Deng HW,Li J,Recker RR

    更新日期:2001-11-01 00:00:00

  • Adaptive testing for association between two random vectors in moderate to high dimensions.

    abstract::Testing for association between two random vectors is a common and important task in many fields, however, existing tests, such as Escoufier's RV test, are suitable only for low-dimensional data, not for high-dimensional data. In moderate to high dimensions, it is necessary to consider sparse signals, which are often ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22059

    authors: Xu Z,Xu G,Pan W,Alzheimer's Disease Neuroimaging Initiative.

    更新日期:2017-11-01 00:00:00

  • Availability of schizophrenic patients and their families for genetic linkage studies: findings from the Maryland epidemiology sample.

    abstract::It has been suggested that collections of affected sib pairs, or their nuclear families, may be an efficient method for screening for genetic linkages in schizophrenia. We present the data collected in five years from 15 hospitals in the state of Maryland in an effort to determine if such a collection scheme will be f...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370060604

    authors: Pulver AE,Bale SJ

    更新日期:1989-01-01 00:00:00

  • Logistic transmission modeling for the simulated data of GAW10 problem 2.

    abstract::A recently developed nonparametric method is a generalization of the transmission disequilibrium test across all alleles of a locus. This approach has been applied to Problem 2 of GAW10 and has been extended to explore the combined contribution of neighboring loci for chromosomes 1, 5, and 8. When applied to the chrom...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1997)14:6<857::AID-GEPI49>

    authors: Neas BR,Moser KL,Harley JB

    更新日期:1997-01-01 00:00:00

  • Inflated type I error rates when using aggregation methods to analyze rare variants in the 1000 Genomes Project exon sequencing data in unrelated individuals: summary results from Group 7 at Genetic Analysis Workshop 17.

    abstract::As part of Genetic Analysis Workshop 17 (GAW17), our group considered the application of novel and standard approaches to the analysis of genotype-phenotype association in next-generation sequencing data. Our group identified a major issue in the analysis of the GAW17 next-generation sequencing data: type I error and ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20650

    authors: Tintle N,Aschard H,Hu I,Nock N,Wang H,Pugh E

    更新日期:2011-01-01 00:00:00

  • Optimized selection of unrelated subjects for whole-genome sequencing studies of rare high-penetrance alleles.

    abstract::Sequencing studies using whole-genome or exome scans are still more expensive than genome-wide association studies on a per-subject basis. As a result, only a subset of subjects from a larger study will be selected for sequencing. To perform an agnostic investigation of the entire genome, subjects may be selected that...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21641

    authors: Edwards TL,Li C

    更新日期:2012-07-01 00:00:00

  • Mantel statistics to correlate gene expression levels from microarrays with clinical covariates.

    abstract::Mantel statistics provide an additional step to standard approaches in the analysis of gene expression and covariate data, allow the calculation of standard statistics such as correlation, partial correlation, and regression coefficients, and, with permutation tests, provide P values for these statistics to relate the...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1115

    authors: Shannon WD,Watson MA,Perry A,Rich K

    更新日期:2002-06-01 00:00:00

  • Data mining and computationally intensive methods: summary of Group 7 contributions to Genetic Analysis Workshop 13.

    abstract::The Framingham Heart Study data, as well as a related simulated data set, were generously provided to the participants of the Genetic Analysis Workshop 13 in order that newly developed and emerging statistical methodologies could be tested on that well-characterized data set. The impetus driving the development of nov...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10285

    authors: Costello TJ,Falk CT,Ye KQ

    更新日期:2003-01-01 00:00:00

  • APO B 3' HVR polymorphism in healthy population: relationships to serum lipid levels.

    abstract::We have analyzed allele frequency distribution at the hypervariable locus 3' to the apolipoprotein B gene in a healthy population sample (241 women and 246 men) from the Belgrade area. The bimodal distribution of sixteen different hypervariable region (HVR) alleles and the heterozygosity index (average 0.76) in both s...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1998)15:2<113::AID-GEPI1>3

    authors: Alavantić D,Glisić S,Kandić I

    更新日期:1998-01-01 00:00:00

  • Random effects model for meta-analysis of multiple quantitative sibpair linkage studies.

    abstract::The growing interest in detection of genetic effects for complex traits along with molecular revolution has stimulated many linkage studies. Multiple replication studies tend to produce different results. In such situations, rigorous meta-analysis methods can be useful for assessing the overall evidence for linkage. W...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1996)13:4<377::AID-GEPI6>3

    authors: Li Z,Rao DC

    更新日期:1996-01-01 00:00:00

  • Autoimmune thyroid disease in type I diabetic families.

    abstract::The prevalence rate for autoimmune thyroid disease (ATD) is about 30 times higher in the type I diabetic (IDDM) families that were ascertained for Genetic Analysis Workshop 5 (GAW5) than in the general population. Two approaches were used to study the clustering of ATD and IDDM in these families: 1) HLA haplotype shar...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370060126

    authors: Payami H,Joe S,Thomson G

    更新日期:1989-01-01 00:00:00

  • GAW10: simulated family data for a common oligogenic disease with quantitative risk factors.

    abstract::GAW10 Problem 2 involves a simulated common disease defined by imposing a threshold, T, on a quantitative trait, Q1. Every individual with a value of Q1 > or = T (where T = 40) is defined as affected. Also thought to be associated with the disease as intervening variables are four other quantitative traits (Q2, Q3, Q4...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1997)14:6<737::AID-GEPI29>

    authors: MacCluer JW,Blangero J,Dyer TD,Speer MC

    更新日期:1997-01-01 00:00:00

  • Tests for gene-environment interaction from case-control data: a novel study of type I error, power and designs.

    abstract::To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non-multiplicative gene-environment effects from case-control studies. In this article, we present a comparative study of four alternative tests for intera...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20337

    authors: Mukherjee B,Ahn J,Gruber SB,Rennert G,Moreno V,Chatterjee N

    更新日期:2008-11-01 00:00:00

  • Evaluation of methods accounting for population structure with pedigree data and continuous outcomes.

    abstract::Methods to account for population structure (PS) in genome-wide association studies have been well developed in samples of unrelated individuals, but when a sample is composed of families, the task of finding and accounting for PS is not as straight forward. Family-based tests that condition on parental genotypes or t...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20590

    authors: Peloso GM,Dupuis J,Lunetta KL

    更新日期:2011-09-01 00:00:00

  • Projection regression models for multivariate imaging phenotype.

    abstract::This paper presents a projection regression model (PRM) to assess the relationship between a multivariate phenotype and a set of covariates, such as a genetic marker, age, and gender. In the existing literature, a standard statistical approach to this problem is to fit a multivariate linear model to the multivariate p...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21658

    authors: Lin JA,Zhu H,Knickmeyer R,Styner M,Gilmore J,Ibrahim JG

    更新日期:2012-09-01 00:00:00

  • Bayesian linkage and segregation analysis: factoring the problem.

    abstract::Complex segregation analysis and linkage methods are mathematical techniques for the genetic dissection of complex diseases. They are used to delineate complex modes of familial transmission and to localize putative disease susceptibility loci to specific chromosomal locations. The computational problem of Bayesian li...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/1098-2272(2000)19:1+<::AID-GEPI8>3.0.CO;2-

    authors: Matthysse S

    更新日期:2000-01-01 00:00:00

  • Design of artificial neural network and its applications to the analysis of alcoholism data.

    abstract::Artificial neural networks were applied to the alcoholism data to reveal nonlinear relationships between intermediate phenotypes, marker identity-by-descent sharing, and the affection status. A variable number of hidden units were considered to achieve a balance between the minimal mean-squared error and over-fitting ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370170738

    authors: Li W,Haghighi F,Falk CT

    更新日期:1999-01-01 00:00:00

  • Genetic epidemiology of cleft lip with or without cleft palate in the population of Hawaii.

    abstract::Orientals consisting of Japanese, Chinese, Koreans, and Filipinos are clearly at higher risk for cleft lip with or without cleft palate [CL(P)] than whites, Puerto Ricans, and Hawaiians/part-Hawaiians in Hawaii. Using the model of diallele cross, CL(P) incidences in incrosses and outcrosses involving 564,002 live birt...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370040603

    authors: Chung CS,Mi MP,Beechert AM

    更新日期:1987-01-01 00:00:00

  • A hybrid design: case-parent triads supplemented by control-mother dyads.

    abstract::Hybrid designs arose from an effort to combine the benefits of family-based and population-based study designs. A recently proposed hybrid approach augments case-parent triads with population-based control-parent triads, genotyping everyone except the control offspring. Including parents of controls substantially impr...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20365

    authors: Vermeulen SH,Shi M,Weinberg CR,Umbach DM

    更新日期:2009-02-01 00:00:00