Truncated tests for combining evidence of summary statistics.

Abstract:

:To date, thousands of genetic variants to be associated with numerous human traits and diseases have been identified by genome-wide association studies (GWASs). The GWASs focus on testing the association between single trait and genetic variants. However, the analysis of multiple traits and single nucleotide polymorphisms (SNPs) might reflect physiological process of complex diseases and the corresponding study is called pleiotropy association analysis. Modern day GWASs report only summary statistics instead of individual-level phenotype and genotype data to avoid logistical and privacy issues. Existing methods for combining multiple phenotypes GWAS summary statistics mainly focus on low-dimensional phenotypes while lose power in high-dimensional cases. To overcome this defect, we propose two kinds of truncated tests to combine multiple phenotypes summary statistics. Extensive simulations show that the proposed methods are robust and powerful when the dimension of the phenotypes is high and only part of the phenotypes are associated with the SNPs. We apply the proposed methods to blood cytokines data collected from Finnish population. Results show that the proposed tests can identify additional genetic markers that are missed by single trait analysis.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Bu D,Yang Q,Meng Z,Zhang S,Li Q

doi

10.1002/gepi.22330

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

687-701

issue

7

eissn

0741-0395

issn

1098-2272

journal_volume

44

pub_type

杂志文章
  • Apolipoprotein E-epsilon 4 allele and familial risk in Alzheimer's disease.

    abstract::Recent studies have found an association between presence of apolipoprotein E (APOE) epsilon 4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the epsilon 4 allele with the relatives of A...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1996)13:3<285::AID-GEPI5>3

    authors: Li G,Silverman JM,Altstiel LD,Haroutunian V,Perl DP,Purohit D,Birstein S,Lantz M,Mohs RC,Davis KL

    更新日期:1996-01-01 00:00:00

  • Pleiotropy and principal components of heritability combine to increase power for association analysis.

    abstract::When many correlated traits are measured the potential exists to discover the coordinated control of these traits via genotyped polymorphisms. A common statistical approach to this problem involves assessing the relationship between each phenotype and each single nucleotide polymorphism (SNP) individually (PHN); and t...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20257

    authors: Klei L,Luca D,Devlin B,Roeder K

    更新日期:2008-01-01 00:00:00

  • Analysis of two-locus traits under heterogeneity for recessive versus dominant inheritance.

    abstract::Complex traits have been modeled under various modes of two-locus inheritance. One example of a two-locus threshold model is the situation where an individual is susceptible to a disease trait if he or she carries three or more disease alleles. Under this model, if each locus is examined individually the inheritance a...

    journal_title:Genetic epidemiology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/(SICI)1098-2272(1997)14:6<1097::AID-GEPI89

    authors: Leal SM,Ott J

    更新日期:1997-01-01 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

  • Linkage analysis of asthma and atopy including models with genomic imprinting.

    abstract::Asthma and atopy are two closely related, common complex traits in which a number of genetic and environmental factors are suspected to play a role. We have performed parametric and nonparametric multi-marker linkage analysis for the Busselton data set, which is part of problem 1 of Genetic Analysis Workshop 12. In pa...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s204

    authors: Strauch K,Bogdanow M,Fimmers R,Baur MP,Wienker TF

    更新日期:2001-01-01 00:00:00

  • SNP selection in genome-wide and candidate gene studies via penalized logistic regression.

    abstract::Penalized regression methods offer an attractive alternative to single marker testing in genetic association analysis. Penalized regression methods shrink down to zero the coefficient of markers that have little apparent effect on the trait of interest, resulting in a parsimonious subset of what we hope are true perti...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20543

    authors: Ayers KL,Cordell HJ

    更新日期:2010-12-01 00:00:00

  • Efficient strategy for detecting gene × gene joint action and its application in schizophrenia.

    abstract::We propose a new approach to detect gene × gene joint action in genome-wide association studies (GWASs) for case-control designs. This approach offers an exhaustive search for all two-way joint action (including, as a special case, single gene action) that is computationally feasible at the genome-wide level and has r...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21779

    authors: Won S,Kwon MS,Mattheisen M,Park S,Park C,Kihara D,Cichon S,Ophoff R,Nöthen MM,Rietschel M,Baur M,Uitterlinden AG,Hofmann A,GROUP Investigators.,Lange C

    更新日期:2014-01-01 00:00:00

  • Multivariate genetic analysis of apo AI concentration and HDL subfractions: evidence for major locus pleiotropy.

    abstract::A major locus influencing apolipoprotein AI (apo AI) serum levels was detected using data from the Donner Laboratory Family Study. This locus accounts for 46% of the phenotypic variability in apo AI levels. Multivariate segregation analysis revealed that this major locus also has significant pleiotropic effects on the...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370100648

    authors: Blangero J,Williams-Blangero S,Mahaney MC

    更新日期:1993-01-01 00:00:00

  • Robust inference for variance components models in families ascertained through probands: I. Conditioning on proband's phenotype.

    abstract::A robust approach for estimating standard errors of variance components by using quantitative phenotypes from families ascertained through a proband with an extreme phenotypic value is presented. Estimators that use the multivariate normal distribution as a "working likelihood" are obtained by computing conditional ln...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370040305

    authors: Beaty TH,Liang KY

    更新日期:1987-01-01 00:00:00

  • Regionally Smoothed Meta-Analysis Methods for GWAS Datasets.

    abstract::Genome-wide association studies are proven tools for finding disease genes, but it is often necessary to combine many cohorts into a meta-analysis to detect statistically significant genetic effects. Often the component studies are performed by different investigators on different populations, using different chips wi...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21949

    authors: Begum F,Sharker MH,Sherman SL,Tseng GC,Feingold E

    更新日期:2016-02-01 00:00:00

  • Linkage disequilibrium between DNA markers at the low-density lipoprotein receptor gene.

    abstract::We determined pairwise linkage disequilibria between 12 restriction fragment length polymorphism (RFLP) markers at or near the low-density lipoprotein receptor (LDLR) locus on chromosome 19p13.2-13.1 in 92 unrelated individuals. Of these 12 RFLPs, two were newly identified under a cosmid-based strategy designed to scr...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070114

    authors: Hegele RA,Plaetke R,Lalouel JM

    更新日期:1990-01-01 00:00:00

  • The insulin gene and susceptibility to IDDM.

    abstract::The association between insulin-dependent diabetes mellitus (IDDM) and an allele of a restriction fragment length polymorphism (RFLP) 5' to the coding region of the insulin gene has raised the possibility that variation in the vicinity of the insulin gene confers susceptibility to IDDM. To test this hypothesis, the di...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370060113

    authors: Cox NJ,Spielman RS

    更新日期:1989-01-01 00:00:00

  • Haplotype kernel association test as a powerful method to identify chromosomal regions harboring uncommon causal variants.

    abstract::For most complex diseases, the fraction of heritability that can be explained by the variants discovered from genome-wide association studies is minor. Although the so-called "rare variants" (minor allele frequency [MAF] < 1%) have attracted increasing attention, they are unlikely to account for much of the "missing h...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21740

    authors: Lin WY,Yi N,Lou XY,Zhi D,Zhang K,Gao G,Tiwari HK,Liu N

    更新日期:2013-09-01 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

  • Multifactorial disease risk calculator: Risk prediction for multifactorial disease pedigrees.

    abstract::Construction of multifactorial disease models from epidemiological findings and their application to disease pedigrees for risk prediction is nontrivial for all but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool facilitating this. It provides a user-friendly interface, extending a reported...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22101

    authors: Campbell DD,Li Y,Sham PC

    更新日期:2018-03-01 00:00:00

  • Modeling the HLA component in rheumatoid arthritis: sensitivity to DRB1 allele frequencies.

    abstract::Rheumatoid arthritis is an inflammatory disease for which positive associations have been described with some HLA-DRB1 alleles. The associated alleles share a similar amino acid sequence in the third hypervariable region, the shared epitope, but differ at position 71 and 86. It has been suggested that HLA susceptibili...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/1098-2272(200012)19:4<422::AID-GEPI12>3.0.

    authors: Tézenas du Montcel S,Reviron D,Genin E,Roudier J,Mercier P,Clerget-Darpoux F

    更新日期:2000-12-01 00:00:00

  • Major genetic effects on airway-parenchymal dysanapsis of the lung: the Humboldt family study.

    abstract::We examined familial resemblance and performed segregation analysis for the maximal expiratory flow rate at 50% of vital capacity (Vmax50) and the ratio of Vmax50 to forced vital capacity (FVC), based on data from 309 nuclear families with 1,045 individuals in the town of Humboldt, Saskatchewan, in 1993. Vmax50 is con...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1999)16:1<95::AID-GEPI8>3.

    authors: Chen Y,Dosman JA,Rennie DC,Lockinger LA

    更新日期:1999-01-01 00:00:00

  • Progress toward resolving the possible linkage of multiple endocrine neoplasia type 2A to haptoglobin and group-specific loci: use of restriction fragment length polymorphisms extends exclusion region.

    abstract::In an earlier paper, positive but nonsignificant lod scores were found in pair-wise linkage tests between multiple endocrine neoplasia type 2A (MEN-2A) and both the haptoglobin (HP) locus on chromosome 16 and group-specific component (GC) locus on chromosome 4. Recently discovered restriction fragment length polymorph...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370030306

    authors: Kidd KK,Kidd JR,Castiglione CM,Pakstis AJ,Sparkes RS

    更新日期:1986-01-01 00:00:00

  • Scope and strategies of genetic epidemiology: analysis of articles published in Genetic Epidemiology, 1984-1991.

    abstract::Genetic epidemiology is a relatively new discipline that seeks to unravel the role of genetic factors and their interactions with environmental factors in the etiology of diseases, using population and family study approaches. To characterize the overall direction and emphasis of research strategies used in this field...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370100505

    authors: Khoury MJ,Beaty TH,Cohen BH

    更新日期:1993-01-01 00:00:00

  • Familial analysis of eosinophilia caused by helminthic parasites.

    abstract::A highly significant familial aggregation of eosinophil levels (X2(3) = 38.00) was detected in a sample from three Brazilian populations with a high incidence of helminthic parasitism. The data were unable to resolve genetic or common environment causation due to the lack of environmental concomitant variables. Result...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370090305

    authors: Moro-Furlani AM,Krieger H

    更新日期:1992-01-01 00:00:00

  • Parental transmission and D18S37 allele sharing in bipolar affective disorder.

    abstract::We combined the five chromosome 18 bipolar affective disorder data sets provided by GAW10, totaling 185 families with 3,394 individuals, and performed analysis of differential parental transmission and chromosome 18 marker allele sharing in families with transmission through fathers vs those through mothers. Results i...

    journal_title:Genetic epidemiology

    pub_type: 临床试验,杂志文章

    doi:10.1002/(SICI)1098-2272(1997)14:6<665::AID-GEPI19>

    authors: Lin JP,Bale SJ

    更新日期:1997-01-01 00:00:00

  • Haplotype sharing analysis in affected individuals from nuclear families with at least one affected offspring.

    abstract::In diseases with a complex mode of inheritance, families with multiple affected individuals are difficult to ascertain. The haplotype sharing statistic (HSS) uses (hidden) co-ancestry between affected individuals from a founder population. These affected individuals will likely not only share the same mutation(s), but...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1997)14:6<915::AID-GEPI59>

    authors: Van der Meulen MA,te Meerman GJ

    更新日期:1997-01-01 00:00:00

  • Use of variable marker density, principal components, and neural networks in the dissection of disease etiology.

    abstract::Several approaches were taken to identify the loci contributing to the quantitative and qualitative phenotypes in the Genetic Analysis Workshop 12 simulated data set. To identify possible quantitative trait loci (QTL), the quantitative traits were analyzed using SOLAR. The four replicates identified as the "best repli...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s732

    authors: Pankratz N,Kirkwood SC,Flury L,Koller DL,Foroud T

    更新日期:2001-01-01 00:00:00

  • Sib-pair linkage tests for disease susceptibility loci: common tests vs. the asymptotically most powerful test.

    abstract::Several statistical tests for linkage between a disease susceptibility locus and a marker locus for sib-pair data are examined analytically. Two common statistics, a test based on the mean number of marker alleles shared identical by descent by sib-pairs, and a test based on the proportion of sib-pairs sharing exactly...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070506

    authors: Schaid DJ,Nick TG

    更新日期:1990-01-01 00:00:00

  • Bayesian meta-analysis across genome-wide association studies of diverse phenotypes.

    abstract::Genome-wide association studies (GWAS) are a powerful tool for understanding the genetic basis of diseases and traits, but most studies have been conducted in isolation, with a focus on either a single or a set of closely related phenotypes. We describe MetABF, a simple Bayesian framework for performing integrative me...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章,meta分析

    doi:10.1002/gepi.22202

    authors: Trochet H,Pirinen M,Band G,Jostins L,McVean G,Spencer CCA

    更新日期:2019-07-01 00:00:00

  • Analysis of multiple phenotypes.

    abstract::The complex etiology of common diseases like cardiovascular disease, diabetes, hypertension, and rheumatoid arthritis has led investigators to focus on the genetics of correlated phenotypes and risk factors. Joint analysis of multiple disease-related phenotypes may reveal genes of pleiotropic effect and increase analy...

    journal_title:Genetic epidemiology

    pub_type:

    doi:10.1002/gepi.20470

    authors: Kent JW Jr

    更新日期:2009-01-01 00:00:00

  • Genetic association tests based on ranks (GATOR) for quantitative traits with and without censoring.

    abstract::Linkage disequilibrium mapping of quantitative traits is a powerful method for dissecting the genetic etiology of complex phenotypes. Quantitative traits, however, often exhibit characteristics that make their use problematic. For example, the distribution of the trait may be censored, highly skewed, or contaminated w...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20141

    authors: Allen AS,Martin ER,Qin X,Li YJ

    更新日期:2006-04-01 00:00:00

  • Sequencing and imputation in GWAS: Cost-effective strategies to increase power and genomic coverage across diverse populations.

    abstract::A key aim for current genome-wide association studies (GWAS) is to interrogate the full spectrum of genetic variation underlying human traits, including rare variants, across populations. Deep whole-genome sequencing is the gold standard to fully capture genetic variation, but remains prohibitively expensive for large...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22326

    authors: Quick C,Anugu P,Musani S,Weiss ST,Burchard EG,White MJ,Keys KL,Cucca F,Sidore C,Boehnke M,Fuchsberger C

    更新日期:2020-09-01 00:00:00

  • Parental genotype reconstruction: applications of haplotype relative risk to incomplete parental data.

    abstract::Intended to resolve the problem of constructing a matched population-based control sample, haplotype relative risk techniques frequently suffer from loss of power for late-onset diseases due to unavailability of parental genotypes that are required to form parent-offspring pairs. However, much of this missing informat...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1998)15:5<471::AID-GEPI3>3

    authors: Martin RB,Alda M,MacLean CJ

    更新日期:1998-01-01 00:00:00

  • Power of non-parametric linkage analysis in mapping genes contributing to human longevity in long-lived sib-pairs.

    abstract::This report investigates the power issue in applying the non-parametric linkage analysis of affected sib-pairs (ASP) [Kruglyak and Lander, 1995: Am J Hum Genet 57:439-454] to localize genes that contribute to human longevity using long-lived sib-pairs. Data were simulated by introducing a recently developed statistica...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10304

    authors: Tan Q,Zhao JH,Iachine I,Hjelmborg J,Vach W,Vaupel JW,Christensen K,Kruse TA

    更新日期:2004-04-01 00:00:00