Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.

Abstract:

:Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Feng H,Gusev A,Pasaniuc B,Wu L,Long J,Abu-Full Z,Aittomäki K,Andrulis IL,Anton-Culver H,Antoniou AC,Arason A,Arndt V,Aronson KJ,Arun BK,Asseryanis E,Auer PL,Azzollini J,Balmaña J,Barkardottir RB,Barnes DR,Barrowda

doi

10.1002/gepi.22288

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

442-468

issue

5

eissn

0741-0395

issn

1098-2272

journal_volume

44

pub_type

杂志文章
  • Risk factors for atherosclerosis in twins.

    abstract::We performed multivariate genetic analyses of cardiovascular risk factors from two sets of data on US and Australian female twins. Similar models for body mass index (BMI), serum low density (LDL) and high density (HDL) lipoproteins, including age as a covariate, were fitted successfully to both groups. These suggeste...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370100638

    authors: Duffy DL,O'Connell DL,Heller RF,Martin NG

    更新日期:1993-01-01 00:00:00

  • Comparison of two linkage inference procedures for genes related to the P300 component of the event related potential.

    abstract::Our goal was to detect genes contributing to the P300 component of the event related potential (ERP). We found that all of the ERP traits were highly correlated. Most of them distinguished alcoholics from nonalcoholics. To have one summary variable for the ERP traits, we calculated the first principal component (PRIN1...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370170728

    authors: Goldin LR,Chase GA

    更新日期:1999-01-01 00:00:00

  • Meta-Analysis of Rare Variant Association Tests in Multiethnic Populations.

    abstract::Several methods have been proposed to increase power in rare variant association testing by aggregating information from individual rare variants (MAF < 0.005). However, how to best combine rare variants across multiple ethnicities and the relative performance of designs using different ethnic sampling fractions remai...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21939

    authors: Mensah-Ablorh A,Lindstrom S,Haiman CA,Henderson BE,Marchand LL,Lee S,Stram DO,Eliassen AH,Price A,Kraft P

    更新日期:2016-01-01 00:00:00

  • Estimating gene penetrance from family data.

    abstract::Family data are useful for estimating disease risk in carriers of specific genotypes of a given gene (penetrance). Penetrance is frequently estimated assuming that relatives' phenotypes are independent, given their genotypes for the gene of interest. This assumption is unrealistic when multiple shared risk factors con...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20493

    authors: Gong G,Hannon N,Whittemore AS

    更新日期:2010-05-01 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

  • Genome-wide family-based linkage analysis of exome chip variants and cardiometabolic risk.

    abstract::Linkage analysis of complex traits has had limited success in identifying trait-influencing loci. Recently, coding variants have been implicated as the basis for some biomedical associations. We tested whether coding variants are the basis for linkage peaks of complex traits in 42 African-American (n = 596) and 90 His...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21801

    authors: Hellwege JN,Palmer ND,Raffield LM,Ng MC,Hawkins GA,Long J,Lorenzo C,Norris JM,Ida Chen YD,Speliotes EK,Rotter JI,Langefeld CD,Wagenknecht LE,Bowden DW

    更新日期:2014-05-01 00:00:00

  • Genetic analysis of a complex disease in the presence of an environmental risk factor.

    abstract::The role of a gene in a disease may be hidden by the presence of another risk factor such as an environmental factor. In that case, stratifying the data according to this factor strengthens power to detect linkage or association. We followed this strategy on the simulated data provided by GAW11. The transmission/diseq...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370170788

    authors: Eichenbaum-Voline S,Baur MP,Knapp M

    更新日期:1999-01-01 00:00:00

  • Power and sample size calculations for SNP association studies with censored time-to-event outcomes.

    abstract::For many clinical studies in cancer, germline DNA is prospectively collected for the purpose of discovering or validating single-nucleotide polymorphisms (SNPs) associated with clinical outcomes. The primary clinical endpoint for many of these studies are time-to-event outcomes such as time of death or disease progres...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21645

    authors: Owzar K,Li Z,Cox N,Jung SH

    更新日期:2012-09-01 00:00:00

  • Deciphering Genome Environment Wide Interactions Using Exposed Subjects Only.

    abstract::The recent successes of genome-wide association studies (GWAS) have renewed interest in genome environment wide interaction studies (GEWIS) to discover genetic factors that modulate penetrance of environmental exposures to human diseases. Indeed, gene-environment interactions (G × E), which have not been emphasized in...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21890

    authors: Zhao LP,Fan W,Goodman G,Radich J,Martin P

    更新日期:2015-07-01 00:00:00

  • Extensions to sib-pair linkage tests applicable to disorders characterized by delayed onset.

    abstract::Extensions of the approach to sib-pair linkage tests developed by Haseman and Elston [Behav Genet 2:3-19, 1972] are proposed which incorporate information on age of onset and age at examination. Alternate sources for the age of onset corrections are described, including models for the estimation of parameters associat...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070607

    authors: Dawson DV,Kaplan EB,Elston RC

    更新日期:1990-01-01 00:00:00

  • Innovative approach to identify multigenomic and environmental interactions associated with birth defects in family-based hybrid designs.

    abstract::Genes, including those with transgenerational effects, work in concert with behavioral, environmental, and social factors via complex biological networks to determine human health. Understanding complex relationships between causal factors underlying human health is an essential step towards deciphering biological mec...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22363

    authors: Lou XY,Hou TT,Liu SY,Xu HM,Lin F,Tang X,MacLeod SL,Cleves MA,Hobbs CA

    更新日期:2020-09-30 00:00:00

  • Genetic heterogeneity in Alzheimer's disease: a grade of membership analysis.

    abstract::Grade of membership analysis (GoM) may have particular relevance for genetic epidemiology. The method can flexibly relate genetic markers, clinical features, and environmental exposures to possible subtypes of disease termed pure types even when population allele frequencies and penetrance functions are not known. Hen...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370100628

    authors: Corder EH,Woodbury MA

    更新日期:1993-01-01 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

  • Score tests for familial correlation in genotyped-proband designs.

    abstract::In the genotyped-proband design, a proband is selected based on an observed phenotype, the genotype of the proband is observed, and then the phenotypes of all first-degree relatives are obtained. The genotypes of these first-degree relatives are not observed. Gail et al. [(1999) Genet Epidemiol] discuss likelihood ana...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(200004)18:4<293::AID-GEPI3

    authors: Carroll RJ,Gail MH,Benichou J,Pee D

    更新日期:2000-04-01 00:00:00

  • Modelling the major histocompatibility complex susceptibility to RA using the MASC method.

    abstract::To explain the association between HLA-DRB1 gene and rheumatoid arthritis (RA), two main hypotheses have been proposed. The first, the shared epitope hypothesis, assumes a direct role of DRB1 in RA susceptibility. The second hypothesis assumes a recessive disease susceptibility gene in linkage disequilibrium with DRB1...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1998)15:4<419::AID-GEPI7>3

    authors: Génin E,Babron MC,McDermott MF,Mulcahy B,Waldron-Lynch F,Adams C,Clegg DO,Ward RH,Shanahan F,Molloy MG,O'Gara F,Clerget-Darpoux F

    更新日期:1998-01-01 00:00:00

  • Comparison of the QTDT analysis for IgE in the CSGA data set.

    abstract::Over the past few years at least 13 transmission/disequilibrium test (TDT)-based tests have been developed for quantitative (Q) traits for the assessment of association or linkage in the presence of the other. A total of six of these QTDT methods were used to analyze log10IgE in the Collaborative Study on the Genetics...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s312

    authors: Page GP,Wilcox MA,Occhiuto J,Adak S,Neuberg D,Bajorunaite R,George V

    更新日期:2001-01-01 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

  • Conditional multipoint linkage analysis using affected sib pairs: an alternative approach.

    abstract::Recently, Liang et al. ([2001b] Genet. Epidemiol. 21:105-122) proposed a conditional approach to assess linkage evidence on the target region by incorporating linkage information from an unlinked (reference) region using allele shared IBD (identity-by-decent) from affected sib pairs. This is carried out by conditionin...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10305

    authors: Chiu YF,Liang KY

    更新日期:2004-02-01 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

  • Presidential address: Six open questions to genetic epidemiologists.

    abstract::Given the rapid pace with which genomics and other -omics disciplines are evolving, it is sometimes necessary to shift down a gear to consider more general scientific questions. In this line, in my presidential address I formulate six questions for genetic epidemiologists to ponder on. These cover the areas of reprodu...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22191

    authors: König IR

    更新日期:2019-04-01 00:00:00

  • A sliding-window weighted linkage disequilibrium test.

    abstract::Multilocus linkage disequilibrium (LD) tests that consider inter-marker (LD) are more powerful than single-locus tests when disease etiology is contributed simultaneously by several linked and correlated loci. However, inclusion of redundant non-informative markers may result in reduced testing power and/or inflated f...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20165

    authors: Yang HC,Lin CY,Fann CS

    更新日期:2006-09-01 00:00:00

  • Biochemical intermediates in alpha 1-antitrypsin deficiency: residual family resemblance for total alpha 1-antitrypsin, oxidized alpha 1-antitrypsin, and immunoglobulin E after adjustment for the effect of the Pi locus.

    abstract::alpha 1-antitrypsin (alpha 1 AT) deficiency is variably associated with the development of pulmonary emphysema. To gain insight into the process which begins the Z point mutation at the Protease Inhibitor (Pi) locus and results in the variable development of emphysema, three quantitative phenotypes, including total al...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070204

    authors: Silverman EK,Province MA,Campbell EJ,Pierce JA,Rao DC

    更新日期:1990-01-01 00:00:00

  • Segregation analysis of autosomal dominant polycystic kidney disease.

    abstract::The results of classical segregation analysis on 159 families with polycystic kidney disease (PKD) are presented. It had been previously estimated that about 95% of autosomal dominant PKD (ADPKD) families have PKD1, the gene localized to chromosome 16p. The main purpose of the study was to determine if PKD shows any s...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370100305

    authors: Dobin A,Kimberling WJ,Pettinger W,Bailey-Wilson JE,Shugart YY,Gabow P

    更新日期:1993-01-01 00:00:00

  • Functional-mixed effects models for candidate genetic mapping in imaging genetic studies.

    abstract::The aim of this paper is to develop a functional-mixed effects modeling (FMEM) framework for the joint analysis of high-dimensional imaging data in a large number of locations (called voxels) of a three-dimensional volume with a set of genetic markers and clinical covariates. Our FMEM is extremely useful for efficient...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21854

    authors: Lin JA,Zhu H,Mihye A,Sun W,Ibrahim JG,Alzheimer's Neuroimaging Initiative.

    更新日期:2014-12-01 00:00:00

  • Association mapping, using a mixture model for complex traits.

    abstract::Association mapping for complex diseases using unrelated individuals can be more powerful than family-based analysis in many settings. In addition, this approach has major practical advantages, including greater efficiency in sample recruitment. Association mapping may lead to false-positive findings, however, if popu...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.210

    authors: Zhu X,Zhang S,Zhao H,Cooper RS

    更新日期:2002-08-01 00:00:00

  • A flexible and parallelizable approach to genome-wide polygenic risk scores.

    abstract::The heritability of most complex traits is driven by variants throughout the genome. Consequently, polygenic risk scores, which combine information on multiple variants genome-wide, have demonstrated improved accuracy in genetic risk prediction. We present a new two-step approach to constructing genome-wide polygenic ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22245

    authors: Newcombe PJ,Nelson CP,Samani NJ,Dudbridge F

    更新日期:2019-10-01 00:00:00

  • Regressive logistic modeling of familial aggregation for asthma in 7,394 population-based nuclear families.

    abstract::The aim of this population-based study was to determine whether asthma aggregates in families, and if so, whether aggregation was consistent with environmental and/or genetic etiologies. Data were from 7,394 nuclear families (41,506 individuals) from the 1968 Tasmanian Asthma Survey, in which all Tasmanian schoolchild...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1997)14:3<317::AID-GEPI9>3

    authors: Jenkins MA,Hopper JL,Giles GG

    更新日期:1997-01-01 00:00:00

  • Information on ancestry from genetic markers.

    abstract::It is possible to estimate the proportionate contributions of ancestral populations to admixed individuals or populations using genetic markers, but different loci and alleles vary considerably in the amount of information that they provide. Conventionally, the allele frequency difference between parental populations ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10319

    authors: Pfaff CL,Barnholtz-Sloan J,Wagner JK,Long JC

    更新日期:2004-05-01 00:00:00

  • On the association analysis of genome-sequencing data: A spatial clustering approach for partitioning the entire genome into nonoverlapping windows.

    abstract::For the association analysis of whole-genome sequencing (WGS) studies, we propose an efficient and fast spatial-clustering algorithm. Compared to existing analysis approaches for WGS data, that define the tested regions either by sliding or consecutive windows of fixed sizes along variants, a meaningful grouping of ne...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22040

    authors: Loehlein Fier H,Prokopenko D,Hecker J,Cho MH,Silverman EK,Weiss ST,Tanzi RE,Lange C

    更新日期:2017-05-01 00:00:00

  • A small-sample multivariate kernel machine test for microbiome association studies.

    abstract::High-throughput sequencing technologies have enabled large-scale studies of the role of the human microbiome in health conditions and diseases. Microbial community level association test, as a critical step to establish the connection between overall microbiome composition and an outcome of interest, has now been rout...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22030

    authors: Zhan X,Tong X,Zhao N,Maity A,Wu MC,Chen J

    更新日期:2017-04-01 00:00:00