Advertisement

Topics

Trans-ethnic predicted expression genome-wide association analysis identifies a gene for estrogen receptor-negative breast cancer.

08:00 EDT 28th September 2017 | BioPortfolio

Summary of "Trans-ethnic predicted expression genome-wide association analysis identifies a gene for estrogen receptor-negative breast cancer."

Genome-wide association studies (GWAS) have identified more than 90 susceptibility loci for breast cancer, but the underlying biology of those associations needs to be further elucidated. More genetic factors for breast cancer are yet to be identified but sample size constraints preclude the identification of individual genetic variants with weak effects using traditional GWAS methods. To address this challenge, we utilized a gene-level expression-based method, implemented in the MetaXcan software, to predict gene expression levels for 11,536 genes using expression quantitative trait loci and examine the genetically-predicted expression of specific genes for association with overall breast cancer risk and estrogen receptor (ER)-negative breast cancer risk. Using GWAS datasets from a Challenge launched by National Cancer Institute, we identified TP53INP2 (tumor protein p53-inducible nuclear protein 2) at 20q11.22 to be significantly associated with ER-negative breast cancer (Z = -5.013, p = 5.35×10-7, Bonferroni threshold = 4.33×10-6). The association was consistent across four GWAS datasets, representing European, African and Asian ancestry populations. There are 6 single nucleotide polymorphisms (SNPs) included in the prediction of TP53INP2 expression and five of them were associated with estrogen-receptor negative breast cancer, although none of the SNP-level associations reached genome-wide significance. We conducted a replication study using a dataset outside of the Challenge, and found the association between TP53INP2 and ER-negative breast cancer was significant (p = 5.07x10-3). Expression of HP (16q22.2) showed a suggestive association with ER-negative breast cancer in the discovery phase (Z = 4.30, p = 1.70x10-5) although the association was not significant after Bonferroni adjustment. Of the 249 genes that are 250 kb within known breast cancer susceptibility loci identified from previous GWAS, 20 genes (8.0%) were statistically significant associated with ER-negative breast cancer (p<0.05), compared to 582 (5.2%) of 11,287 genes that are not close to previous GWAS loci. This study demonstrated that expression-based gene mapping is a promising approach for identifying cancer susceptibility genes.

Affiliation

Journal Details

This article was published in the following journal.

Name: PLoS genetics
ISSN: 1553-7404
Pages: e1006727

Links

DeepDyve research library

PubMed Articles [41175 Associated PubMed Articles listed on BioPortfolio]

Immunochip meta-analysis of inflammatory bowel disease identifies three novel loci and four novel associations in previously reported loci.

Recent meta-analysis of genome-wide association studies have identified over 241 inflammatory bowel disease susceptibility loci. However, the known variants only account for a fraction of inflammatory...

Analyses of genome wide association data, cytokines, and gene expression in African-Americans with benign ethnic neutropenia.

Benign ethnic neutropenia (BEN) is a hematologic condition associated with people of African ancestry and specific Middle Eastern ethnic groups. Prior genetic association studies in large population s...

Genome wide identification and predicted functional analyses of NAC transcription factors in Asian pears.

NAC proteins contribute to diverse plant developmental processes as well as tolerances to biotic and abiotic stresses. The pear genome had been decoded and provided the basis for the genome-wide analy...

The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) Study: A trans-ethnic meta-analysis.

Current knowledge of the genetic architecture of key reproductive events across the female life course is largely based on association studies of European descent women. The relevance of known loci fo...

The role of CDKN2B in cardiovascular risk in ethnic Saudi Arabs: A validation study.

Genome-wide association studies (GWASs) have yielded a wealth of information furnishing support for the variability in genetic predisposition to disease. However, the actual impact of such findings on...

Clinical Trials [6420 Associated Clinical Trials listed on BioPortfolio]

Genome-Wide Association Study in Patients With Nontuberculous Mycobacterial Lung Disease

The aim of this study was to elucidate genetic susceptibility of patients with nontuberculous mycobacterial lung disease using genome-wide association study.

PheWAS of a Polygenic Predictor of Thyroid Function

Performing a phenome-wide association study (PheWAS) identifying clinical diagnoses associated with a polygenic predictor of Thyroid stimulating hormone (TSH) levels identified by a previo...

Identification of Genetic Polymorphism Related to Acute Kidney Injury After Liver Transplantation Through Genome-wide Association Study (GWAS) in Korean Population

Some of the liver transplantation recipients experience postoperative acute kidney injury due to various causes including genetic factors. Prevention of postoperative acute kidney injury i...

Study of the Molecular Genetics of Menstrual Migraine

The investigators hypothesize that genes that play a role in menstrual migraine can be identified using a well characterised migraine population and a comprehensive genome-wide association...

Enhanced Linkage Maps From Family-Based Genetics Studies

To develop genetic maps for the genome-wide screening markers used by multiple investigators and to investigate map differences between sexes and different ethnic groups.

Medical and Biotech [MESH] Definitions

An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.

A coordinated effort of researchers to map (CHROMOSOME MAPPING) and sequence (SEQUENCE ANALYSIS, DNA) the human GENOME.

Trans-acting transcription factors produced by retroviruses such as HIV. They are nuclear proteins whose expression is required for viral replication. The tat protein stimulates LONG TERMINAL REPEAT-driven RNA synthesis for both viral regulatory and viral structural proteins. tat stands for trans-activation of transcription.

Expulsion of a population from a given territory due to religious or ethnic discrimination, political, strategic or ideological considerations, or a combination of these.

A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Breast Cancer
Track and monitor developments in breast cancer research and commercial development.  Follow the tabs above to read the latest global news, research, clinical trials on breast cancer and follow companies active in the development of breast cancer tr...


Searches Linking to this Article