scholarly journals A genome-wide association study of mitochondrial DNA copy number in two population-based cohorts

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Anna L. Guyatt ◽  
Rebecca R. Brennan ◽  
Kimberley Burrows ◽  
Philip A. I. Guthrie ◽  
Raimondo Ascione ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Association Study ◽  
Copy Number ◽  
Genome Wide Association Study ◽  
Population Based ◽  
Genome Wide Association ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Genome Wide ◽  
A Genome

scholarly journals A genome-wide association study of mitochondrial DNA copy number in two population-based cohorts

2018 ◽  
Author(s):  
Anna L. Guyatt ◽  
Rebecca R. Brennan ◽  
Kimberley Burrows ◽  
Philip A. I. Guthrie ◽  
Raimondo Ascione ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Genome Wide ◽  
A Genome

AbstractMitochondrial DNA copy number (mtDNA CN) exhibits interindividual and intercellular variation, but few genome-wide association studies (GWAS) of directly assayed mtDNA CN exist.We undertook a GWAS of qPCR-assayed mtDNA CN in the Avon Longitudinal Study of Parents and Children (ALSPAC), and the UK Blood Service (UKBS) cohort. After validating and harmonising data, 5461 ALSPAC mothers (16-43 years at mtDNA CN assay), and 1338 UKBS females (17-69 years) were included in a meta-analysis. Sensitivity analyses restricted to females with white cell-extracted DNA, and adjusted for estimated or assayed cell proportions. Associations were also explored in ALSPAC children, and UKBS males.A neutrophil-associated locus approached genome-wide significance (rs709591 [MED24], β[SE] −0.084 [0.016], p=1.54e-07) in the main meta-analysis of adult females. This association was concordant in magnitude and direction in UKBS males and ALSPAC neonates. SNPs in and around ABHD8 were associated with mtDNA CN in ALSPAC neonates (rs10424198, β[SE] 0.262 [0.034], p=1.40e-14), but not other study groups. In a meta-analysis of unrelated individuals (N=11253), we replicated a published association in TFAM β[SE] 0.046 [0.017], p=0.006), with an effect size much smaller than that observed in the replication analysis of a previous in silico GWAS.In a hypothesis-generating GWAS, we confirm an association between TFAM and mtDNA CN, and present putative loci requiring replication in much larger samples. We discuss the limitations of our work, in terms of measurement error and cellular heterogeneity, and highlight the need for larger studies to better understand nuclear genomic control of mtDNA copy number.

scholarly journals A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0163048 ◽  
Author(s):  
Silvia Alemany ◽  
Natàlia Vilor-Tejedor ◽  
Mariona Bustamante ◽  
Jesús Pujol ◽  
Dídac Macià ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Population Based ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Attention Function

scholarly journals A Genome-Wide Association Study to Identify Potential Germline Copy Number Variants for Sporadic Breast Cancer Susceptibility

2016 ◽  
Vol 149 (3) ◽  
pp. 156-164 ◽  
Author(s):  
Yadav Sapkota ◽  
Ashok Narasimhan ◽  
Mahalakshmi Kumaran ◽  
Badan S. Sehrawat ◽  
Sambasivarao Damaraju
Keyword(s):  
Breast Cancer ◽  
Association Study ◽  
Copy Number ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Frequency Effect ◽  
Potential Candidate ◽  
Disease Etiology ◽  
Genome Wide ◽  
A Genome

Breast cancer (BC) predisposition in populations arises from both genetic and nongenetic risk factors. Structural variations such as copy number variations (CNVs) are heritable determinants for disease susceptibility. The primary objectives of this study are (1) to identify CNVs associated with sporadic BC using a genome-wide association study (GWAS) design; (2) to utilize 2 distinct CNV calling algorithms to identify concordant CNVs as a strategy to reduce false positive associations in the hypothesis-generating GWAS discovery phase, and (3) to identify potential candidate CNVs for follow-up replication studies. We used Affymetrix SNP Array 6.0 data profiled on Caucasian subjects (422 cases/348 controls) to call CNVs using algorithms implemented in Nexus Copy Number and Partek Genomics Suite software. Nexus algorithm identified CNVs associated with BC (731 autosomal CNVs with >5% frequency in the total sample and Q < 0.05). Thirteen CNVs were identified when Partek algorithm-called CNVs were overlapped with Nexus-identified CNVs; these CNVs showed concordances for frequency, effect size, and direction. Coding genes present within BC-associated CNVs were known to play a role in disease etiology and prognosis. Long noncoding RNAs identified within CNVs showed tissue-specific expression, indicating potential functional relevance of the findings. The identified candidate CNVs warrant independent replication.

A genome-wide association study of copy number variations with umbilical hernia in swine

2016 ◽  
Vol 47 (3) ◽  
pp. 298-305 ◽  
Author(s):  
Yi Long ◽  
Ying Su ◽  
Huashui Ai ◽  
Zhiyan Zhang ◽  
Bin Yang ◽  
...  
Keyword(s):  
Association Study ◽  
Copy Number ◽  
Umbilical Hernia ◽  
Genome Wide Association Study ◽  
Copy Number Variations ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

A Genome-Wide Association Study of Anxiety In A German Population Based Sample

2019 ◽  
Vol 29 ◽  
pp. S775
Author(s):  
Christiane Wolf ◽  
Katharina Domschke ◽  
Heike Weber ◽  
Christoph Schartner ◽  
Marcel Romanos ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Population Based ◽  
Genome Wide Association ◽  
German Population ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11504 ◽  
Author(s):  
Federico C. F. Calboli ◽  
Federica Tozzi ◽  
Nicholas W. Galwey ◽  
Athos Antoniades ◽  
Vincent Mooser ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Population Based ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis

Gut ◽  
2017 ◽  
Vol 67 (10) ◽  
pp. 1855-1863 ◽  
Author(s):  
Jonas Rosendahl ◽  
Holger Kirsten ◽  
Eszter Hegyi ◽  
Peter Kovacs ◽  
Frank Ulrich Weiss ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Clinical Importance ◽  
Population Based ◽  
Genome Wide Association ◽  
Expression Ratio ◽  
Alcoholic Chronic Pancreatitis ◽  
Genome Wide ◽  
A Genome

ObjectiveAlcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus.Design1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used.ResultsWe replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk.ConclusionAn inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.

Genome-wide association study identified copy number variants associated with sporadic colorectal cancer risk

2017 ◽  
Vol 55 (3) ◽  
pp. 181-188 ◽  
Author(s):  
Lai Fun Thean ◽  
Yee Syuen Low ◽  
Michelle Lo ◽  
Yik-Ying Teo ◽  
Woon-Puay Koh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Association Study ◽  
Copy Number ◽  
Genome Wide Association Study ◽  
Copy Number Variants ◽  
Genome Wide Association ◽  
Copy Number Loss ◽  
Genome Wide ◽  
A Genome

BackgroundMultiple single nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) risk. The role of structural or copy number variants (CNV) in CRC, however, remained unclear. We investigated the role of CNVs in patients with sporadic CRC.MethodsA genome-wide association study (GWAS) was performed on 1000 Singapore Chinese patients aged 50 years or more with no family history of CRC and 1000 ethnicity-matched, age-matched and gender-matched healthy controls using the Affymetrix SNP 6 platform. After 16 principal component corrections, univariate and multivariate segmentations followed by association testing were performed on 1830 samples that passed quality assurance tests.ResultsA rare CNV region (CNVR) at chromosome 14q11 (OR=1.92 (95% CI 1.59 to 2.32), p=2.7e-12) encompassing CHD8, and common CNVR at chromosomes 3q13.12 (OR=1.54 (95% CI 1.33 to 1.77), p=2.9e-9) and 12p12.3 (OR=1.69 (95% CI 1.41 to 2.01), p=2.8e-9) encompassing CD47 and RERG/ARHGDIB, respectively, were significantly associated with CRC risk. CNV loci were validated in an independent replication panel using an optimised copy number assay. Whole-genome expression data in matched tumours of a subset of cases demonstrated that copy number loss at CHD8 was significantly associated with dysregulation of several genes that perturb the Wnt, TP53 and inflammatory pathways.ConclusionsA rare CNVR at 14q11 encompassing the chromatin modifier CHD8 was significantly associated with sporadic CRC risk. Copy number loss at CHD8 altered expressions of genes implicated in colorectal tumourigenesis.

Sign in / Sign up

Export Citation Format

Share Document