scholarly journals Two-Phase Designs to Follow-Up Genome-Wide Association Signals With DNA Resequencing Studies

2013 ◽  
Vol 37 (3) ◽  
pp. 229-238 ◽  
Author(s):  
Daniel J. Schaid ◽  
Gregory D. Jenkins ◽  
James N. Ingle ◽  
Richard M. Weinshilboum
Keyword(s):  
Genome Wide Association ◽  
Two Phase ◽  
Genome Wide ◽  
Dna Resequencing

scholarly journals Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus(HPV) Infection

2019 ◽  
Author(s):  
Sally N. Adebamowo ◽  
Adebowale A Adeyemo ◽  
Charles N Rotimi ◽  
Olayinka Olaniyan ◽  
Richard B. Offiong ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Principal Component ◽  
Hpv Infection ◽  
Genome Wide Association ◽  
Replication Studies ◽  
Genome Wide

Abstract Background: Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. Methods: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p=1.43 x 10-6). The top variants associated with cervical hrHPV persistence were in DAP(OR: 6.86, p=7.15 x 10-8), NR5A2(OR: 3.65, p=2.03 x 10-7) and MIR365-2(OR: 7.71, p=2.63 x 10-7) gene regions. Conclusions: This exploratory GWAS yielded novel candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

scholarly journals Genome-Wide Association Study for Coronary Artery Calcification With Follow-Up in Myocardial Infarction

Circulation ◽  
2011 ◽  
Vol 124 (25) ◽  
pp. 2855-2864 ◽  
Author(s):  
Christopher J. O'Donnell ◽  
Maryam Kavousi ◽  
Albert V. Smith ◽  
Sharon L.R. Kardia ◽  
Mary F. Feitosa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Association Study ◽  
Coronary Artery Calcification ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide

scholarly journals Genome-wide association studies of cardiac electrical phenotypes

2020 ◽  
Vol 116 (9) ◽  
pp. 1620-1634
Author(s):  
Charlotte Glinge ◽  
Najim Lahrouchi ◽  
Reza Jabbari ◽  
Jacob Tfelt-Hansen ◽  
Connie R Bezzina
Keyword(s):  
Genetic Basis ◽  
Association Studies ◽  
Individual Variability ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Challenges And Opportunities ◽  
Electrocardiographic Parameters

Abstract The genetic basis of cardiac electrical phenotypes has in the last 25 years been the subject of intense investigation. While in the first years, such efforts were dominated by the study of familial arrhythmia syndromes, in recent years, large consortia of investigators have successfully pursued genome-wide association studies (GWAS) for the identification of single-nucleotide polymorphisms that govern inter-individual variability in electrocardiographic parameters in the general population. We here provide a review of GWAS conducted on cardiac electrical phenotypes in the last 14 years and discuss the implications of these discoveries for our understanding of the genetic basis of disease susceptibility and variability in disease severity. Furthermore, we review functional follow-up studies that have been conducted on GWAS loci associated with cardiac electrical phenotypes and highlight the challenges and opportunities offered by such studies.

scholarly journals Genome-wide association study of response to cognitive–behavioural therapy in children with anxiety disorders

2016 ◽  
Vol 209 (3) ◽  
pp. 236-243 ◽  
Author(s):  
Jonathan R. I. Coleman ◽  
Kathryn J. Lester ◽  
Robert Keers ◽  
Susanna Roberts ◽  
Charles Curtis ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Association Study ◽  
Treatment Response ◽  
Genome Wide Association Study ◽  
Behavioural Therapy ◽  
Post Treatment ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Cognitive Behavioural

BackgroundAnxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.AimsTo perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).MethodPresence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.ResultsNo variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.ConclusionsThis is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.

Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CLBL genes

2011 ◽  
Vol 18 (7) ◽  
pp. 959-965 ◽  
Author(s):  
Jezabel Varadé ◽  
Manuel Comabella ◽  
Miguel A Ortiz ◽  
Rafael Arroyo ◽  
Oscar Fernández ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Pooled Analysis ◽  
Replication Study ◽  
Genome Wide Association ◽  
Genome Wide

Background and objectives: Ten genes previously showing different evidence of association with multiple sclerosis have been selected to validate. Methods: Eleven polymorphisms were genotyped with the iPLEX™ Sequenom in a well-powered collection of Spanish origin including 2863 multiple sclerosis cases and 2930 controls. Results: Replication extended to the following polymorphisms: PKN2 (rs305217), GTF2B (rs7538427), EPHA4 (rs1517440), YTHDF3 (rs12115114), ANKFN1 (rs17758761) and PTPRM (rs4798571), which did not reach the threshold of significance in a follow-up of the first genome-wide association study (GWAS) conducted in multiple sclerosis; TMEM39A (rs1132200), which appeared as a newly identified susceptibility gene in the same study; a gene previously reaching GWAS significance in Italy, CBLB (rs9657904); IL12B (rs6887695, rs10045431), a susceptibility gene shared by diverse autoimmune diseases and, finally, another gene showing inconclusive association with multiple sclerosis, CNR1 (rs1049353). Conclusions: Pooled analysis corroborated the effect on MS predisposition of three genes: TMEM39A [rs1132200: pM-H=0.001; ORM-H (95% CI)= 0.84 (0.75–0.93)], IL12B [rs6887695: pM-H=0.03; ORM-H (95% CI)= 1.09 (1.01–1.17)] and CBLB [rs9657904: pM-H=0.01; ORM-H (95% CI)= 0.89 (0.81–0.97)].

Efficient estimation of disease odds ratios for follow-up genetic association studies

2017 ◽  
Vol 28 (7) ◽  
pp. 1927-1941
Author(s):  
Jiyuan Hu ◽  
Wei Zhang ◽  
Xinmin Li ◽  
Dongdong Pan ◽  
Qizhai Li
Keyword(s):  
Genetic Association ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Efficient Estimation ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Odds Ratios ◽  
Genome Wide ◽  
Follow Up Studies

In the past decade, genome-wide association studies have identified thousands of susceptible variants associated with complex human diseases and traits. Conducting follow-up genetic association studies has become a standard approach to validate the findings of genome-wide association studies. One problem of high interest in genetic association studies is to accurately estimate the strength of the association, which is often quantified by odds ratios in case-control studies. However, estimating the association directly by follow-up studies is inefficient since this approach ignores information from the genome-wide association studies. In this article, an estimator called GFcom, which integrates information from genome-wide association studies and follow-up studies, is proposed. The estimator includes both the point estimate and corresponding confidence interval. GFcom is more efficient than competing estimators regarding MSE and the length of confidence intervals. The superiority of GFcom is particularly evident when the genome-wide association study suffers from severe selection bias. Comprehensive simulation studies and applications to three real follow-up studies demonstrate the performance of the proposed estimator. An R package, “GFcom”, implementing our method is publicly available at https://github.com/JiyuanHu/GFcom .

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