scholarly journals 3354 Biomedical Informatics/Health Informatics A Preliminary Study of Glaucoma: The Intersection of Genetics and Survey Data from the Health and Retirement Study

2019 ◽  
Vol 3 (s1) ◽  
pp. 26-27
Author(s):  
Jessica Cooke Bailey ◽  
Tyler G. Kinzy ◽  
Nicholas K. Schiltz
Keyword(s):  
Risk Factors ◽  
Genome Wide Association Study ◽  
The United States ◽  
Genome Wide Association ◽  
Health And Retirement Study ◽  
Inherited Disease ◽  
Social Security Administration ◽  
Genome Wide ◽  
A Genome ◽  
Retirement Study

OBJECTIVES/SPECIFIC AIMS: Glaucoma is a leading cause of irreversible blindness worldwide; in the United States alone, over 2.7 million individuals are affected. Various risk factors for glaucoma are known and include age, race/ethnicity, genetics, and ocular measures. Despite numerous studies, molecular and environmental factors that contribute to glaucoma remain elusive. Our objective was to conduct a genome-wide association for glaucoma among black and white HRS respondents, and to determine the feasibility for future analyses examining shared genetic markers between glaucoma and other comorbidities, behaviors, and environmental risk factors. METHODS/STUDY POPULATION: The University of Michigan Health and Retirement Study (HRS) is a longitudinal survey of a representative sample of Americans over the age of 50. Supported by the National Institute on Aging and the Social Security Administration, the HRS is designed to provide reliable data on the decisions, choices, and behaviors of people as they age and respond to changes in public policy, the economy, and health. The study obtains information every two years about income and wealth, health and use of health services, work and retirement, and family connections. Through its unique and in-depth interviews, the HRS provides an invaluable and growing body of multidisciplinary data that researchers can use to address important questions about the challenges and opportunities of aging. Because of its innovation and importance, the HRS has become the model and hub for a growing network of harmonized longitudinal aging studies around the world. Saliva was collected on half of the HRS sample each wave starting in 2006 and respondents were genotyped on the Illumina Human Omni2.5-Quad (Omni2.5) BeadChip at the NIH Center for Inherited Disease Research. We accessed survey results to evaluate prevalence of glaucoma in this dataset and performed a genome-wide association study (GWAS) adjusting for age, sex, and significant Principal Components and stratifying by self-reported race (White / Black). RESULTS/ANTICIPATED RESULTS: Of 8179 respondents passing quality filters, 6409 (78.40%) were white and 985 (12.05%) were black. Self-reported glaucoma prevalence was 7.85% and 16.34% in white and black respondents, respectively. White respondents had a mean age of 76.97 (SD 7.53) and were 57.25% female. Black respondents had a similar mean age of 74.96 (SD 7.27) and were 62.54% female. More than 87% of both groups were assessed in 2012. Preliminary GWAS analyses did not replicate known glaucoma loci and no variants attained genome-wide significance. A suggestive variant (p<1e-05) in the black population was within 10kb of a known locus, rs1196998. Future analyses will evaluate genetic association with combinations of glaucoma and comorbidities. DISCUSSION/SIGNIFICANCE OF IMPACT: Glaucoma risk is higher in minority groups than in whites, and the majority of reported genetic studies of glaucoma have been performed in individuals of European descent. It is imperative to better understand the role of genetics, environment, and health behavior in glaucoma risk. Further, understanding common mechanisms underlying diseases that co-occur with glaucoma could illuminate novel disease mechanisms that can be targeted for early intervention and/or treatment.

scholarly journals Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study

2009 ◽  
Vol 8 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Simon Mead ◽  
Mark Poulter ◽  
James Uphill ◽  
John Beck ◽  
Jerome Whitfield ◽  
...  
Keyword(s):  
Risk Factors ◽  
Association Study ◽  
Genetic Risk ◽  
Genome Wide Association Study ◽  
Genetic Risk Factors ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Jakob Disease

scholarly journals Genome-wide association study implicates CHRNA2 in cannabis use disorder

2017 ◽  
Author(s):  
Ditte Demontis ◽  
Veera Manikandan Rajagopal ◽  
Thomas D. Als ◽  
Jakob Grove ◽  
Jonatan Pallesen ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Significant Risk ◽  
The United States ◽  
Cannabis Use ◽  
Genome Wide Association ◽  
Cannabis Use Disorder ◽  
Genome Wide ◽  
Independent Population ◽  
A Genome

Introductory paragraphCannabis is the most frequently used illicit psychoactive substance worldwide1. Life time use has been reported among 35-40% of adults in Denmark2 and the United States3. Cannabis use is increasing in the population4–6 and among users around 9% become dependent7. The genetic risk component is high with heritability estimates of 518–70%9. Here we report the first genome-wide significant risk locus for cannabis use disorder (CUD, P=9.31×10−12) that replicates in an independent population (Preplication=3.27×10−3, Pmetaanalysis=9.09×10−12). The finding is based on a genome-wide association study (GWAS) of 2,387 cases and 48,985 controls followed by replication in 5,501 cases and 301,041 controls. The index SNP (rs56372821) is a strong eQTL for CHRNA2 and analyses of the genetic regulated gene expressions identified significant association of CHRNA2 expression in cerebellum with CUD. This indicates a potential therapeutic use in CUD of compounds with agonistic effect on the neuronal acetylcholine receptor alpha-2 subunit encoded by CHRNA2. At the polygenic level analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance.

scholarly journals A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior

2018 ◽  
Vol 17 ◽  
pp. 117693511877510 ◽  
Author(s):  
Yi Yang ◽  
Saonli Basu ◽  
Lisa Mirabello ◽  
Logan Spector ◽  
Lin Zhang
Keyword(s):  
Risk Factors ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Bone Cancer ◽  
Genome Wide Association ◽  
Ratio Test ◽  
Data Set ◽  
Estrogen Receptor Signaling ◽  
Genome Wide ◽  
A Genome

Osteosarcoma is considered to be the most common primary malignant bone cancer among children and young adults. Previous studies suggest growth spurts and height to be risk factors for osteosarcoma. However, studies on the genetic cause are still limited given the rare occurrence of the disease. In this study, we investigated in a family trio data set that is composed of 209 patients and their unaffected parents and conducted a genome-wide association study (GWAS) to identify genetic risk factors for osteosarcoma. We performed a Bayesian gene-based GWAS based on the single-nucleotide polymorphism (SNP)-level summary statistics obtained from a likelihood ratio test of the trio data, which uses a hierarchically structured prior that incorporates the SNP-gene hierarchical structure. The Bayesian approach has higher power than SNP-level GWAS analysis due to the reduced number of tests and is robust by accounting for the correlations between SNPs so that it borrows information across SNPs within a gene. We identified 217 genes that achieved genome-wide significance. Ingenuity pathway analysis of the gene set indicated that osteosarcoma is potentially related to TP53, estrogen receptor signaling, xenobiotic metabolism signaling, and RANK signaling in osteoclasts.

scholarly journals Genome-Wide Association Study Identifies Germline Polymorphisms Associated with Relapse of Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 878-878
Author(s):  
Jun J. Yang ◽  
Cheng Cheng ◽  
Devidas Meenakshi ◽  
Xueyuan Cao ◽  
Dario Campana ◽  
...  
Keyword(s):  
Risk Factors ◽  
Treatment Outcome ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Lymphoblastic Leukemia ◽  
Genetic Variations ◽  
Genome Wide Association ◽  
Childhood All ◽  
Genome Wide ◽  
A Genome

Abstract Abstract 878 Introduction: Treatment outcome of childhood acute lymphoblastic leukemia (ALL) has improved dramatically in the last 40 years thanks to risk-directed therapy. However, a substantial proportion of patients still experience relapse, many of whom have no known risk factors. Prior efforts to improve risk stratification have primarily focused on genetic variations of the tumor (e.g., cytogenetic abnormalities) or on assessment of early antileukemic response (e.g., upfront prednisone response, minimal residual disease [MRD] after remission induction). The role of inherited genetic variation on treatment response in children with ALL is poorly characterized. Methods: We performed a genome-wide association study to evaluate the association of genotypes at 444,044 germline SNPs with the risk of relapse in 2,535 children with newly diagnosed ALL enrolled on 5 frontline clinical trials: St. Jude Total Therapy XIIIB, XV, the Children's Oncology Group (COG) P9904, P9905, and P9906 protocols. The associations between SNP genotypes and ALL relapse were evaluated by Gray's test and by Fine and Gray's hazard regression model, adjusting for genetic ancestry and treatment regimens. To identify SNPs reproducibly associated with relapse across treatment regimens, we performed 100 rounds of discovery and replication, each round dividing patients into 2 cohorts at a 1:1 ratio. Each time, we used the discovery cohort to perform a genome-wide screen, and then filtered SNPs based on their association in the replication cohort. Finally, SNPs were prioritized on the basis of the number of times their association with relapse was replicated. Results: A total of 134 SNPs, representing 88 genomic loci, were replicated in at least 10 rounds of discovery-replication tests. Across the genome, the strongest association with relapse risk was observed at 14q22.1 in the PYGL gene (rs7142143). Each copy of the C allele at this PYGL intronic SNP (rs7142143) conferred a 3.6-fold increase in the hazard rate of relapse (P=6.7×10−9) and the association of this SNP with relapse was replicated in 79 of 100 rounds of discovery-replication tests. Of 134 relapse SNPs, 73 were associated with one or more known prognostic clinical features in childhood ALL: 32 SNPs were related to leukocyte count ≥50,000/μl at diagnosis; 19 were enriched in children older than 10 years of age; 16 were associated with hyperdiploid ALL (DNA index ≥ 1.16); and 61 were associated with ALL molecular subtype and/or lineage (MLL rearrangements, ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, or T-cell ALL). Interestingly, 110 of the 134 relapse SNPs (82%) were prognostic even among MRD-negative patients, and 133 (99%) remained significantly associated with relapse after adjusting for all known risk factors, strongly indicating the potential value of germline genetic variations in ALL risk classification. To explore the mechanisms by which SNPs might influence treatment outcome of ALL, we examined the association of the 134 relapse SNPs with four pharmacokinetic and pharmacodynamic endophenotypes in the St. Jude Total XIIIB and XV cohorts: methotrexate plasma clearance, intracellular accumulation of polyglutamated (active) methotrexate, dexamethasone plasma clearance, and asparaginase antibody levels. Fourteen of the 134 relapse SNPs were significantly associated with at least one of the four pharmacologic phenotypes in a manner consistent with a pharmacokinetically intuitive association with relapse (i.e., lower drug exposure translated into a higher risk of relapse). Conclusion: In this genome-wide association study, we systematically identified host genetic variations related to treatment outcome of childhood ALL, most of which were prognostic independent of known risk factors for relapse, and some also influenced outcome by affecting host disposition of antileukemic drugs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Genetic Risk Factors for Colorectal Cancer in Multiethnic Indonesians

2019 ◽  
Author(s):  
Irawan Yusuf ◽  
Upik A. Miskad ◽  
Ronald E. Lusikooy ◽  
Arham Arsyad ◽  
Akram Irwan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Cancer Risk ◽  
Genome Wide Association Study ◽  
Risk Model ◽  
Bayesian Variable Selection ◽  
Colorectal Cancer Risk ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

AbstractPurposeColorectal cancer is a common cancer in Indonesia, yet it has been understudied. We conduct a genome-wide association study focused on evaluation and discovery of colorectal cancer risk factors in Indonesians.MethodsWe administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique.ResultsWe replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk.ConclusionsThis work helps characterize the relationship between variants in theSCL22A3,SCG5,GREM1, andSTXBP5-AS1genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.

scholarly journals Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study

2016 ◽  
Vol 23 (8) ◽  
pp. 587-594 ◽  
Author(s):  
Yeting Du ◽  
Monica Ter-Minassian ◽  
Lauren Brais ◽  
Nichole Brooks ◽  
Amanda Waldron ◽  
...  
Keyword(s):  
Risk Factors ◽  
Small Intestine ◽  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Genetic Risk ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Dana Farber Cancer Institute ◽  
Genome Wide ◽  
A Genome

The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted.

scholarly journals Genome-wide association study reveals an independent genetic basis of zinc and cadmium concentrations in fresh sweet corn kernels

2021 ◽  
Author(s):  
Matheus Baseggio ◽  
Matthew Murray ◽  
Di Wu ◽  
Gregory Ziegler ◽  
Nicholas Kaczmar ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Sweet Corn ◽  
The United States ◽  
Zinc Homeostasis ◽  
Genome Wide Association ◽  
Elemental Profile ◽  
Genome Wide ◽  
A Genome ◽  
Corn Kernels

AbstractDespite being one of the most consumed vegetables in the United States, the elemental profile of sweet corn (Zea mays L.) is limited in its dietary contributions. To address this through genetic improvement, a genome-wide association study was conducted for the concentrations of 15 elements in fresh kernels of a sweet corn association panel. In concordance with mapping results from mature maize kernels, we detected a probable pleiotropic association of zinc and iron concentrations with nicotianamine synthase5 (nas5), which purportedly encodes an enzyme involved in synthesis of the metal chelator nicotianamine. Additionally, a pervasive association signal was identified for cadmium concentration within a recombination suppressed region on chromosome 2. The likely causal gene underlying this signal was heavy metal ATPase 3 (hma3), whose counterpart in rice, OsHMA3, mediates vacuolar sequestration of cadmium and zinc in roots, whereby regulating zinc homeostasis and cadmium accumulation in grains. Consistent with transgenic studies in rice, we detected an association of hma3 with cadmium but not zinc accumulation in fresh kernels. This finding implies that selection for low cadmium will not affect zinc levels in fresh kernels. Although less resolved association signals were detected for boron, nickel, and calcium, all 15 elements were shown to have moderate predictive abilities via whole- genome prediction. Collectively, these results help improve our genomics-assisted breeding efforts centered on improving the elemental profile of fresh sweet corn kernels.

Abstract WP132: A Genome Wide Association Study in Patients with Symptomatic Intracranial Atherostenosis

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Juan F Arenillas ◽  
Caty Carrera ◽  
Natàlia Cullell ◽  
Javier Reyes ◽  
Pedro L Muñoz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Association Study ◽  
Genetic Background ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Vascular Risk ◽  
Factors Associated ◽  
Genome Wide ◽  
A Genome ◽  
Caucasian Patients

Introduction and objective: Intracranial atherosclerosis (ICAS) is a major cause of stroke worldwide, and its genetic background remains largely unexplored. The previous studies performed have been based on candidate-gene strategy. We aimed to perform a genome-wide association study (GWAs) to find genetic risk factors associated with symptomatic ICAS. Methods: We studied a cohort of 83 Caucasian patients with ischemic stroke attributed to symptomatic ICAS and 315 controls genotyped with Human Core Exome (Illumina). A score combining number and severity of intracranial stenoses was used to assess ICAS severity in each patient. Quality controls, 1000G imputation and association analysis were performed through PLINK, R, IMPUTE2 and SNPTEST software following previous recommendations. Sex, age, principal components and vascular risk factors were used as covariates. Results: Several loci with a genome wide significant association (P<1E-08) were found to be associated with ICAS severity score. The most robust association was found for locus in chromosome 18 (p=3.05E-14). Conclusion: This GWAS in symptomatic ICAS patients has revealed potential genes associated with ICAS presence and severity. These findings need to be replicated in other cohorts, ideally in patients from different ethnicities.

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