scholarly journals Genome-wide association analysis of Russian wheat aphid (Diuraphis noxia) resistance in Dn4 derived wheat lines evaluated in South Africa

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244455
Author(s):  
Lavinia Kisten ◽  
Vicki L. Tolmay ◽  
Isack Mathew ◽  
Scott L. Sydenham ◽  
Eduard Venter
Keyword(s):  
South Africa ◽  
South African ◽  
The United States ◽  
Russian Wheat Aphid ◽  
Diuraphis Noxia ◽  
Genome Wide Association ◽  
Complex Genetics ◽  
Genome Wide ◽  
A Genome ◽  
Wheat Lines

Russian wheat aphid (RWA; Diuraphis noxia Kurdjumov) resistance on the 1D chromosome of wheat has been the subject of intensive research. Conversely, the deployment of the Dn4 derived RWA resistant varieties diminished in recent years due to the overcoming of the resistance it imparts in the United States of America. However, this resistance has not been deployed in South Africa despite reports that Dn4 containing genotypes exhibited varying levels of resistance against the South African RWA biotypes. It is possible that there may be certain genetic differences within breeding lines or cultivars that influence the expression of resistance. The aim of this study was to identify single nucleotide polymorphism (SNP) markers associated with resistance to South African RWA biotypes. A panel of thirty-two wheat lines were phenotyped for RWA resistance using four South African RWA biotypes and a total of 181 samples were genotyped using the Illumina 9K SNP wheat chip. A genome wide association study using 7598 polymorphic SNPs showed that the population was clustered into two distinct subpopulations. Twenty-seven marker trait associations (MTA) were identified with an average linkage disequilibrium of 0.38 at 10 Mbp. Four of these markers were highly significant and three correlated with previously reported quantitative trait loci linked to RWA resistance in wheat. Twenty putative genes were annotated using the IWGSC RefSeq, three of which are linked to plant defence responses. This study identified novel chromosomal regions that contribute to RWA resistance and contributes to unravelling the complex genetics that control RWA resistance in wheat.

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 Genome-Wide Association Study and Polygenic Risk Score Analysis of Posttraumatic Stress Disorder and Metabolic Syndrome in a South African Population

2021 ◽  
Vol 15 ◽  
Author(s):  
Patricia C. Swart ◽  
Leigh L. van den Heuvel ◽  
Cathryn M. Lewis ◽  
Soraya Seedat ◽  
Sian M. J. Hemmings
Keyword(s):  
Metabolic Syndrome ◽  
South African ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Stress Disorder ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Polygenic Risk ◽  
Genome Wide ◽  
A Genome

Posttraumatic stress disorder (PTSD) is a trauma-related disorder that frequently co-occurs with metabolic syndrome (MetS). MetS is characterized by obesity, dyslipidemia, and insulin resistance. To provide insight into these co-morbidities, we performed a genome-wide association study (GWAS) meta-analysis to identify genetic variants associated with PTSD, and determined if PTSD polygenic risk scores (PRS) could predict PTSD and MetS in a South African mixed-ancestry sample. The GWAS meta-analysis of PTSD participants (n = 260) and controls (n = 343) revealed no SNPs of genome-wide significance. However, several independent loci, as well as five SNPs in the PARK2 gene, were suggestively associated with PTSD (p < 5 × 10–6). PTSD-PRS was associated with PTSD diagnosis (Nagelkerke’s pseudo R2 = 0.0131, p = 0.00786), PTSD symptom severity [as measured by CAPS-5 total score (R2 = 0.00856, p = 0.0367) and PCL-5 score (R2 = 0.00737, p = 0.0353)], and MetS (Nagelkerke’s pseudo R2 = 0.00969, p = 0.0217). These findings suggest an association between PTSD and PARK2, corresponding with results from the largest PTSD-GWAS conducted to date. PRS analysis suggests that genetic variants associated with PTSD are also involved in the development of MetS. Overall, the results contribute to a broader goal of increasing diversity in psychiatric genetics.

scholarly journals Sex Differences in the Genetics of Sarcoidosis Across European and African Ancestry Populations

2021 ◽  
Author(s):  
Ying Xiong ◽  
Susanna Kullberg ◽  
Lori Garman ◽  
Nathan Pezant ◽  
David Ellinghaus ◽  
...  
Keyword(s):  
Sex Differences ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
The United States ◽  
Genetic Variations ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome ◽  
Löfgren’S Syndrome

Abstract Background: Sex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations in two sarcoidosis clinical phenotypes: Löfgren's syndrome (LS) and non- Löfgren's syndrome (non-LS).Methods: A meta-analysis of genome-wide association studies was conducted in Europeans and African Americans, totaling 10,103 individuals from three population-based cohorts, Sweden (n = 3,843), Germany (n = 3,342), and the United States (n = 2,918), followed by replication look-up in the UK Biobank (n = 387,945). A genome-wide association study based on Immunochip data consisting of 141,000 single nucleotide polymorphisms (SNPs) was conducted in males and females in each cohort, respectively. The association test was based on logistic regression using the additive model in LS and non-LS independently. Additionally, gene-based analysis, expression quantitative trait loci (eQTL) assessments, and enrichment analysis were performed to discover functionally relevant mechanisms related to biological sex. Results: In LS sarcoidosis, we identified various sex-dependent genetic variations (798 SNPs in males and 703 SNPs in females). Genetic findings in sex groups were explicitly located in the extended major histocompatibility complex. In non-LS, we detected 16 SNPs in males and 38 in females, primarily localized to the MHC class II region. Additionally, the ANXA11 gene, a well-documented locus in sarcoidosis, was associated exclusively with non-LS males. Gene-based, eQTL assessment and enrichment analyses revealed distinct sex-dependent genomic loci and gene expression variation in the sex groups. Conclusions: Our findings provide new evidence of the existence of sex-dependent genetic variations underlying sarcoidosis genetic architecture. These findings suggest a sex bias in molecular mechanisms of sarcoidosis.

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.

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 Genome-Wide Association Study of Opioid Cessation

2020 ◽  
Vol 9 (1) ◽  
pp. 180 ◽  
Author(s):  
Jiayi W. Cox ◽  
Richard M. Sherva ◽  
Kathryn L. Lunetta ◽  
Emma C. Johnson ◽  
Nicholas G. Martin ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Chronic Back Pain ◽  
The United States ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Risk Scores ◽  
Opioid Use ◽  
Genome Wide ◽  
A Genome

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.

scholarly journals Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 106
Author(s):  
Baihan Wang ◽  
Olga Giannakopoulou ◽  
Isabelle Austin-Zimmerman ◽  
Haritz Irizar ◽  
Jasmine Harju-Seppänen ◽  
...  
Keyword(s):  
Verbal Memory ◽  
Verbal Learning ◽  
The United States ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Short Delay ◽  
Genome Wide ◽  
A Genome ◽  
Atpase Gene

Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study®, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.

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