scholarly journals Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol

2022 ◽  
Author(s):  
Ben Gaastra ◽  
Sheila Alexander ◽  
Mark K. Bakker ◽  
Hemant Bhagat ◽  
Philippe Bijlenga ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Subarachnoid Haemorrhage ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Statistical Significance ◽  
Genome Wide Association ◽  
Aneurysmal Subarachnoid Haemorrhage ◽  
Nucleotide Polymorphisms ◽  
Public Network ◽  
Genome Wide

AbstractAneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1–24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network.

scholarly journals Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color

2021 ◽  
Vol 7 (11) ◽  
pp. eabd1239
Author(s):  
Mark Simcoe ◽  
Ana Valdes ◽  
Fan Liu ◽  
Nicholas A. Furlotte ◽  
David M. Evans ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Color Variation ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Melanin Pigmentation ◽  
Eye Color ◽  
Human Eye ◽  
Genome Wide ◽  
Genomic Regions

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.

scholarly journals Genome-Wide Association Study (GWAS) for Examining the Genomics Controlling Prickle Production in Red Raspberry (Rubus idaeus L.)

Agronomy ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Archana Khadgi ◽  
Courtney A. Weber
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genomic Region ◽  
Rubus Idaeus ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Red Raspberry ◽  
Genome Wide ◽  
A Genome ◽  
Genotype By Sequencing

Red raspberry (Rubus idaeus L.) is an expanding high-value berry crop worldwide. The presence of prickles, outgrowths of epidermal tissues lacking vasculature, on the canes, petioles, and undersides of leaves complicates both field management and harvest. The utilization of cultivars with fewer prickles or prickle-free canes simplifies production. A previously generated population segregating for prickles utilizing the s locus between the prickle-free cultivar Joan J (ss) and the prickled cultivar Caroline (Ss) was analyzed to identify the genomic region associated with prickle development in red raspberry. Genotype by sequencing (GBS) was combined with a genome-wide association study (GWAS) using fixed and random model circulating probability unification (FarmCPU) to analyze 8474 single nucleotide polymorphisms (SNPs) and identify significant markers associated with the prickle-free trait. A total of four SNPs were identified on chromosome 4 that were associated with the phenotype and were located near or in annotated genes. This study demonstrates how association genetics can be used to decipher the genetic control of important horticultural traits in Rubus, and provides valuable information about the genomic region and potential genes underlying the prickle-free trait.

Abstract 4437: Genome-Wide Association Study for the Response to Antihypertensive Medication: HOMED-BP-GENE Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tomohiro Katsuya ◽  
Kei Asayama ◽  
Ryusuke Inoue ◽  
Ken Sugimoto ◽  
Takayoshi Ohkubo ◽  
...  
Keyword(s):  
Association Study ◽  
Antihypertensive Medication ◽  
Genome Wide Association Study ◽  
Early Morning ◽  
Home Blood Pressure ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome ◽  
Drug Responsiveness

AAntihypertensive therapy is a powerful approach to prevent the cardiovascular disease. However, the responsiveness of the therapy is highly individual due to the variability of genetic or environmental factors. To elucidate the genetic background underlying antihypertensive drug responsiveness, we carried out a genome-wide association study (GWAS). The subjects studied were recruited from the participants of HOMED-BP study (UMIN Registered ID C000000137, http://www.cpt.med.tohoku.ac.jp/HOMED-BP/) after obtaining the informed consent for the genetic analysis. After DNA extraction from peripheral blood, about half million single nucleotide polymorphisms (SNPs) were examined using GeneChip Genome-Wide Human SNP5.0 Array (Affymetrix). Home blood pressure (HBP) was measured every day within 1 hour after wake-up and before going to bed using HEM747-IC-N (Omron). The study protocol was approved by the ethical committee of Osaka University. SNP5.0 Array analysis was demonstrated for 300 participants. Antihypertensive therapy for 4weeks decreased their average HBP from 149.9/88.8mmHg to 137.7/82.2mmHg in early morning and 142.6/82.3mmHg to 129.1/74.7mmHg before going to bed. We excluded the SNPs data that showed low call rate, lack of Hardy-Weinberg’s equilibrium and minor allele frequency less than 0.05. Eight SNPs were significantly (p<0.001) associated with mean HBP reduction both in the early morning and at bedtime. Nine SNPs were more significantly (p<0.0001) associated with morning HBP reduction and 3 SNPs were associated with bedtime HBP reduction. In conclusion, GWAS of antihypertensive medication revealed several candidate loci responsible for a month therapy with the difference between morning and evening.

scholarly journals Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study

Brain ◽  
2020 ◽  
Author(s):  
Longfei Jia ◽  
Fangyu Li ◽  
Cuibai Wei ◽  
Min Zhu ◽  
Qiumin Qu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Predictive Models ◽  
Genome Wide Association Study ◽  
Disease Onset ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Risk Variants ◽  
Genome Wide

Abstract Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer’s disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer’s disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer’s disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10−19, 2.49 × 10−23, 1.35 × 10−67, and 4.81 × 10−9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P &lt; 5.0 × 10−8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer’s disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer’s disease, suggesting that our models can predict Alzheimer’s disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer’s disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer’s disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.

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