scholarly journals Genome-wide study identifies association between HLA-B*55:01 and penicillin allergy

2020 ◽  
Author(s):  
Kristi Krebs ◽  
Jonas Bovijn ◽  
Maarja Lepamets ◽  
Jenny C Censin ◽  
Tuuli Jürgenson ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Meta Analysis ◽  
Strong Association ◽  
Hla Typing ◽  
Penicillin Allergy ◽  
P Value ◽  
Hypersensitivity Reactions ◽  
Hla Association ◽  
Genome Wide

AbstractBackgroundHypersensitivity reactions to drugs are often unpredictable and can be life-threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown.MethodsWe extracted data from the electronic health records of 52,000 Estonian and 500,000 UK biobank participants to study the role of genetic variation in the occurrence of penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from up to 22,554 and 488,377 individuals from the Estonian and UK cohorts, respectively, to further fine-map the human leukocyte antigen (HLA) association and replicated our results in two additional cohorts involving a total of 1.14 million individuals.ResultsGenome-wide meta-analysis of penicillin allergy revealed a significant association located in the HLA region on chromosome 6. The signal was further fine-mapped to the HLA-B*55:01 allele (OR 1.47 95% CI 1.37-1.58, P-value 4.63×10-26) and confirmed by independent replication in two cohorts. The meta-analysis of all four cohorts in the study revealed a strong association of HLA-B*55:01 allele with penicillin allergy (OR 1.33 95% CI 1.29-1.37, P-value 2.23×10-72). In silico follow-up suggests a potential effect on T lymphocytes at HLA-B*55:01.ConclusionWe present the first robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy.

scholarly journals Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin

PLoS Genetics ◽  
2014 ◽  
Vol 10 (12) ◽  
pp. e1004854 ◽  
Author(s):  
Anke Tönjes ◽  
Markus Scholz ◽  
Jana Breitfeld ◽  
Carola Marzi ◽  
Harald Grallert ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Meta Analysis ◽  
Genome Wide

scholarly journals The crucial role of genome-wide genetic variation in conservation

2021 ◽  
Vol 118 (48) ◽  
pp. e2104642118
Author(s):  
Marty Kardos ◽  
Ellie E. Armstrong ◽  
Sarah W. Fitzpatrick ◽  
Samantha Hauser ◽  
Philip W. Hedrick ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Environmental Changes ◽  
Population Viability ◽  
Adaptive Potential ◽  
Biodiversity Crisis ◽  
Genome Wide ◽  
Simulation Based ◽  
Functional Genetic Variation

The unprecedented rate of extinction calls for efficient use of genetics to help conserve biodiversity. Several recent genomic and simulation-based studies have argued that the field of conservation biology has placed too much focus on conserving genome-wide genetic variation, and that the field should instead focus on managing the subset of functional genetic variation that is thought to affect fitness. Here, we critically evaluate the feasibility and likely benefits of this approach in conservation. We find that population genetics theory and empirical results show that conserving genome-wide genetic variation is generally the best approach to prevent inbreeding depression and loss of adaptive potential from driving populations toward extinction. Focusing conservation efforts on presumably functional genetic variation will only be feasible occasionally, often misleading, and counterproductive when prioritized over genome-wide genetic variation. Given the increasing rate of habitat loss and other environmental changes, failure to recognize the detrimental effects of lost genome-wide genetic variation on long-term population viability will only worsen the biodiversity crisis.

Abstract 16160: Common Autosomal Variants are Associated With Bicuspid Aortic Valve in Turner Syndrome

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Siddharth Prakash ◽  
Michael Silberbach ◽  
Federico Asch ◽  
Giuseppe Limongelli ◽  
Hector Michelena ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Meta Analysis ◽  
Copy Number Variants ◽  
European Ancestry ◽  
P Value ◽  
Scaling Analysis ◽  
Aortic Valves ◽  
Genome Wide ◽  
Independent Review ◽  
Tests Of Association

Introduction: The prevalence of bicuspid aortic valves (BAV) is enriched thirty-fold in women with Turner Syndrome (TS) in comparison with the general population. Hypothesis: Common autosomal variants influence the development of BAV in TS women, who may be uniquely sensitized to these variants by the loss of one X chromosome. We sought to identify autosomal BAV susceptibility genes in a cohort of TS women (average age 30 years, 38% BAV, 18% coarctation). Methods: A total of 106 TS women of European ancestry with BAV and 173 TS women with tricuspid aortic valves were genotyped on Illumina Omni-Express arrays. Valve phenotypes were determined by independent review of echocardiograms from the enrolling sites. Tests of association were performed using logistic regression without adjustment for covariates and were summarized in a meta-analysis. Results: Xp dosage was inversely and quantitatively associated with BAV status (P=0.02). Large, recurrent copy number variants in 1p36.13, 3q29, 8p23.1 and 9p24.3 were significantly enriched in BAV cases. After exclusion of 26 outlier samples in multidimensional scaling analysis, there was no significant genomic inflation (lambda= 1.02). The strongest genome-wide association signals were observed in 1p36.23, 3q23, 12q21.2, 18q21 and 22q13.31, and did not overlap with previously reported loci for BAV. A total of 13 SNPs in 18q21 were positively associated with BAV (OR=2.5-4.3) with a minimum P value of 1x10-7. Replication of these regions in independent groups of cases is ongoing. Conclusion: Our results demonstrate that autosomal variants with large magnitudes of effect contribute to BAV in TS women, confirming our hypothesis, and provide evidence for gene-gene interactions in BAV formation.

Strong association between the 12q24 locus and sweet taste preference in the Japanese population revealed by genome-wide meta-analysis

2020 ◽  
Vol 65 (11) ◽  
pp. 939-947 ◽  
Author(s):  
Kaoru Kawafune ◽  
Tsuyoshi Hachiya ◽  
Shun Nogawa ◽  
Shoko Takahashi ◽  
Huijuan Jia ◽  
...  
Keyword(s):  
Japanese Population ◽  
Meta Analysis ◽  
Strong Association ◽  
Taste Preference ◽  
Sweet Taste ◽  
Genome Wide

Who Are the Victims and Who Are the Perpetrators in Dating Violence? Sharing the Role of Victim and Perpetrator

2017 ◽  
Vol 20 (5) ◽  
pp. 732-741 ◽  
Author(s):  
Sihyun Park ◽  
Sin-Hyang Kim
Keyword(s):  
Dating Violence ◽  
Web Of Science ◽  
Meta Analysis ◽  
Strong Association ◽  
Cycle Of Violence ◽  
Evidence Based ◽  
Single Group ◽  
Overlap Model ◽  
Study Participants

Background: Dating violence (DV) is a serious problem with devastating consequences. Often, research on DV has focused on two distinct groups: victims and perpetrators. However, there is growing evidence for a victim–perpetrator overlap model, which posits that those involved in DV are more likely to take on both roles, rather than either role on its own. Purpose: We investigated the patterns of involvement in DV among those who identified themselves as victims or perpetrators in previous studies. Method: This was a systematic review and meta-analysis. A total of 371 variables related to participants’ previous and concurrent experiences of DV victimization or perpetration (202 variables related to victimization and 169 related to perpetration) were identified in 25 studies, which were found by systematically searching three databases: PubMed, Web of Science, and SCOPUS. Results: The majority of previous studies categorized study participants as either DV victims or perpetrators; however, those who identified themselves as either DV victims or DV perpetrators were more likely to assume the opposite role as well. Specifically, current DV perpetrators had a strong association with previous or concurrent victimization experiences, and current DV victims were similarly likely to have assumed the roles of both victim and perpetrator in their histories. Conclusion: Further efforts should be put into avoiding categorization of those involved in violence; rather, they should be regarded as a single group. Additionally, evidence-based interventions should be developed for this population to help break the cycle of violence.

scholarly journals The crucial role of genome-wide genetic variation in conservation

2021 ◽  
Author(s):  
Martin Kardos ◽  
Ellie Armstrong ◽  
Sarah W Fitzpatrick ◽  
Samantha Hauser ◽  
Philip Hedrick ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Environmental Changes ◽  
Population Viability ◽  
Adaptive Potential ◽  
Biodiversity Crisis ◽  
Genome Wide ◽  
Simulation Based ◽  
Functional Genetic Variation

The unprecedented rate of extinction calls for efficient use of genetics to help conserve biodiversity. Several recent genomic and simulation-based studies have argued that the field of conservation biology has placed too much focus on the conservation of genome-wide genetic variation, and that this approach should be replaced with another that focuses instead on managing the subset of functional genetic variation that is thought to affect fitness. Here, we critically evaluate the feasibility and likely benefits of this approach in conservation. We find that population genetics theory and empirical results show that the conserving genome-wide genetic variation is generally the best approach to prevent inbreeding depression and loss of adaptive potential from driving populations towards extinction. Focusing conservation efforts on presumably functional genetic variation will only be feasible occasionally, often misleading, and counterproductive when prioritized over genome-wide genetic variation. Given the increasing rate of habitat loss and other environmental changes, failure to recognize the detrimental effects of lost genome-wide variation on long-term population viability will only worsen the biodiversity crisis.

scholarly journals A meta-analysis of the genome-wide association studies on two genetically correlated phenotypes (self-reported headache and self-reported migraine) identifies four new risk loci for headaches (N=397,385)

2021 ◽  
Author(s):  
Weihua Meng ◽  
Parminder Reel ◽  
Charvi Nangia ◽  
Aravind Rajendrakumar ◽  
Harry Hebert ◽  
...  
Keyword(s):  
Association Studies ◽  
Meta Analysis ◽  
The Self ◽  
Genome Wide Association ◽  
P Value ◽  
Clinical Settings ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Genetic Mechanisms ◽  
The Uk

Headache is one of the commonest complaints that doctors need to address in clinical settings. The genetic mechanisms of different types of headache are not well understood. In this study, we performed a meta-analysis of genome-wide association studies (GWAS) on the self-reported headache phenotype from the UK Biobank cohort and the self-reported migraine phenotype from the 23andMe resource using the metaUSAT for genetically correlated phenotypes (N=397,385). We identified 38 loci for headaches, of which 34 loci have been reported before and 4 loci were newly identified. The LRP1-STAT6-SDR9C7 region in chromosome 12 was the most significantly associated locus with a leading P value of 1.24 x 10-62 of rs11172113. The ONECUT2 gene locus in chromosome 18 was the strongest signal among the 4 new loci with a P value of 1.29 x 10-9 of rs673939. Our study demonstrated that the genetically correlated phenotypes of self-reported headache and self-reported migraine can be meta-analysed together in theory and in practice to boost study power to identify more new variants for headaches. This study has paved way for a large GWAS meta-analysis study involving cohorts of different, though genetically correlated headache phenotypes.

scholarly journals A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers

2021 ◽  
Vol 22 (19) ◽  
pp. 10389
Author(s):  
Negar Hosseinkhani ◽  
Mahdi Abdoli Shadbad ◽  
Mohammad Asghari Jafarabadi ◽  
Noora Karim Ahangar ◽  
Zahra Asadzadeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
T Cells ◽  
Cd8 T Cells ◽  
Meta Analysis ◽  
Strong Association ◽  
Positive Association ◽  
P Value ◽  
Immune Resistance ◽  
Current Systematic Review ◽  
Meta Analyses

Preclinical studies have indicated that T-cell immunoglobulin and ITIM domain (TIGIT) can substantially attenuate anti-tumoral immune responses. Although multiple clinical studies have evaluated the significance of TIGIT in patients with solid cancers, their results remain inconclusive. Thus, we conducted the current systematic review and meta-analysis based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) to determine its significance in patients with solid cancers. We systematically searched the Web of Science, Embase, PubMed, and Scopus databases to obtain peer-reviewed studies published before September 20, 2020. Our results have shown that increased TIGIT expression has been significantly associated with inferior overall survival (OS) (HR = 1.42, 95% CI: 1.11–1.82, and p-value = 0.01). Besides, the level of tumor-infiltrating TIGIT+CD8+ T-cells have been remarkably associated inferior OS and relapse-free survival (RFS) of affected patients (HR = 2.17, 95% CI: 1.43–3.29, and p-value < 0.001, and HR = 1.89, 95% CI: 1.36–2.63, and p-value < 0.001, respectively). Also, there is a strong positive association between TIGIT expression with programmed cell death-1 (PD-1) expression in these patients (OR = 1.71, 95% CI: 1.10–2.68, and p-value = 0.02). In summary, increased TIGIT expression and increased infiltration of TIGIT+CD8+ T-cells can substantially worsen the prognosis of patients with solid cancers. Besides, concerning the observed strong association between TIGIT and PD-1, ongoing clinical trials, and promising preclinical results, PD-1/TIGIT dual blockade can potentially help overcome the immune-resistance state seen following monotherapy with a single immune checkpoint inhibitor in patients with solid cancers.

scholarly journals Genome-Wide Analyses for Osteosarcoma in Leonberger Dogs Reveal the CDKN2A/B Gene Locus as a Major Risk Locus

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1964
Author(s):  
Anna Letko ◽  
Katie M. Minor ◽  
Elaine M. Norton ◽  
Voichita D. Marinescu ◽  
Michaela Drögemüller ◽  
...  
Keyword(s):  
Gene Locus ◽  
P Value ◽  
Chromosome 11 ◽  
Primary Bone Tumor ◽  
Genome Wide ◽  
Increased Risk ◽  
Canine Chromosome ◽  
Primary Bone ◽  
Coding Variants

Dogs represent a unique spontaneous cancer model. Osteosarcoma (OSA) is the most common primary bone tumor in dogs (OMIA 001441-9615), and strongly resembles human forms of OSA. Several large- to giant-sized dog breeds, including the Leonberger, have a greatly increased risk of developing OSA. We performed genome-wide association analysis with high-density imputed SNP genotype data from 273 Leonberger cases with a median age of 8.1 [3.1–13.5] years and 365 controls older than eight years. This analysis revealed significant associations at the CDKN2A/B gene locus on canine chromosome 11, mirroring previous findings in other dog breeds, such as the greyhound, that also show an elevated risk for OSA. Heritability (h2SNP) was determined to be 20.6% (SE = 0.08; p-value = 5.7 × 10−4) based on a breed prevalence of 20%. The 2563 SNPs across the genome accounted for nearly all the h2SNP of OSA, with 2183 SNPs of small effect, 316 SNPs of moderate effect, and 64 SNPs of large effect. As with many other cancers it is likely that regulatory, non-coding variants underlie the increased risk for cancer development. Our findings confirm a complex genetic basis of OSA, moderate heritability, and the crucial role of the CDKN2A/B locus leading to strong cancer predisposition in dogs. It will ultimately be interesting to study and compare the known genetic loci associated with canine OSA in human OSA.

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