scholarly journals The Role of 39 Psoriasis Risk Variants on Age of Psoriasis Onset

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Yingchang Lu ◽  
Sinae Kane ◽  
Haoyan Chen ◽  
Argentina Leon ◽  
Ethan Levin ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Risk Alleles ◽  
False Discovery ◽  
Risk Variants ◽  
Genome Wide ◽  
Independent Cohort

Recent genome-wide association studies (GWAS) have identified multiple genetic risk factors for psoriasis, but data on their association with age of onset have been marginally explored. The goal of this study was to evaluate known risk alleles of psoriasis for association with age of psoriasis onset in three well-defined case-only cohorts totaling 1,498 psoriasis patients. We selected 39 genetic variants from psoriasis GWAS and tested these variants for association with age of psoriasis onset in a meta-analysis. We found that rs10484554 and rs12191877 near HLA-C and rs17716942 near IFIH1 were associated with age of psoriasis onset with false discovery rate < 0.05. The association between rs17716942 and age of onset was not replicated in a fourth independent cohort of 489 patients (). The imputed HLA-C*06:02 allele demonstrated a much stronger association with age of psoriasis onset than rs10484554 and rs12191877. We conclude that despite the discovery of numerous psoriasis risk alleles, HLA-C*06:02 still plays the most important role in determining the age of onset of psoriasis. Larger studies are needed to evaluate the contribution of other risk alleles, including IFIH1, to age of psoriasis onset.

scholarly journals Host Genetic Variants Potentially Associated with SARS-Cov-2: A Multi-Population Analysis

2020 ◽  
Author(s):  
Maria K. Smatti ◽  
Yasser Al-Sarraj ◽  
Omar Albagha ◽  
Hadi M. Yassine
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Population Analysis ◽  
Fold Change ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Risk Alleles ◽  
Risk Variants ◽  
Genome Wide ◽  
Ifn Γ

Background: Clinical outcomes of Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) showed enormous inter-individual and interpopulation differences, possibly due to host genetics differences. Earlier studies identified single nucleotide polymorphisms (SNPs) associated with SARS-CoV-1 in Eastern Asian (EAS) populations. In this report, we aimed at exploring the frequency of a set of genetic polymorphisms that could affect SARS-CoV-2 susceptibility or severity, including those that were previously associated with SARS-CoV-1. Methods: We extracted the list of SNPs that could potentially modulate SARS-CoV-2 from the genome wide association studies (GWAS) on SARS-CoV-1 and other viruses. We also collected the expression data of these SNPs from the expression quantitative trait loci (eQTLs) databases. Sequences from Qatar Genome Programme (QGP, n=6,054) and 1000Genome project were used to calculate and compare allelic frequencies (AF). Results: A total of 74 SNPs, located in 10 genes: ICAM3, IFN-γ, CCL2, CCL5, AHSG, MBL, Furin, TMPRSS2, IL4, and CD209 promoter, were identified. Analysis of Qatari genomes revealed significantly lower AF of risk variants linked to SARS-CoV-1 severity (CCL2, MBL, CCL5, AHSG, and IL4) compared to that of 1000Genome and/or the EAS population (up to 25-fold change). Conversely, SNPs in TMPRSS2, IFN-γ, ICAM3, and Furin were more common among Qataris (average 2-fold change). Inter-population analysis showed that the distribution of risk alleles among Europeans differs substantially from Africans and EASs. Remarkably, Africans seem to carry extremely lower frequencies of SARS-CoV-1 susceptibility alleles, reaching to 32-fold decrease compared to other populations. Conclusion: Multiple genetic variants, which could potentially modulate SARS-CoV-2 infection, are significantly variable between populations, with the lowest frequency observed among Africans. Our results highlight the importance of exploring population genetics to understand and predict COVID-19 outcomes. Indeed, further studies are needed to validate these findings as well as to identify new genetic determinants linked to SARS-CoV-2.

scholarly journals Identification of four novel associations for B-cell acute lymphoblastic leukaemia risk

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jayaram Vijayakrishnan ◽  
Maoxiang Qian ◽  
James B. Studd ◽  
Wenjian Yang ◽  
Ben Kinnersley ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
B Cell ◽  
Lymphoblastic Leukaemia ◽  
Association Studies ◽  
Meta Analysis ◽  
Chromatin Interaction ◽  
Genome Wide Association Studies ◽  
Specific Effects ◽  
Risk Variants ◽  
Genome Wide

AbstractThere is increasing evidence for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children. To identify new risk variants for B-cell ALL (B-ALL) we conducted a meta-analysis with four GWAS (genome-wide association studies), totalling 5321 cases and 16,666 controls of European descent. We herein describe novel risk loci for B-ALL at 9q21.31 (rs76925697, P = 2.11 × 10−8), for high-hyperdiploid ALL at 5q31.1 (rs886285, P = 1.56 × 10−8) and 6p21.31 (rs210143 in BAK1, P = 2.21 × 10−8), and ETV6-RUNX1 ALL at 17q21.32 (rs10853104 in IGF2BP1, P = 1.82 × 10−8). Particularly notable are the pleiotropic effects of the BAK1 variant on multiple haematological malignancies and specific effects of IGF2BP1 on ETV6-RUNX1 ALL evidenced by both germline and somatic genomic analyses. Integration of GWAS signals with transcriptomic/epigenomic profiling and 3D chromatin interaction data for these leukaemia risk loci suggests deregulation of B-cell development and the cell cycle as central mechanisms governing genetic susceptibility to ALL.

Principals about principal components in statistical genetics

2018 ◽  
Vol 20 (6) ◽  
pp. 2200-2216 ◽  
Author(s):  
Fentaw Abegaz ◽  
Kridsadakorn Chaichoompu ◽  
Emmanuelle Génin ◽  
David W Fardo ◽  
Inke R König ◽  
...  
Keyword(s):  
Principal Components ◽  
Rare Variants ◽  
Association Studies ◽  
Meta Analysis ◽  
Principal Component ◽  
Statistical Genetics ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Study Results

Abstract Principal components (PCs) are widely used in statistics and refer to a relatively small number of uncorrelated variables derived from an initial pool of variables, while explaining as much of the total variance as possible. Also in statistical genetics, principal component analysis (PCA) is a popular technique. To achieve optimal results, a thorough understanding about the different implementations of PCA is required and their impact on study results, compared to alternative approaches. In this review, we focus on the possibilities, limitations and role of PCs in ancestry prediction, genome-wide association studies, rare variants analyses, imputation strategies, meta-analysis and epistasis detection. We also describe several variations of classic PCA that deserve increased attention in statistical genetics applications.

scholarly journals The Genetic Architecture of Gliomagenesis–Genetic Risk Variants Linked to Specific Molecular Subtypes

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2001 ◽  
Author(s):  
Wendy Yi-Ying Wu ◽  
Gunnar Johansson ◽  
Carl Wibom ◽  
Thomas Brännström ◽  
Annika Malmström ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Molecular Subtypes ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Molecular Alterations ◽  
Risk Variants ◽  
Genome Wide ◽  
Increased Risk ◽  
Genetic Risk Variants

Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including IDH-mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in TERT and TP53 were associated with increased risk of all glioma subtypes. Second, variants in CDKN2B-AS1, EGFR, and RTEL1 were associated with IDH-wildtype glioma. Third, variants in CCDC26 (the 8q24 locus), C2orf80 (close to IDH), LRIG1, PHLDB1, ETFA, MAML2 and ZBTB16 were associated with IDH-mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.

scholarly journals A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry

2020 ◽  
Vol 4 (1) ◽  
pp. 181-190 ◽  
Author(s):  
Zhaohui Du ◽  
Niels Weinhold ◽  
Gregory Chi Song ◽  
Kristin A. Rand ◽  
David J. Van Den Berg ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Association Studies ◽  
Meta Analysis ◽  
African Ancestry ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Admixture Mapping ◽  
Genome Wide Association Studies ◽  
Risk Alleles ◽  
Genome Wide

Abstract Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P &lt; 1 × 10−6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P &lt; .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10−12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

scholarly journals Identifying 31 novel breast cancer susceptibility loci using data from genome-wide association studies conducted in Asian and European women

2019 ◽  
Author(s):  
Xiang Shu ◽  
Jirong Long ◽  
Qiuyin Cai ◽  
Sun-Seog Kweon ◽  
Ji-Yeob Choi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Asian Populations ◽  
Risk Variants ◽  
Genome Wide ◽  
European Women

ABSTRACTCommon genetic variants in 183 loci have been identified in relation to breast cancer risk in genome-wide association studies (GWAS). These risk variants combined explain only a relatively small proportion of breast cancer heritability, particularly in Asian populations. To search for additional genetic susceptibility loci for breast cancer, we performed a meta-analysis of data from GWAS conducted in Asians (24,206 cases and 24,775 controls). Variants showing an association with breast cancer risk at P < 0.01 were evaluated in GWAS conducted in European women including 122,977 cases and 105,974 controls. In the combined analysis of data from both Asian and European women, the lead variant in 28 loci not previously reported showed an association with breast cancer risk at P < 5 ×10−8. In the meta-analysis of all GWAS data from Asian and European descendants, we identified SNPs in three additional loci in association with breast cancer risk at P < 5 ×10−8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). Expression quantitative trait locus (eQTL) and gene-based analyses provided evidence for the possible involvement of the YBEY, MAN2C1, SNUPN, TBX1, SEMA4A, STC1, MUTYH, LOXL2, and LINC00886 genes underlying the associations observed in eight of these 28 newly identified risk loci. In addition, we replicated the association for 78 of the 166 previously reported risk variants at P < 0.05 in women of Asian descent using GWAS data. These findings improve our understanding of breast cancer genetics and etiology and extend to Asian populations previous findings from studies of European women.

scholarly journals Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/Cas9-based approach

2018 ◽  
Author(s):  
Benedikt von der Heyde ◽  
Anastasia Emmanouilidou ◽  
Eugenia Mazzaferro ◽  
Silvia Vicenzi ◽  
Ida Höijer ◽  
...  
Keyword(s):  
Heart Rate ◽  
Candidate Genes ◽  
Association Studies ◽  
Meta Analysis ◽  
Automated Analysis ◽  
Zebrafish Embryos ◽  
Genome Wide Association Studies ◽  
Genome Wide

AbstractA meta-analysis of genome-wide association studies (GWAS) identified eight loci that are associated with heart rate variability (HRV), but candidate genes in these loci remain uncharacterized. We developed an image- and CRISPR/Cas9-based pipeline to systematically characterize candidate genes for HRV in live zebrafish embryos. Nine zebrafish orthologues of six human candidate genes were targeted simultaneously in eggs from fish that transgenically express GFP on smooth muscle cells (Tg[acta2:GFP]), to visualize the beating heart. An automated analysis of repeated 30s recordings of beating atria in 381 live, intact zebrafish embryos at 2 and 5 days post-fertilization highlighted genes that influence HRV (hcn4 and si:dkey-65j6.2 [KIAA1755]); heart rate (rgs6 and hcn4); and the risk of sinoatrial pauses and arrests (hcn4). Exposure to 10 or 25µM ivabradine – an open channel blocker of HCNs – for 24h resulted in a dose-dependent higher HRV and lower heart rate at 5 days post-fertilization. Hence, our screen confirmed the role of established genes for heart rate and rhythm (RGS6 and HCN4); showed that ivabradine reduces heart rate and increases HRV in zebrafish embryos, as it does in humans; and highlighted a novel gene that plays a role in HRV (KIAA1755).

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