Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis

2018 ◽  
Vol 78 (3) ◽  
pp. 355-364 ◽  
Author(s):  
Adrià Aterido ◽  
Juan D Cañete ◽  
Jesús Tornero ◽  
Carlos Ferrándiz ◽  
José Antonio Pinto ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Psoriatic Arthritis ◽  
Drug Targets ◽  
Genome Wide Association Study ◽  
New Drugs ◽  
Genetic Associations ◽  
Metabolism Pathway ◽  
A Genome ◽  
Disease Specific ◽  
Pathway Level

ObjectivePsoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.MethodsWe performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case–control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA.ResultsWe identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs.ConclusionThese findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

scholarly journals Genetic variation in recombination rate in the pig

2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Martin Johnsson ◽  
Andrew Whalen ◽  
Roger Ros-Freixedes ◽  
Gregor Gorjanc ◽  
Ching-Yi Chen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Recombination Rate ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Genetic Material ◽  
A Genome ◽  
Pig Genome ◽  
Genetic Length ◽  
Trait Locus ◽  
Genomic Regions

Abstract Background Meiotic recombination results in the exchange of genetic material between homologous chromosomes. Recombination rate varies between different parts of the genome, between individuals, and is influenced by genetics. In this paper, we assessed the genetic variation in recombination rate along the genome and between individuals in the pig using multilocus iterative peeling on 150,000 individuals across nine genotyped pedigrees. We used these data to estimate the heritability of recombination and perform a genome-wide association study of recombination in the pig. Results Our results confirmed known features of the recombination landscape of the pig genome, including differences in genetic length of chromosomes and marked sex differences. The recombination landscape was repeatable between lines, but at the same time, there were differences in average autosome-wide recombination rate between lines. The heritability of autosome-wide recombination rate was low but not zero (on average 0.07 for females and 0.05 for males). We found six genomic regions that are associated with recombination rate, among which five harbour known candidate genes involved in recombination: RNF212, SHOC1, SYCP2, MSH4 and HFM1. Conclusions Our results on the variation in recombination rate in the pig genome agree with those reported for other vertebrates, with a low but nonzero heritability, and the identification of a major quantitative trait locus for recombination rate that is homologous to that detected in several other species. This work also highlights the utility of using large-scale livestock data to understand biological processes.

scholarly journals Genetic variation associated with chromosomal aberration frequency: A genome-wide association study

2018 ◽  
Vol 60 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Yasmeen Niazi ◽  
Hauke Thomsen ◽  
Bozena Smolkova ◽  
Ludmila Vodickova ◽  
Sona Vodenkova ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Association Study ◽  
Chromosomal Aberration ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Aberration Frequency ◽  
Genome Wide ◽  
A Genome

scholarly journals GP.01 Childhood obesity and multiple sclerosis susceptibility: a Mendelian randomization study

2019 ◽  
Vol 46 (s1) ◽  
pp. S6 ◽  
Author(s):  
A Harroud ◽  
RE Mitchell ◽  
JA Morris ◽  
V Forgetta ◽  
SJ Sawcer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Childhood Obesity ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Significant Heterogeneity ◽  
Genetic Associations ◽  
Standard Deviation Increase ◽  
A Genome ◽  
The Individual

Background: Observational studies have reported an association between childhood obesity and a higher risk of multiple sclerosis (MS). However, the difficulties to fully account for confounding and long recall periods make causal inference from these studies challenging. The objective of this study was to assess the contribution of childhood obesity to the development of MS through Mendelian randomization, which uses genetic associations to minimize the risk of confounding. Methods: We selected 23 independent genetic variants strongly associated with childhood body mass index (BMI) in a genome-wide association study (GWAS) which included 47,541 children. The corresponding effects of these variants on risk of MS were obtained from a GWAS of 14,802 MS cases and 26,703 controls. Standard two-sample Mendelian randomization methods were performed, with additional sensitivity analyses to assess the likelihood of bias from genetic pleiotropy. Results: The inverse-variance weighted MR analysis revealed that one standard deviation increase in childhood BMI increased odds of MS by 26% (odds ratio=1.26, 95% confidence interval 1.10-1.45, p=0.001). There was no significant heterogeneity across the individual estimates. Sensitivity analyses were consistent with the main findings and provided no evidence of pleiotropy. Conclusions: This study provides genetic support of a role for increased childhood BMI in the development of MS.

scholarly journals A genome-wide association study demonstrates significant genetic variation for fracture risk in Thoroughbred racehorses

BMC Genomics ◽  
2014 ◽  
Vol 15 (1) ◽  
pp. 147 ◽  
Author(s):  
Sarah C Blott ◽  
June E Swinburne ◽  
Charlene Sibbons ◽  
Laura Y Fox-Clipsham ◽  
Maud Helwegen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Fracture Risk ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Thoroughbred Racehorses ◽  
Genome Wide ◽  
A Genome

scholarly journals Genetic studies of accelerometer-based sleep measures in 85,670 individuals yield new insights into human sleep behaviour

2018 ◽  
Author(s):  
Samuel E. Jones ◽  
Vincent T. van Hees ◽  
Diego R. Mazzotti ◽  
Pedro Marques-Vidal ◽  
Séverine Sabia ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Sleep Duration ◽  
Genome Wide Association Study ◽  
Missense Variant ◽  
Causal Variant ◽  
Self Report ◽  
Accelerometer Data ◽  
Genetic Associations ◽  
A Genome ◽  
The Uk

ABSTRACTSleep is an essential human function but its regulation is poorly understood. Identifying genetic variants associated with quality, quantity and timing of sleep will provide biological insights into the regulation of sleep and potential links with disease. Using accelerometer data from 85,670 individuals in the UK Biobank, we performed a genome-wide association study of 8 accelerometer-derived sleep traits, 5 of which are not accessible through self-report alone. We identified 47 genetic associations across the sleep traits (P<5×10-8) and replicated our findings in 5,819 individuals from 3 independent studies. These included 26 novel associations for sleep quality and 10 for nocturnal sleep duration. The majority of newly identified variants were associated with a single sleep trait, except for variants previously associated with restless legs syndrome that were associated with multiple sleep traits. Of the new associated and replicated sleep duration loci, we were able to fine-map a missense variant (p.Tyr727Cys) in PDE11A, a dual-specificity 3’,5’-cyclic nucleotide phosphodiesterase expressed in the hippocampus, as the likely causal variant. As a group, sleep quality loci were enriched for serotonin processing genes and all sleep traits were enriched for cerebellar-expressed genes. These findings provide new biological insights into sleep characteristics.

scholarly journals Genetic Associations with Subjective Well-Being Also Implicate Depression and Neuroticism

2015 ◽  
Author(s):  
Aysu Okbay ◽  
Bart M. L. Baselmans ◽  
Jan-Emmanuel De Neve ◽  
Patrick Turley ◽  
Michel G. Nivard ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Genome Wide Association Study ◽  
Well Being ◽  
Genome Wide Association ◽  
Subjective Well Being ◽  
Genetic Associations ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Significance

We conducted a genome-wide association study of subjective well-being (SWB) in 298,420 individuals. We also performed auxiliary analyses of depressive symptoms ("DS";N= 161,460) and neuroticism (N= 170,910), both of which have a substantial genetic correlation with SWB (ρ≈-0.8). We identify three SNPs associated with SWB at genome-wide significance. Two of them are significantly associated with DS in an independent sample. In our auxiliary analyses, we identify 13 additional genome-wide-significant associations: two with DS and eleven with neuroticism, including two inversion polymorphisms. Across our phenotypes, loci regulating expression in central nervous system and adrenal/pancreas tissues are enriched. The discovery of genetic loci associated with the three phenotypes we study has proven elusive; our findings illustrate the payoffs from studying them jointly.

scholarly journals New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries

2018 ◽  
Author(s):  
Nick Shrine ◽  
Anna L Guyatt ◽  
A Mesut Erzurumluoglu ◽  
Victoria E Jackson ◽  
Brian D Hobbs ◽  
...  
Keyword(s):  
Lung Function ◽  
Drug Targets ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
European Ancestry ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
A Genome ◽  
Disease Associations ◽  
Never Smokers

AbstractReduced lung function predicts mortality and is key to the diagnosis of COPD. In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, one-half of which are new. In combination these variants strongly predict COPD in deeply-phenotyped patient populations. Furthermore, the combined effect of these variants showed generalisability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 1000-1000 ◽  
Author(s):  
B. P. Schneider ◽  
L. Li ◽  
K. Miller ◽  
D. Flockhart ◽  
M. Radovich ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genetic Associations ◽  
Genome Wide ◽  
A Genome
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