scholarly journals Recent Advances in Genetic Predisposition of Myasthenia Gravis

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Zoi Zagoriti ◽  
Manousos E. Kambouris ◽  
George P. Patrinos ◽  
Socrates J. Tzartos ◽  
Konstantinos Poulas
Keyword(s):  
Myasthenia Gravis ◽  
Genome Wide Association Study ◽  
Focal Point ◽  
Association Studies ◽  
Age At Onset ◽  
Muscular Weakness ◽  
Genetic Studies ◽  
The Past ◽  
Genome Wide ◽  
Candidate Gene Studies

Myasthenia gravis (MG) is an autoimmune disease mediated by the presence of autoantibodies that bind to components of the neuromuscular junction, causing the symptoms of muscular weakness and fatigability. Like most autoimmune disorders, MG is a multifactorial, noninherited disease, though with an established genetic constituent. The heterogeneity observed in MG perplexes genetic analysis even more, as it occurs in various levels, including diverse autoantigens, thymus histopathology, and age at onset. In this context of distinct subgroups, a plethora of association studies, discussed in this review, have assessed the involvement of various HLA and non-HLA related loci in MG susceptibility, over the past five years. As expected, certain HLA alleles were strongly associated with MG. Many of the non-HLA genes, such asPTPN22andCTLA-4, have been previously studied in MG and other autoimmune diseases and their association with MG has been reevaluated in more cohesive groups of patients. Moreover, novel risk or protective loci have been revealed, as in the case ofTNIP1andFOXP3. Although the majority of these results have been derived from candidate gene studies, the focal point of all recent genetic studies is the first genome-wide association study (GWAS) conducted on early-onset MG patients.

scholarly journals Review: Population Structure in Genetic Studies: Confounding Factors and Mixed Models

2016 ◽  
Author(s):  
Lana S. Martin ◽  
Eleazar Eskin
Keyword(s):  
Population Structure ◽  
Mixed Models ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Laboratory Mouse ◽  
Mouse Strains ◽  
Genetic Studies ◽  
The Past ◽  
Genome Wide ◽  
A Genome

AbstractA genome-wide association study (GWAS) seeks to identify genetic variants that contribute to the development and progression of a specific disease. Over the past 10 years, new approaches using mixed models have emerged to mitigate the deleterious effects of population structure and relatedness in association studies. However, developing GWAS techniques to effectively test for association while correcting for population structure is a computational and statistical challenge. Using laboratory mouse strains as an example, our review characterizes the problem of population structure in association studies and describes how it can cause false positive associations. We then motivate mixed models in the context of unmodeled factors.

Genetics of Intracranial Aneurysms

Stroke ◽  
2021 ◽  
Author(s):  
Mark K. Bakker ◽  
Ynte M. Ruigrok
Keyword(s):  
Genetic Risk ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Association Studies ◽  
Current Status ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
The Past ◽  
Genome Wide ◽  
Family Based ◽  
Severe Type

Rupture of an intracranial aneurysm leads to aneurysmal subarachnoid hemorrhage, a severe type of stroke which is, in part, driven by genetic variation. In the past 10 years, genetic studies of IA have boosted the number of known genetic risk factors and improved our understanding of the disease. In this review, we provide an overview of the current status of the field and highlight the latest findings of family based, sequencing, and genome-wide association studies. We further describe opportunities of genetic analyses for understanding, prevention, and treatment of the disease.

Vasculitis: Decade in Review

2018 ◽  
Vol 15 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Selcan Demir ◽  
Hafize Emine Sönmez ◽  
Seza Özen
Keyword(s):  
Targeted Therapies ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
The Past ◽  
Genome Wide ◽  
New Perspective

Background: In the last decade, we have come to better understand and manage the vasculitides. The classification of vasculitides has been revised. Genome- wide association studies and linkage analyses have been undertaken in hope of better understanding the pathogenesis of vasculitides. Comprehensive genetic studies have highlighted new pathways that may guide us in more targeted therapies. Description of the monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2), Haploinsufficiency of A20 (HA20), have introduced a new perspective to vasculopathies, and introduced alternative treatments for these diseases. Conclusion: In this review, the important discoveries in pathogenesis and consensus treatment recommendations from the past decade will be summarized.

scholarly journals Perspective and a brief overview of genome-wide association studies in moderate to severe asthma

2021 ◽  
Vol 15 (2) ◽  
pp. 52-61
Author(s):  
Md Monirul Hoque
Keyword(s):  
Severe Asthma ◽  
Association Studies ◽  
Chronic Respiratory Disease ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
The Past ◽  
Genome Wide ◽  
Genomic Studies ◽  
The Individual

Asthma is a common chronic respiratory disease that shares phenotypic heritability and shows clusters of symptoms among the relatives. A large number of studies have been conducted to examine the genetic susceptibility of asthma over the past three decades. In the last decade, genome-wide association studies (GWAS) have readdressed the perspective of viewing asthma and have identified some novel genes associated with the susceptibility of asthma. However, few genetic studies have been conducted focusing the moderate to severe asthma, and the molecular targets explain a small proportion of asthma heritability. This review focuses on the principal findings of the genomic studies investigating the genome-wide association of moderate to severe asthma and how it is transitioning the phenotype-based approach towards the fundamental genomic studies. It further illustrates the integrative perspectives aimed towards the translation of the findings in precision medicine. Therefore, a better understanding of asthma pathogenesis would focus the individual at the center of asthma care. Ibrahim Med. Coll. J. 2021; 15(2): 52-61

scholarly journals Genetics of Progressive Supranuclear Palsy: A Review

2020 ◽  
pp. 1-13
Author(s):  
Yafei Wen ◽  
Yafang Zhou ◽  
Bin Jiao ◽  
Lu Shen
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Association Studies ◽  
Age At Onset ◽  
Gene Mutations ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
Genome Wide ◽  
Potential Association ◽  
Rare Genetic Variants ◽  
Vertical Supranuclear Gaze Palsy

Progressive supranuclear palsy (PSP) is an atypical parkinsonism with prominent 4R-tau neuropathology, and the classical clinical phenotype is characterized by vertical supranuclear gaze palsy, unprovoked falls, akinetic-rigid syndrome and cognitive decline. Though PSP is generally regarded as sporadic, there is increasing evidence suggesting that a series of common and rare genetic variants impact on sporadic and familial forms of PSP. To date, more than 10 genes have been reported to show a potential association with PSP. Among these genes, the microtubule-associated protein tau (MAPT) is the risk locus with the strongest effect size on sporadic PSP in the case-control genome-wide association studies (GWAS). Additionally, MAPT mutations are the most common cause of familial PSP while the leucine-rich repeat kinase 2 (LRRK2) is a rare monogenic cause of PSP, and several other gene mutations may mimic the PSP phenotype, like the dynactin subunit 1 (DCTN1). In total, 15 MAPT mutations have been identified in cases with PSP, and the mean age at onset is much earlier than in cases carrying LRRK2 or DCTN1 mutations. GWAS have further identified several risk loci of PSP, proposing molecular pathways related to PSP. The present review focused on genetic studies on PSP and summarized genetic factors of PSP, which may help to elucidate the underlying pathogenesis and provide new perspectives for therapeutic strategies.

scholarly journals Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daniel L. McCartney ◽  
Josine L. Min ◽  
Rebecca C. Richmond ◽  
Ake T. Lu ◽  
Maria K. Sobczyk ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Biological Aging ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Biomarkers Of Aging ◽  
Genome Wide ◽  
Shared Genetic

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

scholarly journals Genetic epidemiology and Mendelian randomization for informing disease therapeutics: conceptual and methodological challenges

2017 ◽  
Author(s):  
Lavinia Paternoster ◽  
Kate Tilling ◽  
George Davey Smith
Keyword(s):  
Genetic Epidemiology ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Disease Treatment ◽  
The Past ◽  
Genome Wide ◽  
Perceived Benefit ◽  
Progression Of Disease ◽  
High Yields

The past decade has been proclaimed as a hugely successful era of gene discovery through the high yields of many genome-wide association studies (GWAS). However, much of the perceived benefit of such discoveries lies in the promise that the identification of genes that influence disease would directly translate into the identification of potential therapeutic targets (1-4), but this has yet to be realised at a level reflecting expectation. One reason for this, we suggest, is that GWAS to date have generally not focused on phenotypes that directly relate to the progression of disease, and thus speak to disease treatment.

scholarly journals Heritability and genome-wide association study of diffusing capacity of the lung

2018 ◽  
Author(s):  
Natalie Terzikhan ◽  
Fangui Sun ◽  
Fien M. Verhamme ◽  
Hieab H.H. Adams ◽  
Daan Loth ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Considerable Proportion ◽  
Genome Wide Association Studies ◽  
Diffusing Capacity ◽  
Human Lung Tissue ◽  
Alveolar Volume ◽  
Genome Wide

AbstractBackgroundAlthough several genome wide association studies (GWAS) have investigated the genetics of pulmonary ventilatory function, little is known about the genetic factors that influence gas exchange.AimTo investigate the heritability of, and genetic variants associated with the diffusing capacity of the lung.MethodsGWAS was performed on diffusing capacity, measured by carbon monoxide uptake (DLCO) and per alveolar volume (DLCO/VA) using the single-breath technique, in 8,372 individuals from two population-based cohort studies, the Rotterdam Study and the Framingham Heart Study. Heritability was estimated in related (n=6,246) and unrelated (n=3,286) individuals.ResultsHeritability of DLCO and DLCO/VA ranged between 23% and 28% in unrelated individuals and between 45% and 49% in related individuals. Meta-analysis identified a genetic variant in GPR126 that is significantly associated with DLCO/VA. Gene expression analysis of GPR126 in human lung tissue revealed a decreased expression in patients with COPD and subjects with decreased DLCO/VA.ConclusionDLCO and DLCO/VA are heritable traits, with a considerable proportion of variance explained by genetics. A functional variant in GPR126 gene region was significantly associated with DLCO/VA. Pulmonary GPR126 expression was decreased in patients with COPD.

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