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.

Genetic Methodologies and Applications

2017 ◽  
Author(s):  
Shaun M. Purcell
Keyword(s):  
Mental Illness ◽  
Genetic Risk ◽  
Genetic Basis ◽  
Common Mental Disorders ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
The Past ◽  
Genome Wide ◽  
Experimental Approaches ◽  
Large Families

Mental illness is highly heritable, yet it has been difficult historically to identify the specific genes that comprise that risk. This difficulty resides in the fact that the genetic risk for all common mental disorders is polygenic, with perhaps hundreds of genetic variations, each of small effect, contributing to the overall risk. Despite these challenges, the field has made dramatic advances over the past decade in beginning to understand the genetic basis of mental illness. This chapter provides an overview of the experimental approaches used, beginning with epidemiology and population genetics to define the heritability of an illness, to classic studies of large families and linkage disequilibrium analysis, to genome-wide investigations including genome-wide association studies (GWAS), exome sequencing, and whole genome sequencing. Increasingly, these genetic advances are being understood within the biological context of disease pathophysiology.

The Association Between Genetic Risk Factors and the Size of Intracranial Aneurysms at Time of Rupture

Neurosurgery ◽  
2013 ◽  
Vol 73 (4) ◽  
pp. 705-708 ◽  
Author(s):  
Rachel Kleinloog ◽  
Femke N.G. van 't Hof ◽  
Franciscus J. Wolters ◽  
Ingeborg Rasing ◽  
Irene C. van der Schaaf ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Intracranial Aneurysms ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genetic Risk Factors ◽  
Genome Wide Association Studies ◽  
Aneurysm Size ◽  
Genome Wide

Abstract BACKGROUND: Genetic risk factors for intracranial aneurysms may influence the size of aneurysms. OBJECTIVE: To assess the association between genetic risk factors and the size of aneurysms at the time of rupture. METHODS: Genotypes of 7 independent single-nucleotide polymorphisms (SNPs) of the 6 genetic risk loci identified in genome-wide association studies of patients with intracranial aneurysms were obtained from 700 Dutch patients with an aneurysmal subarachnoid hemorrhage (1997-2007) previously genotyped in the genome-wide association studies; 255 additional Dutch patients with an aneurysmal subarachnoid hemorrhage (2007-2011) were genotyped for these SNPs. Aneurysms were measured on computerized tomography angiography or digital subtraction angiography. The mean aneurysm size (with standard error) was compared between patients with and without a genetic risk factor by the use of linear regression. The association between SNPs and size was assessed for single SNPs and for the combined effect of SNPs by using a weighted genetic risk score. RESULTS: Single SNPs showed no association with aneurysm size, nor did the genetic risk score. CONCLUSION: The 6 genetic risk loci have no major influence on the size of aneurysms at the time of rupture. Because these risk loci explain no more than 5% of the genetic risk, other genetic factors for intracranial aneurysms may influence aneurysm size and thereby proneness to rupture.

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 Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients

2021 ◽  
Author(s):  
Tiit Nikopensius ◽  
Priit Niibo ◽  
Toomas Haller ◽  
Triin Jagomägi ◽  
Ülle Voog-Oras ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Idiopathic Arthritis ◽  
Autoimmune Diseases ◽  
Genetic Risk ◽  
Association Studies ◽  
Control Sample ◽  
Case Control ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients. Methods We performed genome-wide association analyses in an entire JIA case–control sample (All-JIA) and in a case–control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls. Results We demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10−6), LTBP1 (P = 9,45 × 10−6), and ELMO1 (P = 1,05 × 10−5). In the oligoarticular JIA analysis, the strongest associations were identified at NFIA (P = 5,05 × 10−6), LTBP1 (P = 9,95 × 10−6), MX1 (P = 1,65 × 10−5), and CD200R1 (P = 2,59 × 10−5). Conclusion This study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients. Key Points• Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition.• Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe.• The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci.• The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis.

scholarly journals Genetic Determinants of Paget’s Disease of Bone

2021 ◽  
Author(s):  
Navnit S. Makaram ◽  
Stuart H. Ralston
Keyword(s):  
Genetic Factors ◽  
Association Studies ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Genome Wide Association Studies ◽  
Paget's Disease Of Bone ◽  
Genome Wide ◽  
Family Based

Abstract Purpose of Review To provide an overview of the role of genes and loci that predispose to Paget’s disease of bone and related disorders. Recent Findings Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget’s disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. This brings the total number of genes and loci implicated in PDB to fourteen. Emerging evidence has shown that a number of these genes also predispose to multisystem proteinopathy syndromes where PDB is accompanied by neurodegeneration and myopathy due to the accumulation of abnormal protein aggregates, emphasising the importance of defects in autophagy in the pathogenesis of PDB. Summary Genetic factors play a key role in the pathogenesis of PDB and the studies in this area have identified several genes previously not suspected to play a role in bone metabolism. Genetic testing coupled to targeted therapeutic intervention is being explored as a way of halting disease progression and improving outcome before irreversible skeletal damage has occurred.

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.

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