LRRK2 and autophagy: a common pathway for disease

2012 ◽  
Vol 40 (5) ◽  
pp. 1147-1151 ◽  
Author(s):  
Claudia Manzoni
Keyword(s):  
Human Disease ◽  
Association Studies ◽  
Open Reading Frame ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Leucine Rich Repeat ◽  
Common Pathway ◽  
Reading Frame ◽  
Genome Wide ◽  
Lrrk2 Gene

LRRK2 (leucine-rich repeat kinase 2) is an enzyme implicated in human disease, containing kinase and GTPase functions within the same multidomain open reading frame. Dominant mutations in the LRRK2 gene are the most common cause of familial PD (Parkinson's disease). Additionally, in genome-wide association studies, the LRRK2 locus has been linked to risk of PD, Crohn's disease and leprosy, and LRRK2 has also been linked with cancer. Despite its association with human disease, very little is known about its pathophysiology. Recent reports suggest a functional association between LRRK2 and autophagy. Implications of this set of data for our understanding of LRRK2′s role in physiology and disease are discussed in the present paper.

scholarly journals The predictive power of the microbiome exceeds that of genome-wide association studies in the discrimination of complex human disease

2020 ◽  
Author(s):  
Braden T Tierney ◽  
Yixuan He ◽  
George M Church ◽  
Eran Segal ◽  
Aleksandar D Kostic ◽  
...  
Keyword(s):  
Association Study ◽  
Human Disease ◽  
Genome Wide Association Study ◽  
Human Genetics ◽  
Association Studies ◽  
Human Microbiome ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Common Variants ◽  
Genome Wide

AbstractOver the past decade, studies of the human genome and microbiome have deepened our understanding of the connections between human genes, environments, microbes, and disease. For example, the sheer number of indicators of the microbiome and human genetic common variants associated with disease has been immense, but clinical utility has been elusive. Here, we compared the predictive capabilities of the human microbiome versus human genomic common variants across 13 common diseases. We concluded that microbiomic indicators outperform human genetics in predicting host phenotype (overall Microbiome-Association-Study [MAS] area under the curve [AUC] = 0.79 [SE = 0.03], overall Genome-Wide-Association-Study [GWAS] AUC = 0.67 [SE = 0.02]). Our results, while preliminary and focused on a subset of the totality of disease, demonstrate the relative predictive ability of the microbiome, indicating that it may outperform human genetics in discriminating human disease cases and controls. They additionally motivate the need for population-level microbiome sequencing resources, akin to the UK Biobank, to further improve and reproduce metagenomic models of disease.

scholarly journals The impact of genome-wide association studies on biomedical research publications

2017 ◽  
Author(s):  
Travis J. Struck ◽  
Brian K. Mannakee ◽  
Ryan N. Gutenkunst
Keyword(s):  
Biomedical Research ◽  
Human Disease ◽  
Association Studies ◽  
Genome Wide Association ◽  
Disease Genes ◽  
Genome Wide Association Studies ◽  
Complex Human Disease ◽  
The Past ◽  
Research Publications ◽  
Genome Wide

AbstractThe past decade has seen major investment in genome-wide association studies (GWAS), with the goal of identifying and motivating research on novel genes involved in complex human disease. To assess whether this goal is being met, we quantified the effect of GWAS on the overall distribution of biomedical research publications and on the subsequent publication history of genes newly associated with complex disease. We found that the historical skew of publications toward genes involved in Mendelian disease has not changed since the advent of GWAS. Genes newly implicated by GWAS in complex disease do experience additional publications compared to control genes, and they are more likely to become exceptionally studied. But the magnitude of both effects has declined dramatically over the past decade. Our results suggest that reforms to encourage follow-up studies may be needed for GWAS to most successfully guide biomedical research toward the molecular mechanisms underlying complex human disease.Author summaryOver the past decade, thousands of genome-wide association studies (GWAS) have been performed to link genetic variation with complex human disease. A major goal of such studies is to identify novel disease genes, so they can be further studied. We tested whether this goal is being met, by studying patterns of scientific research publications on human genes. We found that publications are still concentrated on genes involved in simple Mendelian disease, even after the advent of GWAS. Compared to other genes, disease genes discovered by GWAS do experience additional publications, but that effect has declined dramatically since GWAS were first performed. Our results suggest that the ability of GWAS to stimulate research into novel disease genes is declining. To realize the full potential of GWAS to reveal the molecular mechanisms driving human disease, this decline and the reasons for it must be understood, so that it can be reversed.

Genome-wide Association Studies and Human Disease

JAMA ◽  
2009 ◽  
Vol 302 (18) ◽  
pp. 2028 ◽  
Author(s):  
Peter M. Visscher ◽  
Grant W. Montgomery
Keyword(s):  
Human Disease ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals NELL-1 in Genome-Wide Association Studies across Human Disease

2021 ◽  
Author(s):  
Xu Cheng ◽  
Jiayu Shi ◽  
Zhonglin Jia ◽  
Pin Ha ◽  
Chia Soo ◽  
...  
Keyword(s):  
Human Disease ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals An emerging role for LRRK2 in the immune system

2012 ◽  
Vol 40 (5) ◽  
pp. 1134-1139 ◽  
Author(s):  
Nicolas Dzamko ◽  
Glenda M. Halliday
Keyword(s):  
Risk Factor ◽  
Immune Cells ◽  
Potential Role ◽  
Autosomal Dominant ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Missense Mutations ◽  
Leucine Rich Repeat ◽  
Genome Wide

Missense mutations in LRRK2 (leucine-rich repeat kinase 2) contribute significantly to autosomal dominant PD (Parkinson's disease). Genome-wide association studies have suggested further that mutations in LRRK2 comprise a risk factor for sporadic PD. How LRRK2 contributes to PD, however, is largely unknown. Recent work has shown that LRRK2 is highly expressed in tissue and circulating immune cells and is suggestive of a potential role for LRRK2 in innate immunity. These studies and their potential implications for PD are discussed in the present paper.

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