An emerging role for LRRK2 in the immune system

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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Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections

10.1101/073056 ◽

2016 ◽

Cited By ~ 1

Author(s):

Chao Tian ◽

Bethann S. Hromatka ◽

Amy K Kiefer ◽

Nicholas Eriksson ◽

Joyce Y Tung ◽

...

Keyword(s):

Fine Mapping ◽

Association Studies ◽

Genome Wide Association ◽

European Ancestry ◽

Multiple Infections ◽

Genome Wide Association Studies ◽

Missense Mutations ◽

Genome Wide ◽

Tract Infections ◽

Common Infections

ABSTRACTWe performed 23 genome-wide association studies for common infections, including chickenpox, shingles, cold sores, mononucleosis, mumps, hepatitis B, plantar warts, positive tuberculosis test results, strep throat, scarlet fever, pneumonia, bacterial meningitis, yeast infections, urinary tract infections, tonsillectomy, childhood ear infections, myringotomy, measles, hepatitis A, rheumatic fever, common colds, rubella and chronic sinus infection, in more than 200,000 individuals of European ancestry. For the first time, genome-wide significant associations (P< 5 × 10−8) were identified for many common infections. The associations were mapped to genes with key roles in acquired and innate immunity(HLA, IFNA21, FUT2, ST3GAL4, ABO, IFNL4, LCE3E, DSG1, LTBR, MTMR3, TNFRSF13B, TNFSF13B, NFKB1, CD40) and in regulation of embryonic developmental process(TBX1, FGF, FOXA1 and FOXN1).Several missense mutations were also identified (inLCE5A, DSG1, FUT2, TBX1, CDHR3, PLG, TNFRSF13B, FOXA1, SH2B3, ST5andFOXN1). Missense mutations inFUT2andTBX1were implicated in multiple infections. We applied fine-mapping analysis to dissect associations in the human leukocyte antigen region, which suggested important roles of specific amino acid polymorphisms in the antigen-binding clefts. Our findings provide an important step toward dissecting the host genetic architecture of response to common infections.

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Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for theCYP4F3locus

Molecular Carcinogenesis ◽

10.1002/mc.22622 ◽

2017 ◽

Vol 56 (6) ◽

pp. 1663-1672 ◽

Cited By ~ 8

Author(s):

Jieyun Yin ◽

Hongliang Liu ◽

Zhensheng Liu ◽

Kouros Owzar ◽

Younghun Han ◽

...

Keyword(s):

Lung Cancer ◽

Pathway Analysis ◽

Potential Role ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide

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LRRK2 and autophagy: a common pathway for disease

Biochemical Society Transactions ◽

10.1042/bst20120126 ◽

2012 ◽

Vol 40 (5) ◽

pp. 1147-1151 ◽

Cited By ~ 13

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.

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