Dataset Information

Assessment of Parkinson's disease risk loci in Greece.

ABSTRACT: Genome-wide association studies (GWAS) have been shown to be a powerful approach to identify risk loci for neurodegenerative diseases. Recent GWAS in Parkinson's disease (PD) have been successful in identifying numerous risk variants pointing to novel pathways potentially implicated in the pathogenesis of PD. Contributing to these GWAS efforts, we performed genotyping of previously identified risk alleles in PD patients and control subjects from Greece. We showed that previously published risk profiles for Northern European and American populations are also applicable to the Greek population. In addition, although our study was largely underpowered to detect individual associations, we replicated 5 of 32 previously published risk variants with nominal p values <0.05. Genome-wide complex trait analysis revealed that known risk loci explain disease risk in 1.27% of Greek PD patients. Collectively, these results indicate that there is likely a substantial genetic component to PD in Greece, similarly to other worldwide populations, that remains to be discovered.

SUBMITTER: Kara E

PROVIDER: S-EPMC3830580 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Assessment of Parkinson's disease risk loci in Greece.

Kara Eleanna E Xiromerisiou Georgia G Spanaki Cleanthe C Bozi Maria M Koutsis Georgios G Panas Marios M Dardiotis Efthimios E Ralli Styliani S Bras Jose J Letson Christopher C Edsall Connor C Pliner Hannah H Arepalli Sampath S Kalinderi Kallirhoe K Fidani Liana L Bostantjopoulou Sevasti S Keller Margaux F MF Wood Nicholas W NW Hardy John J Houlden Henry H Stefanis Leonidas L Plaitakis Andreas A Hernandez Dena D Hadjigeorgiou Georgios M GM Nalls Mike A MA Singleton Andrew B AB

Neurobiology of aging 20130927 2

Genome-wide association studies (GWAS) have been shown to be a powerful approach to identify risk loci for neurodegenerative diseases. Recent GWAS in Parkinson's disease (PD) have been successful in identifying numerous risk variants pointing to novel pathways potentially implicated in the pathogenesis of PD. Contributing to these GWAS efforts, we performed genotyping of previously identified risk alleles in PD patients and control subjects from Greece. We showed that previously published risk p ...[more]

PMID: 24080174

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Project description:BackgroundGenome-wide association studies (GWAS) have indicated moderate genetic overlap between Alzheimer's disease (AD) and related dementias (ADRD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), neurodegenerative disorders traditionally considered etiologically distinct. However, the specific genetic variants and loci underlying this overlap remain almost entirely unknown.MethodsWe leveraged state-of-the-art GWAS for ADRD, PD, and ALS. For each pair of disorders, we examined each of the GWAS hits for one disorder and tested whether they were also significant for the other disorder, applying Bonferroni correction for the number of variants tested. This approach rigorously controls the family-wise error rate for both disorders, analogously to genome-wide significance.ResultsEleven loci with GWAS hits for one disorder were also associated with one or both of the other disorders: one with all three disorders (the MAPT/KANSL1 locus), five with ADRD and PD (near LCORL, CLU, SETD1A/KAT8, WWOX, and GRN), three with ADRD and ALS (near GPX3, HS3ST5/HDAC2/MARCKS, and TSPOAP1), and two with PD and ALS (near GAK/TMEM175 and NEK1). Two of these loci (LCORL and NEK1) were associated with an increased risk of one disorder but decreased risk of another. Colocalization analysis supported a shared causal variant between ADRD and PD at the CLU, WWOX, and LCORL loci, between ADRD and ALS at the TSPOAP1 locus, and between PD and ALS at the NEK1 and GAK/TMEM175 loci. To address the concern that ADRD is an imperfect proxy for AD and that the ADRD and PD GWAS have overlapping participants (nearly all of which are from the UK Biobank), we confirmed that all our ADRD associations had nearly identical odds ratios in an AD GWAS that excluded the UK Biobank, and all but one remained nominally significant (p < 0.05) for AD.ConclusionsIn one of the most comprehensive investigations to date of pleiotropy between neurodegenerative disorders, we identify eleven genetic risk loci shared among ADRD, PD, and ALS. These loci support lysosomal/autophagic dysfunction (GAK/TMEM175, GRN, KANSL1), neuroinflammation/immunity (TSPOAP1), oxidative stress (GPX3, KANSL1), and the DNA damage response (NEK1) as transdiagnostic processes underlying multiple neurodegenerative disorders.

Project description:Falls are a major concern for people with Parkinson's disease (PwPD), but accurately assessing real-world fall risk beyond the clinic is challenging. Contemporary technologies could enable the capture of objective and high-resolution data to better inform fall risk through measurement of everyday factors (e.g., obstacles) that contribute to falls. Wearable inertial measurement units (IMUs) capture objective high-resolution walking/gait data in all environments but are limited by not providing absolute clarity on contextual information (i.e., obstacles) that could greatly influence how gait is interpreted. Video-based data could compliment IMU-based data for a comprehensive free-living fall risk assessment. The objective of this study was twofold. First, pilot work was conducted to propose a novel artificial intelligence (AI) algorithm for use with wearable video-based eye-tracking glasses to compliment IMU gait data in order to better inform free-living fall risk in PwPD. The suggested approach (based on a fine-tuned You Only Look Once version 8 (YOLOv8) object detection algorithm) can accurately detect and contextualize objects (mAP50 = 0.81) in the environment while also providing insights into where the PwPD is looking, which could better inform fall risk. Second, we investigated the perceptions of PwPD via a focus group discussion regarding the adoption of video technologies and AI during their everyday lives to better inform their own fall risk. This second aspect of the study is important as, traditionally, there may be clinical and patient apprehension due to ethical and privacy concerns on the use of wearable cameras to capture real-world video. Thematic content analysis was used to analyse transcripts and develop core themes and categories. Here, PwPD agreed on ergonomically designed wearable video-based glasses as an optimal mode of video data capture, ensuring discreteness and negating any public stigma on the use of research-style equipment. PwPD also emphasized the need for control in AI-assisted data processing to uphold privacy, which could overcome concerns with the adoption of video to better inform IMU-based gait and free-living fall risk. Contemporary technologies (wearable video glasses and AI) can provide a holistic approach to fall risk that PwPD recognise as helpful and safe to use.

Dataset Information

Assessment of Parkinson's disease risk loci in Greece.

Publications

Assessment of Parkinson's disease risk loci in Greece.

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