The Genetic Drivers of Juvenile, Young, and Early-Onset Parkinson's Disease in India.

Autor: Andrews SV; Denali Therapeutics, South San Francisco, California, USA., Kukkle PL; Manipal Hospital, Bangalore, India.; Parkinson's Disease and Movement Disorders Clinic, Bangalore, India., Menon R; MedGenome Labs Ltd, Bangalore, India., Geetha TS; MedGenome Labs Ltd, Bangalore, India., Goyal V; All India Institute of Medical Sciences (AIIMS), New Delhi, India.; Medanta Hospital, New Delhi, India.; Medanta, The Medicity, Gurgaon, India., Kandadai RM; Nizams Institute of Medical Sciences (NIMS), Hyderabad, India.; Citi Neuro Centre, Hyderabad, India., Kumar H; Institute of Neurosciences Kolkata, Kolkata, India., Borgohain R; Nizams Institute of Medical Sciences (NIMS), Hyderabad, India.; Citi Neuro Centre, Hyderabad, India., Mukherjee A; Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata, India., Wadia PM; Jaslok Hospital and Research Centre, Mumbai, India., Yadav R; National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India., Desai S; Department of Neurology, Shree Krishna Hospital and Pramukhaswami Medical College, Bhaikaka University, Anand, India., Kumar N; All India Institute of Medical Sciences, Rishikesh, India.; All India Institute of Medical Sciences, Bibinagar (Hyderabad Metropolitan Region), Bibinagar, India., Joshi D; Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India., Murugan S; MedGenome Labs Ltd, Bangalore, India., Biswas A; Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata, India., Pal PK; National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India., Oliver M; MedGenome Labs Ltd, Bangalore, India., Nair S; MedGenome Labs Ltd, Bangalore, India., Kayalvizhi A; MedGenome Labs Ltd, Bangalore, India., Samson PL; MedGenome Labs Ltd, Bangalore, India., Deshmukh M; MedGenome Labs Ltd, Bangalore, India., Bassi A; MedGenome Labs Ltd, Bangalore, India., Sandeep C; MedGenome Labs Ltd, Bangalore, India., Mandloi N; MedGenome Labs Ltd, Bangalore, India., Davis OB; Denali Therapeutics, South San Francisco, California, USA., Roberts MA; Denali Therapeutics, South San Francisco, California, USA., Leto DE; Denali Therapeutics, South San Francisco, California, USA., Henry AG; Denali Therapeutics, South San Francisco, California, USA., Di Paolo G; Denali Therapeutics, South San Francisco, California, USA., Muthane U; Parkinson and Ageing Research Foundation, Bangalore, India., Das SK; Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata, India., Peterson AS; MedGenome Labs Ltd, Bangalore, India., Sandmann T; Denali Therapeutics, South San Francisco, California, USA., Gupta R; MedGenome Labs Ltd, Bangalore, India., Ramprasad VL; MedGenome Labs Ltd, Bangalore, India.
Jazyk: angličtina
Zdroj: Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2024 Feb; Vol. 39 (2), pp. 339-349. Date of Electronic Publication: 2023 Nov 28.
DOI: 10.1002/mds.29676
Abstrakt: Background: Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome-wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority of these studies were focused.
Objective: The aim was to identify genetic risk factors for PD in a South Asian population.
Methods: A total of 674 PD subjects predominantly with age of onset (AoO) ≤50 years (encompassing juvenile, young, or early-onset PD) were recruited from 10 specialty movement disorder centers across India over a 2-year period; 1376 control subjects were selected from the reference population GenomeAsia, Phase 2. We performed various case-only and case-control genetic analyses for PD diagnosis and AoO.
Results: A genome-wide significant signal for PD diagnosis was identified in the SNCA region, strongly colocalizing with SNCA region signal from European PD GWAS. PD cases with pathogenic mutations in PD genes exhibited, on average, lower PD polygenic risk scores than PD cases lacking any PD gene mutations. Gene burden studies of rare, predicted deleterious variants identified BSN, encoding the presynaptic protein Bassoon that has been previously associated with neurodegenerative disease.
Conclusions: This study constitutes the largest genetic investigation of PD in a South Asian population to date. Future work should seek to expand sample numbers in this population to enable improved statistical power to detect PD genes in this understudied group. © 2023 Denali Therapeutics and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
(© 2023 Denali Therapeutics and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Databáze: MEDLINE
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