Genome-Wide Polygenic Score Predicts Large Number of High Risk Individuals in Monogenic Undiagnosed Young Onset Parkinson's Disease Patients from India.

Autor: Kukkle PL; Department of Neurology, Manipal Hospital, Miller Road, Bangalore, 560052, India.; Department of Neurology, Parkinson's Disease and Movement Disorders Clinic, Bangalore, 560010, India.; Department of Neurology, All India Institute of Medical Sciences, Rishikesh, 249201, India., Geetha TS; Research and Diagnostics Department, MedGenome Labs Pvt Ltd, Bangalore, 560099, India., Chaudhary R; Research Department, MedGenome Inc., 348 Hatch Drive, Foster City, CA, 94404, USA., Sathirapongsasuti JF; Research Department, MedGenome Inc., 348 Hatch Drive, Foster City, CA, 94404, USA., Goyal V; Department of Neurology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110608, India.; Department of Neurology, Medanta Hospital, New Delhi, 110047, India.; Department of Neurology, Medanta, The Medicity, Gurgaon, 122006, India., Kandadai RM; Department of Neurology, Nizams Institute of Medical Sciences (NIMS), Hyderabad, 500082, India., Kumar H; Department of Neurology, Institute of Neurosciences Kolkata, Kolkata, 700007, India., Borgohain R; Department of Neurology, Nizams Institute of Medical Sciences (NIMS), Hyderabad, 500082, India., Mukherjee A; Department of Neurology, Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata, 700020, India., Oliver M; Research and Diagnostics Department, MedGenome Labs Pvt Ltd, Bangalore, 560099, India., Sunil M; Research and Diagnostics Department, MedGenome Labs Pvt Ltd, Bangalore, 560099, India., Mootor MFE; Research and Diagnostics Department, MedGenome Labs Pvt Ltd, Bangalore, 560099, India., Kapil S; Research and Diagnostics Department, MedGenome Labs Pvt Ltd, Bangalore, 560099, India., Mandloi N; Research and Diagnostics Department, MedGenome Labs Pvt Ltd, Bangalore, 560099, India., Wadia PM; Department of Neurology, Jaslok Hospital and Research Centre, Mumbai, 400026, India., Yadav R; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, 560029, India., Desai S; Department of Neurology, Shree Krishna Hospital and Pramukhswami Medical College, Bhaikaka University, Karamsad, 388325, India., Kumar N; Department of Neurology, All India Institute of Medical Sciences, Rishikesh, 249201, India., Biswas A; Department of Neurology, Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata, 700020, India., Pal PK; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, 560029, India., Muthane UB; Department of Neurology, Parkinson and Ageing Research Foundation, Bangalore, 560095, India., Das SK; Department of Neurology, Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata, 700020, India., Sakthivel Murugan SM; Research and Diagnostics Department, MedGenome Labs Pvt Ltd, Bangalore, 560099, India., Peterson AS; Research Department, MedGenome Inc., 348 Hatch Drive, Foster City, CA, 94404, USA., Stawiski EW; Research Department, MedGenome Inc., 348 Hatch Drive, Foster City, CA, 94404, USA., Seshagiri S; GenomeAsia 100K Foundation, Foster City, USA., Gupta R; Research and Diagnostics Department, MedGenome Labs Pvt Ltd, Bangalore, 560099, India., Ramprasad VL; Research and Diagnostics Department, MedGenome Labs Pvt Ltd, Bangalore, 560099, India., Prai PRAOI; Hyderabad, 500084, India.
Jazyk: angličtina
Zdroj: Advanced biology [Adv Biol (Weinh)] 2022 Nov; Vol. 6 (11), pp. e2101326. Date of Electronic Publication: 2022 Jul 10.
DOI: 10.1002/adbi.202101326
Abstrakt: Parkinson's disease (PD) is a genetically heterogeneous neurodegenerative disease with poorly defined environmental influences. Genomic studies of PD patients have identified disease-relevant monogenic genes, rare variants of significance, and polygenic risk-associated variants. In this study, whole genome sequencing data from 90 young onset Parkinson's disease (YOPD) individuals are analyzed for both monogenic and polygenic risk. The genetic variant analysis identifies pathogenic/likely pathogenic variants in eight of the 90 individuals (8.8%). It includes large homozygous coding exon deletions in PRKN and SNV/InDels in VPS13C, PLA2G6, PINK1, SYNJ1, and GCH1. Eleven rare heterozygous GBA coding variants are also identified in 13 (14.4%) individuals. In 34 (56.6%) individuals, one or more variants of uncertain significance (VUS) in PD/PD-relevant genes are observed. Though YOPD patients with a prioritized pathogenic variant show a low polygenic risk score (PRS), patients with prioritized VUS or no significant rare variants show an increased PRS odds ratio for PD. This study suggests that both significant rare variants and polygenic risk from common variants together may contribute to the genesis of PD. Further validation using a larger cohort of patients will confirm the interplay between monogenic and polygenic variants and their use in routine genetic PD diagnosis and risk assessment.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: