RIC3 variants are not associated with Parkinson's disease in large European, Latin American, or East Asian cohorts

Kajsa Brolin; Sara Bandres-Ciga; Hampton Leonard; Mary B Makarious; Cornelis Blauwendraat; Ignacio F Mata; Jia Nee Foo; Lasse Pihlstrøm; Maria Swanberg; Ziv Gan-Or; Manuela Mx Tan; International Parkinson's Disease Genomics Consortium

doi:10.1016/j.neurobiolaging.2021.08.009

RIC3 variants are not associated with Parkinson's disease in large European, Latin American, or East Asian cohorts

Neurobiol Aging. 2022 Jan:109:264-268. doi: 10.1016/j.neurobiolaging.2021.08.009. Epub 2021 Aug 21.

Affiliations

¹ Translational Neurogenetics Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address: kajsa.brolin@med.lu.se.
² Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
³ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Center for Alzheimer's and Related Dementias, National Institute on Aging, Bethesda, MD, USA; Data Tecnica International, Glen Echo, MD, USA.
⁴ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK; UCL Movement Disorders Centre, University College London, London, UK.
⁵ Genomic Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
⁶ Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore; Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.
⁷ Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁸ Translational Neurogenetics Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
⁹ Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.

PMID: 34538707
PMCID: PMC9011339
DOI: 10.1016/j.neurobiolaging.2021.08.009

Abstract

Parkinson's disease (PD) is a complex neurodegenerative disorder in which both rare and common genetic variants contribute to disease risk. Multiple genes have been reported to be linked to monogenic PD but these only explain a fraction of the observed familial aggregation. Rare variants in RIC3 have been suggested to be associated with PD in the Indian population. However, replication studies yielded inconsistent results. We further investigate the role of RIC3 variants in PD in European cohorts using individual-level genotyping data from 14,671 PD patients and 17,667 controls, as well as whole-genome sequencing data from 1,615 patients and 961 controls. We also investigated RIC3 using summary statistics from a Latin American cohort of 1,481 individuals, and from a cohort of 31,575 individuals of East Asian ancestry. We did not identify any association between RIC3 and PD in any of the cohorts. However, more studies of rare variants in non-European ancestry populations, in particular South Asian populations, are necessary to further evaluate the world-wide role of RIC3 in PD etiology.

Keywords: Genetics; Parkinson's disease; RIC3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asia, Eastern
Asian People
Cohort Studies
Europe
Female
Genetic Variation / genetics*
Genome-Wide Association Study / methods*
Genotyping Techniques / methods
Hispanic or Latino
Humans
Intracellular Signaling Peptides and Proteins / genetics*
Latin America
Male
Negative Results*
Parkinson Disease / etiology*
Parkinson Disease / genetics*
White People
Whole Genome Sequencing

Substances

Intracellular Signaling Peptides and Proteins
RIC3 protein, human

Grants and funding

Z99 AG999999/ImNIH/Intramural NIH HHS/United States