Evaluating ANO6 as a Parkinson’s disease candidate gene: a human genetic investigation of common and rare variant associations
ABSTRACT ANO6 (TMEM16F) , a Ca 2 □-activated lipid scramblase and ion channel, has been implicated in α-synuclein secretion and propagation, a hallmark of Parkinson’s disease (PD). To evaluate whether genetic variation in ANO6 contributes to PD risk, we analyzed common and rare variants across large-scale datasets. Relying on genome-wide association study (GWAS) summary statistics from 63,555 PD cases, 17,700 proxy cases, and 1.7 million controls, we identified seven noncoding common variants within ANO6 that reached genome-wide significance, but these signals were driven by linkage disequilibrium (LD) with the nearby LRRK2 p.G2019S variant. We further tested rare variant burden in 4,879 PD cases and 65,279 controls. Rare variant burden analysis showed significant enrichment only when all rare variants were aggregated (meta-analysis P FDR = 0.02), with no signal detected in functional categories. Overall, human genetic data does not support an important role for ANO6 in PD.
Authors
- Konstantin A. Senkevich (ORCID: https://orcid.org/0000-0003-3407-5716)
- Hampton L. Leonard (ORCID: https://orcid.org/0000-0003-2390-8110)
- Sitki Cem Parlar (ORCID: https://orcid.org/0009-0003-9026-114X)
- Lang Liu (ORCID: https://orcid.org/0000-0002-0348-2258)
- Ziv Gan‐Or (ORCID: https://orcid.org/0000-0003-0332-234X)
- Meron Teferra (ORCID: https://orcid.org/0009-0007-6033-8475)
- the Global Parkinson’s Genetic Program (GP2)
Institutions
- Montreal Neurological Institute and Hospital (CA)
- McGill University Health Centre (CA)
- McGill University (CA)
Publication Details
- Journal
- Parkinsonism & Related Disorders
- Published
- 2026-11-01
- DOI
- https://doi.org/10.1016/j.parkreldis.2026.109027
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Foundation for the National Institutes of Health
- U.S. Department of Health and Human Services
- Michael J. Fox Foundation for Parkinson's Research
- Bristol-Myers Squibb
- Pfizer
- GlaxoSmithKline
- Sanofi
- Yale University
- Celgene
- McGill University
- Verily Life Sciences
- Canada First Research Excellence Fund
- Alliance de recherche numérique du Canada
- National Institutes of Health
- National Institute on Aging
- National Institute of Neurological Disorders and Stroke