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Abstract Details

Rare TMEM230 Variants are Potentially Associated With Early Onset Parkinson's Disease
Movement Disorders
P3 - Poster Session 3 (5:30 PM-6:30 PM)
5-013

In the current study, we assessed whether rare variants in TMEM230 and LRP10 are associated with Parkinson’s disease (PD) and early onset PD (EOPD,≤50 years).
Several studies reported an association between PD and variants in TMEM230 and LRP10. However, this association remains controversial, as limited evidence supports the overrepresentation of rare variants in these genes in PD.
To study the association of rare variants in LRP10 and TMEM230 with PD, we performed an analysis in four cohorts sequenced at McGill with a total of 3,302 PD patients and 1,938 controls. Targeted sequencing was performed by molecular inversion probes. We then analyzed whole-genome and whole-exome sequencing data from two publicly available cohorts, the Accelerating Medicines Partnership-PD cohort (AMP-PD) and UK-Biobank(UKBB) with a total of 2,943 PD cases and 18,486 controls. Standard quality control was performed on individual and variant levels for each cohort separately. For the analysis of rare variants (minor allele frequency<1%), we applied an optimized sequence Kernel association test (SKAT-O). Meta-analysis of SKAT-O results between cohorts sequenced at McGill with AMP-PD and UKBB cohorts was done using the MetaSKAT package in R.
In a meta-analysis of all six cohorts, we found an association between rare non-synonymous and variants with high Combined annotation-dependent depletion score(>20) in TMEM230 and EOPD with p=0.002 and p=0.007, respectively (threshold after Bonferroni correction p=0.003). We did not find any role of rare TMEM230 variants in PD when studied patients of all ages together. We also did not find any association between LRP10 variants and PD.
Rare TMEM230 variants are associated with EOPD in our data. These results should be considered with caution as their statistical significance is borderline. Our results do not support an association of rare LRP10 variants with PD. However, we cannot exclude the role of very rare pathogenic LRP10 mutations in PD.
Authors/Disclosures
Konstantin Senkevich, MD
PRESENTER 		The institution of Dr. Senkevich has received research support from MJFF. Dr. Senkevich has received research support from HBHL. Dr. Senkevich has received research support from FRQS.
No disclosure on file
Uladzislau Rudakou Mr. Rudakou has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Stanley Fahn, MD, FAAN Dr. Fahn has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Stoparkinson Healthcare Systems, LLC; . Dr. Fahn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Retrophin Inc . Dr. Fahn has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Publishers . Dr. Fahn has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Kirkland & Ellis. Dr. Fahn has received publishing royalties from a publication relating to health care.
Cheryl H. Waters, MD, FAAN (Columbia University) Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for US world meds. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexza. Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acorda. Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acadia. Dr. Waters has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurocrine. Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bial. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for US world meds. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lundbeck. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Adamas. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunovion. Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal.
Oury Monchi, PhD (Al) The institution of Dr. Monchi has received research support from Canadian Health Research Institutes. The institution of Dr. Monchi has received research support from National Science and Engineering and Research Council of Canada. The institution of Dr. Monchi has received research support from Brain Canada Parkinson Canada.
Yves Dauvilliers, MD, PhD (Hopital Gui De Chaulliac) Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for idorsia. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for JAZZ. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alkermes. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Centessa. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bioprojet. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Harmony Bioscience.
Nicolas Dupre, MD, FAAN (CHU de Quebec - U Laval) Dr. Dupre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Akcea Therapeutics Canada. The institution of Dr. Dupre has received research support from ARSACS Foundation. The institution of Dr. Dupre has received research support from CHUdeQuebec Foundation.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Sharon Hassin-Baer, MD (Chaim Sheba Medical Center) Dr. Hassin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ABBVIE. Dr. Hassin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MEDISON. Dr. Hassin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TEVA. Dr. Hassin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ABBVIE. Dr. Hassin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ABBVIE. Dr. Hassin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA.
Roy Alcalay, MD (Columbia University) Dr. Alcalay has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme/Sanofi. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gain Therapeutics. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vanqua Bio. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Capsida. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. The institution of Dr. Alcalay has received research support from Michael J. Fox Foundation. The institution of Dr. Alcalay has received research support from Parkinson's Foundation. The institution of Dr. Alcalay has received research support from Silverstein Foundation. Dr. Alcalay has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant with Parkinson's Foundation.
Ziv Gan-Or, MD, PhD (McGill University) Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Gan-Or has received personal compensation in the range of $0-$499 for serving as a Consultant for Lighthouse. Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Therapeutics. Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Handl Therapeutics. Dr. Gan-Or has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial Biotech.