NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts

Emma N. Somerville; Lynne Krohn; Eric Yu; Uladzislau Rudakou; Konstantin Senkevich; Jennifer A. Ruskey; Farnaz Asayesh; Jamil Ahmad; Dan Spiegelman; Yves Dauvilliers; Isabelle Arnulf; Michele T.M. Hu; Jacques Y. Montplaisir; Jean François Gagnon; Alex Desautels; Abubaker Ibrahim; Ambra Stefani; Birgit Högl; Gian Luigi Gigli; Mariarosaria Valente; Francesco Janes; Andrea Bernardini; Petr Dusek; Karel Sonka; David Kemlink; Giuseppe Plazzi; Elena Antelmi; Francesco Biscarini; Brit Mollenhauer; Claudia Trenkwalder; Friederike Sixel-Doring; Michela Figorilli; Monica Puligheddu; Valerie Cochen De Cock; Wolfgang Oertel; Annette Janzen; Luigi Ferini-Strambi; Anna Heibreder; Christelle Charley Monaca; Beatriz Abril; Femke Dijkstra; Mineke Viaene; Bradley F. Boeve; Ronald B. Postuma; Guy A. Rouleau; Ziv Gan-Or

doi:10.1016/j.neurobiolaging.2023.03.002

NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts

Emma N. Somerville, Lynne Krohn, Eric Yu, Uladzislau Rudakou, Konstantin Senkevich, Jennifer A. Ruskey, Farnaz Asayesh, Jamil Ahmad, Dan Spiegelman, Yves Dauvilliers, Isabelle Arnulf, Michele T.M. Hu, Jacques Y. Montplaisir, Jean François Gagnon, Alex Desautels, Abubaker Ibrahim, Ambra Stefani, Birgit Högl, Gian Luigi Gigli, Mariarosaria ValenteFrancesco Janes, Andrea Bernardini, Petr Dusek, Karel Sonka, David Kemlink, Giuseppe Plazzi, Elena Antelmi, Francesco Biscarini, Brit Mollenhauer, Claudia Trenkwalder, Friederike Sixel-Doring, Michela Figorilli, Monica Puligheddu, Valerie Cochen De Cock, Wolfgang Oertel, Annette Janzen, Luigi Ferini-Strambi, Anna Heibreder, Christelle Charley Monaca, Beatriz Abril, Femke Dijkstra, Mineke Viaene, Bradley F. Boeve, Ronald B. Postuma, Guy A. Rouleau, Ziv Gan-Or

Neurology

Research output: Contribution to journal › Article › peer-review

Abstract

NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to evaluate the association of NPC1 variants with the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and rapid eye movement–sleep behavior disorder (RBD). We analyzed common and rare variants from 3 cohorts of European descent: 1084 RBD cases and 2945 controls, 2852 PD cases and 1686 controls, and 2610 DLB cases and 1920 controls. Logistic regression models were used to assess common variants while optimal sequence Kernel association tests were used to assess rare variants, both adjusted for sex, age, and principal components. No variants were associated with any of the synucleinopathies, supporting that common and rare NPC1 variants do not play an important role in alpha synucleinopathies.

Original language	English (US)
Pages (from-to)	94-98
Number of pages	5
Journal	Neurobiology of aging
Volume	127
DOIs	https://doi.org/10.1016/j.neurobiolaging.2023.03.002
State	Published - Jul 2023

Keywords

Association study
Dementia with Lewy bodies
NPC1
Niemann-Pick disease type C
Parkinson's disease
REM-sleep behavior disorder

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2023.03.002

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Somerville, E. N., Krohn, L., Yu, E., Rudakou, U., Senkevich, K., Ruskey, J. A., Asayesh, F., Ahmad, J., Spiegelman, D., Dauvilliers, Y., Arnulf, I., Hu, M. T. M., Montplaisir, J. Y., Gagnon, J. F., Desautels, A., Ibrahim, A., Stefani, A., Högl, B., Gigli, G. L., ... Gan-Or, Z. (2023). NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts. Neurobiology of aging, 127, 94-98. https://doi.org/10.1016/j.neurobiolaging.2023.03.002

Somerville, EN, Krohn, L, Yu, E, Rudakou, U, Senkevich, K, Ruskey, JA, Asayesh, F, Ahmad, J, Spiegelman, D, Dauvilliers, Y, Arnulf, I, Hu, MTM, Montplaisir, JY, Gagnon, JF, Desautels, A, Ibrahim, A, Stefani, A, Högl, B, Gigli, GL, Valente, M, Janes, F, Bernardini, A, Dusek, P, Sonka, K, Kemlink, D, Plazzi, G, Antelmi, E, Biscarini, F, Mollenhauer, B, Trenkwalder, C, Sixel-Doring, F, Figorilli, M, Puligheddu, M, De Cock, VC, Oertel, W, Janzen, A, Ferini-Strambi, L, Heibreder, A, Monaca, CC, Abril, B, Dijkstra, F, Viaene, M, Boeve, BF, Postuma, RB, Rouleau, GA & Gan-Or, Z 2023, 'NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts', Neurobiology of aging, vol. 127, pp. 94-98. https://doi.org/10.1016/j.neurobiolaging.2023.03.002

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title = "NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts",

abstract = "NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to evaluate the association of NPC1 variants with the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and rapid eye movement–sleep behavior disorder (RBD). We analyzed common and rare variants from 3 cohorts of European descent: 1084 RBD cases and 2945 controls, 2852 PD cases and 1686 controls, and 2610 DLB cases and 1920 controls. Logistic regression models were used to assess common variants while optimal sequence Kernel association tests were used to assess rare variants, both adjusted for sex, age, and principal components. No variants were associated with any of the synucleinopathies, supporting that common and rare NPC1 variants do not play an important role in alpha synucleinopathies.",

keywords = "Association study, Dementia with Lewy bodies, NPC1, Niemann-Pick disease type C, Parkinson's disease, REM-sleep behavior disorder",

author = "Somerville, {Emma N.} and Lynne Krohn and Eric Yu and Uladzislau Rudakou and Konstantin Senkevich and Ruskey, {Jennifer A.} and Farnaz Asayesh and Jamil Ahmad and Dan Spiegelman and Yves Dauvilliers and Isabelle Arnulf and Hu, {Michele T.M.} and Montplaisir, {Jacques Y.} and Gagnon, {Jean Fran{\c c}ois} and Alex Desautels and Abubaker Ibrahim and Ambra Stefani and Birgit H{\"o}gl and Gigli, {Gian Luigi} and Mariarosaria Valente and Francesco Janes and Andrea Bernardini and Petr Dusek and Karel Sonka and David Kemlink and Giuseppe Plazzi and Elena Antelmi and Francesco Biscarini and Brit Mollenhauer and Claudia Trenkwalder and Friederike Sixel-Doring and Michela Figorilli and Monica Puligheddu and {De Cock}, {Valerie Cochen} and Wolfgang Oertel and Annette Janzen and Luigi Ferini-Strambi and Anna Heibreder and Monaca, {Christelle Charley} and Beatriz Abril and Femke Dijkstra and Mineke Viaene and Boeve, {Bradley F.} and Postuma, {Ronald B.} and Rouleau, {Guy A.} and Ziv Gan-Or",

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doi = "10.1016/j.neurobiolaging.2023.03.002",

language = "English (US)",

volume = "127",

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T1 - NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts

AU - Somerville, Emma N.

AU - Krohn, Lynne

AU - Yu, Eric

AU - Rudakou, Uladzislau

AU - Senkevich, Konstantin

AU - Ruskey, Jennifer A.

AU - Asayesh, Farnaz

AU - Ahmad, Jamil

AU - Spiegelman, Dan

AU - Dauvilliers, Yves

AU - Arnulf, Isabelle

AU - Hu, Michele T.M.

AU - Montplaisir, Jacques Y.

AU - Gagnon, Jean François

AU - Desautels, Alex

AU - Ibrahim, Abubaker

AU - Stefani, Ambra

AU - Högl, Birgit

AU - Gigli, Gian Luigi

AU - Valente, Mariarosaria

AU - Janes, Francesco

AU - Bernardini, Andrea

AU - Dusek, Petr

AU - Sonka, Karel

AU - Kemlink, David

AU - Plazzi, Giuseppe

AU - Antelmi, Elena

AU - Biscarini, Francesco

AU - Mollenhauer, Brit

AU - Trenkwalder, Claudia

AU - Sixel-Doring, Friederike

AU - Figorilli, Michela

AU - Puligheddu, Monica

AU - De Cock, Valerie Cochen

AU - Oertel, Wolfgang

AU - Janzen, Annette

AU - Ferini-Strambi, Luigi

AU - Heibreder, Anna

AU - Monaca, Christelle Charley

AU - Abril, Beatriz

AU - Dijkstra, Femke

AU - Viaene, Mineke

AU - Boeve, Bradley F.

AU - Postuma, Ronald B.

AU - Rouleau, Guy A.

AU - Gan-Or, Ziv

PY - 2023/7

Y1 - 2023/7

N2 - NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to evaluate the association of NPC1 variants with the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and rapid eye movement–sleep behavior disorder (RBD). We analyzed common and rare variants from 3 cohorts of European descent: 1084 RBD cases and 2945 controls, 2852 PD cases and 1686 controls, and 2610 DLB cases and 1920 controls. Logistic regression models were used to assess common variants while optimal sequence Kernel association tests were used to assess rare variants, both adjusted for sex, age, and principal components. No variants were associated with any of the synucleinopathies, supporting that common and rare NPC1 variants do not play an important role in alpha synucleinopathies.

AB - NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to evaluate the association of NPC1 variants with the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and rapid eye movement–sleep behavior disorder (RBD). We analyzed common and rare variants from 3 cohorts of European descent: 1084 RBD cases and 2945 controls, 2852 PD cases and 1686 controls, and 2610 DLB cases and 1920 controls. Logistic regression models were used to assess common variants while optimal sequence Kernel association tests were used to assess rare variants, both adjusted for sex, age, and principal components. No variants were associated with any of the synucleinopathies, supporting that common and rare NPC1 variants do not play an important role in alpha synucleinopathies.

KW - Association study

KW - Dementia with Lewy bodies

KW - NPC1

KW - Niemann-Pick disease type C

KW - Parkinson's disease

KW - REM-sleep behavior disorder

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U2 - 10.1016/j.neurobiolaging.2023.03.002

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AN - SCOPUS:85152436013

SN - 0197-4580

VL - 127

SP - 94

EP - 98

JO - Neurobiology of aging

JF - Neurobiology of aging

ER -

NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts

Abstract

Keywords

ASJC Scopus subject areas

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