GBA and APOE epsilon 4 associate with sporadic dementia with Lewy bodies in European genome wide association study
Por:
Rongve, A, Witoelar, A, Ruiz, A, Athanasiu, L, Abdelnour, C, Clarimon, J, Heilmann-Heimbach, S, Hernandez, I, Moreno-Grau, S, de Rojas, I, Morenas-Rodriguez, E, Fladby, T, Sando, SB, Brathen, G, Blanc, F, Bousiges, O, Lemstra, AW, van Steenoven, I, Londos, E, Almdahl, IS, Palhaugen, L, Eriksen, JA, Djurovic, S, Stordal, E, Saltvedt, I, Ulstein, ID, Bettella, F, Desikan, RS, Idland, AV, Toft, M, Pihlstrom, L, Snaedal, J, Tarraga, L, Boada, M, Lleo, A, Stefansson, H, Stefansson, K, Ramirez, A, Aarsland, D, Andreassen, OA
Publicada:
7 may 2019
Resumen:
Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE epsilon 4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 x 10(-8)). One additional genetic locus previously linked to psychosis in Alzheimer's disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 x 10(-6). We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.
Filiaciones:
Rongve, A:
Haugesund Hosp, Dept Res & Innovat, Helse Fonna, Haugesund, Norway
Univ Bergen, Dept Clin Med K1, Bergen, Norway
Witoelar, A:
Oslo Univ Hosp, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, NORMENT, Oslo, Norway
Univ Oslo, Inst Clin Med, Oslo, Norway
Ruiz, A:
UIC, Inst Catala Neurociencies Aplicades, MemoryClin & Res Ctr Fundacio ACE, Barcelona, Spain
Athanasiu, L:
Oslo Univ Hosp, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, NORMENT, Oslo, Norway
Univ Oslo, Inst Clin Med, Oslo, Norway
Abdelnour, C:
UIC, Inst Catala Neurociencies Aplicades, MemoryClin & Res Ctr Fundacio ACE, Barcelona, Spain
Clarimon, J:
Univ Autenoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, IIB St Pau, Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Heilmann-Heimbach, S:
Univ Bonn, Inst Human Genet, Bonn, Germany
Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany
Hernandez, I:
UIC, Inst Catala Neurociencies Aplicades, MemoryClin & Res Ctr Fundacio ACE, Barcelona, Spain
Moreno-Grau, S:
UIC, Inst Catala Neurociencies Aplicades, MemoryClin & Res Ctr Fundacio ACE, Barcelona, Spain
de Rojas, I:
UIC, Inst Catala Neurociencies Aplicades, MemoryClin & Res Ctr Fundacio ACE, Barcelona, Spain
Morenas-Rodriguez, E:
Univ Autenoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, IIB St Pau, Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Fladby, T:
Akershus Univ Hosp, Dept Neurol, Lorenskog, Norway
Univ Oslo, AHUS Campus, Oslo, Norway
Sando, SB:
Norwegian Univ Sci & Technol, Dept Neuromed & Movement Sci, Trondheim, Norway
Brathen, G:
St Olavs Hosp, Dept Neurol, Trondheim, Norway
Blanc, F:
Univ Hosp Strasbourg, CMRR Memory Resources & Res Ctr, Geriatr Dept, Strasbourg, France
Univ Strasbourg, ICube Lab & FMTS, Team IMIS Neurocrypto, Strasbourg, France
CNRS, ICube Lab & FMTS, Team IMIS Neurocrypto, Strasbourg, France
Bousiges, O:
Univ Hosp Strasbourg, CMRR Memory Resources & Res Ctr, Lab Biochem & Mol Biol, Strasbourg, France
Lemstra, AW:
Univ Strasbourg & CNRS, Lab Neurosci Cognit & Adaptat LNCA, UMR7364, F-67000 Strasbourg, France
Vrije Univ Amsterdam Med Ctr, Alzheimerctr, Amsterdam, Netherlands
Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands
van Steenoven, I:
Univ Strasbourg & CNRS, Lab Neurosci Cognit & Adaptat LNCA, UMR7364, F-67000 Strasbourg, France
Vrije Univ Amsterdam Med Ctr, Alzheimerctr, Amsterdam, Netherlands
Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands
Londos, E:
Lund Univ, Skane Univ Hosp, Inst Clin Sci, Malmo, Sweden
Almdahl, IS:
Univ Oslo, AHUS Campus, Oslo, Norway
Oslo Univ Hosp, Dept Geriatr Psychiat, Oslo, Norway
Palhaugen, L:
Akershus Univ Hosp, Dept Neurol, Lorenskog, Norway
Univ Oslo, AHUS Campus, Oslo, Norway
Eriksen, JA:
Oslo Univ Hosp, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, NORMENT, Oslo, Norway
Univ Oslo, Inst Clin Med, Oslo, Norway
Djurovic, S:
Oslo Univ Hosp, Dept Med Genet, Oslo, Norway
Univ Bergen, KG Jebsen Ctr Psychosis Res, Dept Clin Sci, NORMENT, Bergen, Norway
Stordal, E:
Namsos Hosp, Dept Psychiat, Namsos, Norway
Norwegian Univ Sci & Technol, Dept Mental Hlth, Trondheim, Norway
Saltvedt, I:
Norwegian Univ Sci & Technol, Dept Neuromed & Movement Sci, Trondheim, Norway
St Olavs Hosp, Dept Geriatr, Trondheim, Norway
Ulstein, ID:
Univ Oslo, Inst Clin Med, Oslo, Norway
Oslo Univ Hosp, Dept Geriatr Psychiat, Oslo, Norway
Bettella, F:
Oslo Univ Hosp, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, NORMENT, Oslo, Norway
Desikan, RS:
UCSF, Dept Radiol & Biomed Imaging Neurol & Pediat, San Francisco, CA USA
Idland, AV:
Univ Oslo, Inst Clin Med, Dept Geriatr Med, Oslo Delirium Res Grp, Oslo, Norway
Univ Oslo, Dept Psychol, Res Grp Lifespan Changes Brain & Cognit, Oslo, Norway
Univ Oslo, Inst Basic Med Sci, Oslo, Norway
Toft, M:
Univ Oslo, Inst Clin Med, Oslo, Norway
Oslo Univ Hosp, Dept Neurol, Oslo, Norway
Pihlstrom, L:
Oslo Univ Hosp, Dept Neurol, Oslo, Norway
Snaedal, J:
Landspitali Univ Hosp, Reykjavik, Iceland
Tarraga, L:
UIC, Inst Catala Neurociencies Aplicades, MemoryClin & Res Ctr Fundacio ACE, Barcelona, Spain
Boada, M:
UIC, Inst Catala Neurociencies Aplicades, MemoryClin & Res Ctr Fundacio ACE, Barcelona, Spain
Lleo, A:
Univ Autenoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, IIB St Pau, Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Stefansson, H:
DeCODE Genet, Reykjavik, Iceland
Stefansson, K:
DeCODE Genet, Reykjavik, Iceland
Ramirez, A:
Univ Cologne, Med Fac, Dept Psychiat & Psychotherapy, Div Neurogenet & Mol Psychiat, D-50924 Cologne, Germany
Univ Bonn, Dept Neurodegenerat Dis & Geriatr Psychiat, D-53127 Bonn, Germany
Aarsland, D:
Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England
Stavanger Univ Hosp, Ctr Age Related Dis, Stavanger, Norway
Andreassen, OA:
Oslo Univ Hosp, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, NORMENT, Oslo, Norway
Univ Oslo, Inst Clin Med, Oslo, Norway
Gold, Green Published
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