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Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease: Evidence From the COURAGE-PD Consortium.
Grover, Sandeep; Kumar Sreelatha, Ashwin Ashok; Pihlstrom, Lasse; Domenighetti, Cloé; Schulte, Claudia; Sugier, Pierre-Emmanuel; Radivojkov-Blagojevic, Milena; Lichtner, Peter; Mohamed, Océane; Portugal, Berta; Landoulsi, Zied; May, Patrick; Bobbili, Dheeraj; Edsall, Connor; Bartusch, Felix; Hanussek, Maximilian; Krüger, Jens; Hernandez, Dena G; Blauwendraat, Cornelis; Mellick, George D; Zimprich, Alexander; Pirker, Walter; Tan, Manuela; Rogaeva, Ekaterina; Lang, Anthony; Koks, Sulev; Taba, Pille; Lesage, Suzanne; Brice, Alexis; Corvol, Jean-Christophe; Chartier-Harlin, Marie-Christine; Mutez, Eugenie; Brockmann, Kathrin; Deutschländer, Angela B; Hadjigeorgiou, Georges M; Dardiotis, Efthimos; Stefanis, Leonidas; Simitsi, Athina Maria; Valente, Enza Maria; Petrucci, Simona; Straniero, Letizia; Zecchinelli, Anna; Pezzoli, Gianni; Brighina, Laura; Ferrarese, Carlo; Annesi, Grazia; Quattrone, Andrea; Gagliardi, Monica; Burbulla, Lena F; Matsuo, Hirotaka.
Afiliación
  • Grover S; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Kumar Sreelatha AA; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Pihlstrom L; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Domenighetti C; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Schulte C; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Sugier PE; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Radivojkov-Blagojevic M; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Lichtner P; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Mohamed O; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Portugal B; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Landoulsi Z; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • May P; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Bobbili D; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Edsall C; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Bartusch F; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Hanussek M; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Krüger J; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Hernandez DG; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Blauwendraat C; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Mellick GD; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Zimprich A; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Pirker W; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Tan M; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Rogaeva E; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Lang A; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Koks S; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Taba P; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Lesage S; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Brice A; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Corvol JC; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Chartier-Harlin MC; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Mutez E; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Brockmann K; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Deutschländer AB; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Hadjigeorgiou GM; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Dardiotis E; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Stefanis L; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Simitsi AM; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Valente EM; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Petrucci S; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Straniero L; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Zecchinelli A; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Pezzoli G; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Brighina L; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Ferrarese C; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Annesi G; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Quattrone A; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Gagliardi M; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Burbulla LF; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
  • Matsuo H; From the Centre for Genetic Epidemiology (S.G., A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany; Department of Neurology (L. Pihlstrom, M.T.), Oslo University Hospital, Norway; Université Paris-Saclay (C.D., P.E.S., O.M., B.P., A.E.), UVSQ,
Neurology ; 99(7): e698-e710, 2022 08 16.
Article en En | MEDLINE | ID: mdl-35970579
ABSTRACT
BACKGROUND AND

OBJECTIVES:

Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations.

METHODS:

A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC).

RESULTS:

The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9% Europeans and 9.1% East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10-8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025) (rs34311866 ß(SE)COURAGE = 0.477(0.203), p COURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361 ß(SE)COURAGE+IPDGC = 0.720(0.122), p COURAGE+IPDGC = 3.13 × 10-9) and a novel BST1 locus (rs4698412 ß(SE)COURAGE+IPDGC = -0.526(0.096), p COURAGE+IPDGC = 4.41 × 10-8).

DISCUSSION:

Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of BST1 as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Coraje Tipo de estudio: Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans Idioma: En Revista: Neurology Año: 2022 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Coraje Tipo de estudio: Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans Idioma: En Revista: Neurology Año: 2022 Tipo del documento: Article