Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population

Anamika Giri, Kin Y. Mok, Iris Jansen, Manu Sharma, Christelle Tesson, Graziella Mangone, Suzanne Lesage, José M. Bras, Joshua M. Shulman, Una Marie Sheerin, Mónica Díez-Fairen, Pau Pastor, María José Martí, Mario Ezquerra, Eduardo Tolosa, Leonor Correia-Guedes, Joaquim Ferreira, Najaf Amin, Cornelia M. van Duijn, Jeroen van Rooij & 5 others André G. Uitterlinden, Robert Kraaij, Michael Nalls, Javier Simón-Sánchez, International Parkinson's Disease Consortium (IPDGC)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.

Original languageEnglish
Pages (from-to)167.e11-167.e13
JournalNeurobiology of Aging
Volume50
DOIs
Publication statusPublished - 1 Feb 2017

Cite this

Giri, A., Mok, K. Y., Jansen, I., Sharma, M., Tesson, C., Mangone, G., ... International Parkinson's Disease Consortium (IPDGC) (2017). Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population. Neurobiology of Aging, 50, 167.e11-167.e13. https://doi.org/10.1016/j.neurobiolaging.2016.10.004
Giri, Anamika ; Mok, Kin Y. ; Jansen, Iris ; Sharma, Manu ; Tesson, Christelle ; Mangone, Graziella ; Lesage, Suzanne ; Bras, José M. ; Shulman, Joshua M. ; Sheerin, Una Marie ; Díez-Fairen, Mónica ; Pastor, Pau ; Martí, María José ; Ezquerra, Mario ; Tolosa, Eduardo ; Correia-Guedes, Leonor ; Ferreira, Joaquim ; Amin, Najaf ; van Duijn, Cornelia M. ; van Rooij, Jeroen ; Uitterlinden, André G. ; Kraaij, Robert ; Nalls, Michael ; Simón-Sánchez, Javier ; International Parkinson's Disease Consortium (IPDGC). / Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population. In: Neurobiology of Aging. 2017 ; Vol. 50. pp. 167.e11-167.e13.
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title = "Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population",
abstract = "Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.",
keywords = "IPDGC, Mutation screening, Parkinson's disease, Rotterdam Study Exome Sequencing Database, SKAT-O, TMEM230",
author = "Anamika Giri and Mok, {Kin Y.} and Iris Jansen and Manu Sharma and Christelle Tesson and Graziella Mangone and Suzanne Lesage and Bras, {Jos{\'e} M.} and Shulman, {Joshua M.} and Sheerin, {Una Marie} and M{\'o}nica D{\'i}ez-Fairen and Pau Pastor and Mart{\'i}, {Mar{\'i}a Jos{\'e}} and Mario Ezquerra and Eduardo Tolosa and Leonor Correia-Guedes and Joaquim Ferreira and Najaf Amin and {van Duijn}, {Cornelia M.} and {van Rooij}, Jeroen and Uitterlinden, {Andr{\'e} G.} and Robert Kraaij and Michael Nalls and Javier Sim{\'o}n-S{\'a}nchez and {International Parkinson's Disease Consortium (IPDGC)}",
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Giri, A, Mok, KY, Jansen, I, Sharma, M, Tesson, C, Mangone, G, Lesage, S, Bras, JM, Shulman, JM, Sheerin, UM, Díez-Fairen, M, Pastor, P, Martí, MJ, Ezquerra, M, Tolosa, E, Correia-Guedes, L, Ferreira, J, Amin, N, van Duijn, CM, van Rooij, J, Uitterlinden, AG, Kraaij, R, Nalls, M, Simón-Sánchez, J & International Parkinson's Disease Consortium (IPDGC) 2017, 'Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population' Neurobiology of Aging, vol. 50, pp. 167.e11-167.e13. https://doi.org/10.1016/j.neurobiolaging.2016.10.004

Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population. / Giri, Anamika; Mok, Kin Y.; Jansen, Iris; Sharma, Manu; Tesson, Christelle; Mangone, Graziella; Lesage, Suzanne; Bras, José M.; Shulman, Joshua M.; Sheerin, Una Marie; Díez-Fairen, Mónica; Pastor, Pau; Martí, María José; Ezquerra, Mario; Tolosa, Eduardo; Correia-Guedes, Leonor; Ferreira, Joaquim; Amin, Najaf; van Duijn, Cornelia M.; van Rooij, Jeroen; Uitterlinden, André G.; Kraaij, Robert; Nalls, Michael; Simón-Sánchez, Javier; International Parkinson's Disease Consortium (IPDGC).

In: Neurobiology of Aging, Vol. 50, 01.02.2017, p. 167.e11-167.e13.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population

AU - Giri, Anamika

AU - Mok, Kin Y.

AU - Jansen, Iris

AU - Sharma, Manu

AU - Tesson, Christelle

AU - Mangone, Graziella

AU - Lesage, Suzanne

AU - Bras, José M.

AU - Shulman, Joshua M.

AU - Sheerin, Una Marie

AU - Díez-Fairen, Mónica

AU - Pastor, Pau

AU - Martí, María José

AU - Ezquerra, Mario

AU - Tolosa, Eduardo

AU - Correia-Guedes, Leonor

AU - Ferreira, Joaquim

AU - Amin, Najaf

AU - van Duijn, Cornelia M.

AU - van Rooij, Jeroen

AU - Uitterlinden, André G.

AU - Kraaij, Robert

AU - Nalls, Michael

AU - Simón-Sánchez, Javier

AU - International Parkinson's Disease Consortium (IPDGC)

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.

AB - Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.

KW - IPDGC

KW - Mutation screening

KW - Parkinson's disease

KW - Rotterdam Study Exome Sequencing Database

KW - SKAT-O

KW - TMEM230

UR - http://www.scopus.com/inward/record.url?scp=85006102600&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2016.10.004

DO - 10.1016/j.neurobiolaging.2016.10.004

M3 - Article

VL - 50

SP - 167.e11-167.e13

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -