Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Michael A. Van Es; Helenius J. Schelhaas; Paul W.J. Van Vught; Nicola Ticozzi; Peter M. Andersen; Ewout J.N. Groen; Claudia Schulte; Hylke M. Blauw; Max Koppers; Frank P. Diekstra; Katsumi Fumoto; Ashley Lyn Leclerc; Pamela Keagle; Bastiaan R. Bloem; Hans Scheffer; Bart F.L. Van Nuenen; Marka Van Blitterswijk; Wouter Van Rheenen; Anne Marie Wills; Patrick P. Lowe; Guo Fu Hu; Wenhao Yu; Hiroko Kishikawa; David Wu; Rebecca D. Folkerth; Claudio Mariani; Stefano Goldwurm; Gianni Pezzoli; Philip Van Damme; Robin Lemmens; Caroline Dahlberg; Anna Birve; Rubén Fernández-Santiago; Stefan Waibel; Christine Klein; Markus Weber; Anneke J. Van Der Kooi; Marianne De Visser; Dagmar Verbaan; Jacobus J. Van Hilten; Peter Heutink; Eric A.M. Hennekam; Edwin Cuppen; Daniela Berg; Robert H. Brown; Vincenzo Silani; Thomas Gasser; Albert C. Ludolph; Wim Robberecht; Roel A. Ophoff; Jan H. Veldink; R. Jeroen Pasterkamp; Paul I.W. De Bakker; John E. Landers; Bart P. Van De Warrenburg; Leonard H. Van Den Berg

doi:10.1002/ana.22611

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Michael A. Van Es, Helenius J. Schelhaas, Paul W.J. Van Vught, Nicola Ticozzi, Peter M. Andersen, Ewout J.N. Groen, Claudia Schulte, Hylke M. Blauw, Max Koppers, Frank P. Diekstra, Katsumi Fumoto, Ashley Lyn Leclerc, Pamela Keagle, Bastiaan R. Bloem, Hans Scheffer, Bart F.L. Van Nuenen, Marka Van Blitterswijk, Wouter Van Rheenen, Anne Marie Wills, Patrick P. LoweGuo Fu Hu, Wenhao Yu, Hiroko Kishikawa, David Wu, Rebecca D. Folkerth, Claudio Mariani, Stefano Goldwurm, Gianni Pezzoli, Philip Van Damme, Robin Lemmens, Caroline Dahlberg, Anna Birve, Rubén Fernández-Santiago, Stefan Waibel, Christine Klein, Markus Weber, Anneke J. Van Der Kooi, Marianne De Visser, Dagmar Verbaan, Jacobus J. Van Hilten, Peter Heutink, Eric A.M. Hennekam, Edwin Cuppen, Daniela Berg, Robert H. Brown, Vincenzo Silani, Thomas Gasser, Albert C. Ludolph, Wim Robberecht, Roel A. Ophoff, Jan H. Veldink, R. Jeroen Pasterkamp, Paul I.W. De Bakker, John E. Landers, Bart P. Van De Warrenburg, Leonard H. Van Den Berg

Neuroscience

Research output: Contribution to journal › Review article › peer-review

138 Scopus citations

Abstract

Objective: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. Results: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10 ^-6 for ALS and p = 4.3 × 10 ^-5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.

Original language	English (US)
Pages (from-to)	964-973
Number of pages	10
Journal	Annals of neurology
Volume	70
Issue number	6
DOIs	https://doi.org/10.1002/ana.22611
State	Published - Dec 2011

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/ana.22611

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Van Es, M. A., Schelhaas, H. J., Van Vught, P. W. J., Ticozzi, N., Andersen, P. M., Groen, E. J. N., Schulte, C., Blauw, H. M., Koppers, M., Diekstra, F. P., Fumoto, K., Leclerc, A. L., Keagle, P., Bloem, B. R., Scheffer, H., Van Nuenen, B. F. L., Van Blitterswijk, M., Van Rheenen, W., Wills, A. M., ... Van Den Berg, L. H. (2011). Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. Annals of neurology, 70(6), 964-973. https://doi.org/10.1002/ana.22611

Van Es, MA, Schelhaas, HJ, Van Vught, PWJ, Ticozzi, N, Andersen, PM, Groen, EJN, Schulte, C, Blauw, HM, Koppers, M, Diekstra, FP, Fumoto, K, Leclerc, AL, Keagle, P, Bloem, BR, Scheffer, H, Van Nuenen, BFL, Van Blitterswijk, M, Van Rheenen, W, Wills, AM, Lowe, PP, Hu, GF, Yu, W, Kishikawa, H, Wu, D, Folkerth, RD, Mariani, C, Goldwurm, S, Pezzoli, G, Van Damme, P, Lemmens, R, Dahlberg, C, Birve, A, Fernández-Santiago, R, Waibel, S, Klein, C, Weber, M, Van Der Kooi, AJ, De Visser, M, Verbaan, D, Van Hilten, JJ, Heutink, P, Hennekam, EAM, Cuppen, E, Berg, D, Brown, RH, Silani, V, Gasser, T, Ludolph, AC, Robberecht, W, Ophoff, RA, Veldink, JH, Pasterkamp, RJ, De Bakker, PIW, Landers, JE, Van De Warrenburg, BP & Van Den Berg, LH 2011, 'Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis', Annals of neurology, vol. 70, no. 6, pp. 964-973. https://doi.org/10.1002/ana.22611

@article{d78d0cb9163d48c786a299ae66b16cd5,

title = "Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis",

abstract = "Objective: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. Results: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10 -6 for ALS and p = 4.3 × 10 -5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.",

author = "{Van Es}, {Michael A.} and Schelhaas, {Helenius J.} and {Van Vught}, {Paul W.J.} and Nicola Ticozzi and Andersen, {Peter M.} and Groen, {Ewout J.N.} and Claudia Schulte and Blauw, {Hylke M.} and Max Koppers and Diekstra, {Frank P.} and Katsumi Fumoto and Leclerc, {Ashley Lyn} and Pamela Keagle and Bloem, {Bastiaan R.} and Hans Scheffer and {Van Nuenen}, {Bart F.L.} and {Van Blitterswijk}, Marka and {Van Rheenen}, Wouter and Wills, {Anne Marie} and Lowe, {Patrick P.} and Hu, {Guo Fu} and Wenhao Yu and Hiroko Kishikawa and David Wu and Folkerth, {Rebecca D.} and Claudio Mariani and Stefano Goldwurm and Gianni Pezzoli and {Van Damme}, Philip and Robin Lemmens and Caroline Dahlberg and Anna Birve and Rub{\'e}n Fern{\'a}ndez-Santiago and Stefan Waibel and Christine Klein and Markus Weber and {Van Der Kooi}, {Anneke J.} and {De Visser}, Marianne and Dagmar Verbaan and {Van Hilten}, {Jacobus J.} and Peter Heutink and Hennekam, {Eric A.M.} and Edwin Cuppen and Daniela Berg and Brown, {Robert H.} and Vincenzo Silani and Thomas Gasser and Ludolph, {Albert C.} and Wim Robberecht and Ophoff, {Roel A.} and Veldink, {Jan H.} and Pasterkamp, {R. Jeroen} and {De Bakker}, {Paul I.W.} and Landers, {John E.} and {Van De Warrenburg}, {Bart P.} and {Van Den Berg}, {Leonard H.}",

year = "2011",

month = dec,

doi = "10.1002/ana.22611",

language = "English (US)",

volume = "70",

pages = "964--973",

journal = "Annals of neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "6",

}

TY - JOUR

T1 - Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

AU - Van Es, Michael A.

AU - Schelhaas, Helenius J.

AU - Van Vught, Paul W.J.

AU - Ticozzi, Nicola

AU - Andersen, Peter M.

AU - Groen, Ewout J.N.

AU - Schulte, Claudia

AU - Blauw, Hylke M.

AU - Koppers, Max

AU - Diekstra, Frank P.

AU - Fumoto, Katsumi

AU - Leclerc, Ashley Lyn

AU - Keagle, Pamela

AU - Bloem, Bastiaan R.

AU - Scheffer, Hans

AU - Van Nuenen, Bart F.L.

AU - Van Blitterswijk, Marka

AU - Van Rheenen, Wouter

AU - Wills, Anne Marie

AU - Lowe, Patrick P.

AU - Hu, Guo Fu

AU - Yu, Wenhao

AU - Kishikawa, Hiroko

AU - Wu, David

AU - Folkerth, Rebecca D.

AU - Mariani, Claudio

AU - Goldwurm, Stefano

AU - Pezzoli, Gianni

AU - Van Damme, Philip

AU - Lemmens, Robin

AU - Dahlberg, Caroline

AU - Birve, Anna

AU - Fernández-Santiago, Rubén

AU - Waibel, Stefan

AU - Klein, Christine

AU - Weber, Markus

AU - Van Der Kooi, Anneke J.

AU - De Visser, Marianne

AU - Verbaan, Dagmar

AU - Van Hilten, Jacobus J.

AU - Heutink, Peter

AU - Hennekam, Eric A.M.

AU - Cuppen, Edwin

AU - Berg, Daniela

AU - Brown, Robert H.

AU - Silani, Vincenzo

AU - Gasser, Thomas

AU - Ludolph, Albert C.

AU - Robberecht, Wim

AU - Ophoff, Roel A.

AU - Veldink, Jan H.

AU - Pasterkamp, R. Jeroen

AU - De Bakker, Paul I.W.

AU - Landers, John E.

AU - Van De Warrenburg, Bart P.

AU - Van Den Berg, Leonard H.

PY - 2011/12

Y1 - 2011/12

N2 - Objective: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. Results: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10 -6 for ALS and p = 4.3 × 10 -5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.

AB - Objective: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. Results: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10 -6 for ALS and p = 4.3 × 10 -5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.

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U2 - 10.1002/ana.22611

DO - 10.1002/ana.22611

M3 - Review article

C2 - 22190368

AN - SCOPUS:84255163614

SN - 0364-5134

VL - 70

SP - 964

EP - 973

JO - Annals of neurology

JF - Annals of neurology

IS - 6

ER -

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

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