ATXN2 trinucleotide repeat length correlates with risk of ALS

William Sproviero; Aleksey Shatunov; Daniel Stahl; Maryam Shoai; Wouter Van Rheenen; Ashley R. Jones; Safa Al-Sarraj; Peter M. Andersen; Nancy M. Bonini; Francesca L. Conforti; Philip Van Damme; Hussein Daoud; Maria Del Mar Amador; Isabella Fogh; Monica Forzan; Ben Gaastra; Cinzia Gellera; Aaron D. Gitler; John Hardy; Pietro Fratta; Vincenzo La Bella; Isabelle Le Ber; Tim Van Langenhove; Serena Lattante; Yi-Chung Lee; Andrea Malaspina; Vincent Meininger; Stéphanie Millecamps; Richard Orrell; Rosa Rademakers; Wim Robberecht; Guy Rouleau; Owen A. Ross; Francois Salachas; Katie Sidle; Bradley N. Smith; Bing-Wen Soong; Gianni Sorarù; Giovanni Stevanin; Edor Kabashi; Claire Troakes; Christine Van Broeckhoven; Jan H. Veldink; Leonard H. Van Den Berg; Christopher E. Shaw; John F. Powell; Ammar Al-Chalabi

doi:10.1016/j.neurobiolaging.2016.11.010

ATXN2 trinucleotide repeat length correlates with risk of ALS

William Sproviero, Aleksey Shatunov, Daniel Stahl, Maryam Shoai, Wouter Van Rheenen, Ashley R. Jones, Safa Al-Sarraj, Peter M. Andersen, Nancy M. Bonini, Francesca L. Conforti, Philip Van Damme, Hussein Daoud, Maria Del Mar Amador, Isabella Fogh, Monica Forzan, Ben Gaastra, Cinzia Gellera, Aaron D. Gitler, John Hardy, Pietro FrattaVincenzo La Bella, Isabelle Le Ber, Tim Van Langenhove, Serena Lattante, Yi-Chung Lee, Andrea Malaspina, Vincent Meininger, Stéphanie Millecamps, Richard Orrell, Rosa Rademakers, Wim Robberecht, Guy Rouleau, Owen A. Ross, Francois Salachas, Katie Sidle, Bradley N. Smith, Bing-Wen Soong, Gianni Sorarù, Giovanni Stevanin, Edor Kabashi, Claire Troakes, Christine Van Broeckhoven, Jan H. Veldink, Leonard H. Van Den Berg, Christopher E. Shaw, John F. Powell, Ammar Al-Chalabi

Università Cattolica del Sacro Cuore

Risultato della ricerca: Contributo in rivista › Articolo

45 Citazioni (Scopus)

Abstract

We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10-18), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R2 = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.

Lingua originale	Inglese
pagine (da-a)	N/A-N/A
Rivista	Neurobiology of Aging
Volume	51
DOI	https://doi.org/10.1016/j.neurobiolaging.2016.11.010
Stato di pubblicazione	Pubblicato - 2017

Keywords

ALS
ATXN2
Age of onset
Amyotrophic lateral sclerosis
CAG
Expansion
Exponential risk
Intermediate expansion
Risk
SCA2
Trinucleotide repeat
Triplet

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10.1016/j.neurobiolaging.2016.11.010

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Sproviero, W., Shatunov, A., Stahl, D., Shoai, M., Van Rheenen, W., Jones, A. R., Al-Sarraj, S., Andersen, P. M., Bonini, N. M., Conforti, F. L., Van Damme, P., Daoud, H., Del Mar Amador, M., Fogh, I., Forzan, M., Gaastra, B., Gellera, C., Gitler, A. D., Hardy, J., ... Al-Chalabi, A. (2017). ATXN2 trinucleotide repeat length correlates with risk of ALS. Neurobiology of Aging, 51, N/A-N/A. https://doi.org/10.1016/j.neurobiolaging.2016.11.010

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title = "ATXN2 trinucleotide repeat length correlates with risk of ALS",

abstract = "We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95\% confidence interval 2.37-3.94]; p = 6 × 10-18), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R2 = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.",

keywords = "ALS, ATXN2, Age of onset, Amyotrophic lateral sclerosis, CAG, Expansion, Exponential risk, Intermediate expansion, Risk, SCA2, Trinucleotide repeat, Triplet, ALS, ATXN2, Age of onset, Amyotrophic lateral sclerosis, CAG, Expansion, Exponential risk, Intermediate expansion, Risk, SCA2, Trinucleotide repeat, Triplet",

author = "William Sproviero and Aleksey Shatunov and Daniel Stahl and Maryam Shoai and \{Van Rheenen\}, Wouter and Jones, \{Ashley R.\} and Safa Al-Sarraj and Andersen, \{Peter M.\} and Bonini, \{Nancy M.\} and Conforti, \{Francesca L.\} and \{Van Damme\}, Philip and Hussein Daoud and \{Del Mar Amador\}, Maria and Isabella Fogh and Monica Forzan and Ben Gaastra and Cinzia Gellera and Gitler, \{Aaron D.\} and John Hardy and Pietro Fratta and \{La Bella\}, Vincenzo and \{Le Ber\}, Isabelle and \{Van Langenhove\}, Tim and Serena Lattante and Yi-Chung Lee and Andrea Malaspina and Vincent Meininger and St{\'e}phanie Millecamps and Richard Orrell and Rosa Rademakers and Wim Robberecht and Guy Rouleau and Ross, \{Owen A.\} and Francois Salachas and Katie Sidle and Smith, \{Bradley N.\} and Bing-Wen Soong and Gianni Sorar{\`u} and Giovanni Stevanin and Edor Kabashi and Claire Troakes and \{Van Broeckhoven\}, Christine and Veldink, \{Jan H.\} and \{Van Den Berg\}, \{Leonard H.\} and Shaw, \{Christopher E.\} and Powell, \{John F.\} and Ammar Al-Chalabi",

year = "2017",

doi = "10.1016/j.neurobiolaging.2016.11.010",

language = "English",

volume = "51",

pages = "N/A--N/A",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

}

Sproviero, W, Shatunov, A, Stahl, D, Shoai, M, Van Rheenen, W, Jones, AR, Al-Sarraj, S, Andersen, PM, Bonini, NM, Conforti, FL, Van Damme, P, Daoud, H, Del Mar Amador, M, Fogh, I, Forzan, M, Gaastra, B, Gellera, C, Gitler, AD, Hardy, J, Fratta, P, La Bella, V, Le Ber, I, Van Langenhove, T, Lattante, S, Lee, Y-C, Malaspina, A, Meininger, V, Millecamps, S, Orrell, R, Rademakers, R, Robberecht, W, Rouleau, G, Ross, OA, Salachas, F, Sidle, K, Smith, BN, Soong, B-W, Sorarù, G, Stevanin, G, Kabashi, E, Troakes, C, Van Broeckhoven, C, Veldink, JH, Van Den Berg, LH, Shaw, CE, Powell, JF & Al-Chalabi, A 2017, 'ATXN2 trinucleotide repeat length correlates with risk of ALS', Neurobiology of Aging, vol. 51, pagg. N/A-N/A. https://doi.org/10.1016/j.neurobiolaging.2016.11.010

TY - JOUR

T1 - ATXN2 trinucleotide repeat length correlates with risk of ALS

AU - Sproviero, William

AU - Shatunov, Aleksey

AU - Stahl, Daniel

AU - Shoai, Maryam

AU - Van Rheenen, Wouter

AU - Jones, Ashley R.

AU - Al-Sarraj, Safa

AU - Andersen, Peter M.

AU - Bonini, Nancy M.

AU - Conforti, Francesca L.

AU - Van Damme, Philip

AU - Daoud, Hussein

AU - Del Mar Amador, Maria

AU - Fogh, Isabella

AU - Forzan, Monica

AU - Gaastra, Ben

AU - Gellera, Cinzia

AU - Gitler, Aaron D.

AU - Hardy, John

AU - Fratta, Pietro

AU - La Bella, Vincenzo

AU - Le Ber, Isabelle

AU - Van Langenhove, Tim

AU - Lattante, Serena

AU - Lee, Yi-Chung

AU - Malaspina, Andrea

AU - Meininger, Vincent

AU - Millecamps, Stéphanie

AU - Orrell, Richard

AU - Rademakers, Rosa

AU - Robberecht, Wim

AU - Rouleau, Guy

AU - Ross, Owen A.

AU - Salachas, Francois

AU - Sidle, Katie

AU - Smith, Bradley N.

AU - Soong, Bing-Wen

AU - Sorarù, Gianni

AU - Stevanin, Giovanni

AU - Kabashi, Edor

AU - Troakes, Claire

AU - Van Broeckhoven, Christine

AU - Veldink, Jan H.

AU - Van Den Berg, Leonard H.

AU - Shaw, Christopher E.

AU - Powell, John F.

AU - Al-Chalabi, Ammar

PY - 2017

Y1 - 2017

N2 - We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10-18), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R2 = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.

AB - We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10-18), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R2 = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.

KW - ALS

KW - ATXN2

KW - Age of onset

KW - Amyotrophic lateral sclerosis

KW - CAG

KW - Expansion

KW - Exponential risk

KW - Intermediate expansion

KW - Risk

KW - SCA2

KW - Trinucleotide repeat

KW - Triplet

KW - ALS

KW - ATXN2

KW - Age of onset

KW - Amyotrophic lateral sclerosis

KW - CAG

KW - Expansion

KW - Exponential risk

KW - Intermediate expansion

KW - Risk

KW - SCA2

KW - Trinucleotide repeat

KW - Triplet

UR - http://hdl.handle.net/10807/91793

U2 - 10.1016/j.neurobiolaging.2016.11.010

DO - 10.1016/j.neurobiolaging.2016.11.010

M3 - Article

SN - 0197-4580

VL - 51

SP - N/A-N/A

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

ATXN2 trinucleotide repeat length correlates with risk of ALS

Abstract

Keywords

Accesso al documento

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