ATXN2 trinucleotide repeat length correlates with risk of ALS

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

Risultato della ricerca: Article

21 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 originaleEnglish
pagine (da-a)178-178.e9
Numero di pagine9
RivistaNeurobiology of Aging
Volume51
Stato di pubblicazionePublished - 2017

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Trinucleotide Repeats
Amyotrophic Lateral Sclerosis
Trinucleotide Repeat Expansion
Alleles
Age of Onset
Case-Control Studies
PubMed
Meta-Analysis
Odds Ratio
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cita questo

La Bella, V., Kabashi, E., Fratta, P., Fogh, I., Daoud, H., Forzan, M., ... Lee, Y-C. (2017). ATXN2 trinucleotide repeat length correlates with risk of ALS. Neurobiology of Aging, 51, 178-178.e9.

ATXN2 trinucleotide repeat length correlates with risk of ALS. / La Bella, Vincenzo; Kabashi, Edor; Fratta, Pietro; Fogh, Isabella; Daoud, Hussein; Forzan, Monica; Van Langenhove, Tim; Lattante, Serena; Shaw, Christopher E.; Sorarù, Gianni; Van Rheenen, Wouter; Sproviero, William; Jones, Ashley R.; Shoai, Maryam; Shatunov, Aleksey; Andersen, Peter M.; Veldink, Jan H.; Hardy, John; Stevanin, Giovanni; Van Den Berg, Leonard H.; Stahl, Daniel; Del Mar Amador, Maria; Gaastra, Ben; Rouleau, Guy; Gitler, Aaron D.; Al-Sarraj, Safa; Rademakers, Rosa; Le Ber, Isabelle; Sidle, Katie; Malaspina, Andrea; Ross, Owen A.; Conforti, Francesca L.; Al-Chalabi, Ammar; Gellera, Cinzia; Robberecht, Wim; Orrell, Richard; Bonini, Nancy M.; Soong, Bing-Wen; Meininger, Vincent; Van Damme, Philip; Van Broeckhoven, Christine; Powell, John F.; Smith, Bradley N.; Troakes, Claire; Salachas, Francois; Millecamps, Stéphanie; Lee, Yi-Chung.

In: Neurobiology of Aging, Vol. 51, 2017, pag. 178-178.e9.

Risultato della ricerca: Article

La Bella, V, Kabashi, E, Fratta, P, Fogh, I, Daoud, H, Forzan, M, Van Langenhove, T, Lattante, S, Shaw, CE, Sorarù, G, Van Rheenen, W, Sproviero, W, Jones, AR, Shoai, M, Shatunov, A, Andersen, PM, Veldink, JH, Hardy, J, Stevanin, G, Van Den Berg, LH, Stahl, D, Del Mar Amador, M, Gaastra, B, Rouleau, G, Gitler, AD, Al-Sarraj, S, Rademakers, R, Le Ber, I, Sidle, K, Malaspina, A, Ross, OA, Conforti, FL, Al-Chalabi, A, Gellera, C, Robberecht, W, Orrell, R, Bonini, NM, Soong, B-W, Meininger, V, Van Damme, P, Van Broeckhoven, C, Powell, JF, Smith, BN, Troakes, C, Salachas, F, Millecamps, S & Lee, Y-C 2017, 'ATXN2 trinucleotide repeat length correlates with risk of ALS', Neurobiology of Aging, vol. 51, pagg. 178-178.e9.
La Bella V, Kabashi E, Fratta P, Fogh I, Daoud H, Forzan M e altri. ATXN2 trinucleotide repeat length correlates with risk of ALS. Neurobiology of Aging. 2017;51:178-178.e9.
La Bella, Vincenzo ; Kabashi, Edor ; Fratta, Pietro ; Fogh, Isabella ; Daoud, Hussein ; Forzan, Monica ; Van Langenhove, Tim ; Lattante, Serena ; Shaw, Christopher E. ; Sorarù, Gianni ; Van Rheenen, Wouter ; Sproviero, William ; Jones, Ashley R. ; Shoai, Maryam ; Shatunov, Aleksey ; Andersen, Peter M. ; Veldink, Jan H. ; Hardy, John ; Stevanin, Giovanni ; Van Den Berg, Leonard H. ; Stahl, Daniel ; Del Mar Amador, Maria ; Gaastra, Ben ; Rouleau, Guy ; Gitler, Aaron D. ; Al-Sarraj, Safa ; Rademakers, Rosa ; Le Ber, Isabelle ; Sidle, Katie ; Malaspina, Andrea ; Ross, Owen A. ; Conforti, Francesca L. ; Al-Chalabi, Ammar ; Gellera, Cinzia ; Robberecht, Wim ; Orrell, Richard ; Bonini, Nancy M. ; Soong, Bing-Wen ; Meininger, Vincent ; Van Damme, Philip ; Van Broeckhoven, Christine ; Powell, John F. ; Smith, Bradley N. ; Troakes, Claire ; Salachas, Francois ; Millecamps, Stéphanie ; Lee, Yi-Chung. / ATXN2 trinucleotide repeat length correlates with risk of ALS. In: Neurobiology of Aging. 2017 ; Vol. 51. pagg. 178-178.e9.
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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, Aging, Amyotrophic lateral sclerosis, CAG, Developmental Biology, Expansion, Exponential risk, Geriatrics and Gerontology, Intermediate expansion, Neurology (clinical), Neuroscience (all), Risk, SCA2, Trinucleotide repeat, Triplet",
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TY - JOUR

T1 - ATXN2 trinucleotide repeat length correlates with risk of ALS

AU - La Bella, Vincenzo

AU - Kabashi, Edor

AU - Fratta, Pietro

AU - Fogh, Isabella

AU - Daoud, Hussein

AU - Forzan, Monica

AU - Van Langenhove, Tim

AU - Lattante, Serena

AU - Shaw, Christopher E.

AU - Sorarù, Gianni

AU - Van Rheenen, Wouter

AU - Sproviero, William

AU - Jones, Ashley R.

AU - Shoai, Maryam

AU - Shatunov, Aleksey

AU - Andersen, Peter M.

AU - Veldink, Jan H.

AU - Hardy, John

AU - Stevanin, Giovanni

AU - Van Den Berg, Leonard H.

AU - Stahl, Daniel

AU - Del Mar Amador, Maria

AU - Gaastra, Ben

AU - Rouleau, Guy

AU - Gitler, Aaron D.

AU - Al-Sarraj, Safa

AU - Rademakers, Rosa

AU - Le Ber, Isabelle

AU - Sidle, Katie

AU - Malaspina, Andrea

AU - Ross, Owen A.

AU - Conforti, Francesca L.

AU - Al-Chalabi, Ammar

AU - Gellera, Cinzia

AU - Robberecht, Wim

AU - Orrell, Richard

AU - Bonini, Nancy M.

AU - Soong, Bing-Wen

AU - Meininger, Vincent

AU - Van Damme, Philip

AU - Van Broeckhoven, Christine

AU - Powell, John F.

AU - Smith, Bradley N.

AU - Troakes, Claire

AU - Salachas, Francois

AU - Millecamps, Stéphanie

AU - Lee, Yi-Chung

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 - Aging

KW - Amyotrophic lateral sclerosis

KW - CAG

KW - Developmental Biology

KW - Expansion

KW - Exponential risk

KW - Geriatrics and Gerontology

KW - Intermediate expansion

KW - Neurology (clinical)

KW - Neuroscience (all)

KW - Risk

KW - SCA2

KW - Trinucleotide repeat

KW - Triplet

UR - http://hdl.handle.net/10447/226823

UR - http://www.elsevier.com/locate/neuaging

M3 - Article

VL - 51

SP - 178-178.e9

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -