Large-scale screening in sporadic amyotrophic lateral sclerosis identifies genetic modifiers in C9orf72 repeat carriers

Neurobiology of Aging
Annelot M DekkerMichael A van Es

Abstract

Sporadic amyotrophic lateral sclerosis (ALS) is considered to be a complex disease with multiple genetic risk factors contributing to the pathogenesis. Identification of genetic risk factors that co-occur frequently could provide relevant insight into underlying mechanisms of motor neuron degeneration. To dissect the genetic architecture of sporadic ALS, we undertook a large sequencing study in 755 apparently sporadic ALS cases and 959 controls, analyzing 10 ALS genes: SOD1, C9orf72, TARDBP, FUS, ANG, CHMP2B, ATXN2, NIPA1, SMN1, and UNC13A. We observed sporadic cases with multiple genetic risk variants in 4.1% compared with 1.3% in controls. The overall difference was not in excess of what is to be expected by chance (binomial test, p = 0.59). We did, however, observe a higher frequency than expected of C9orf72 repeat carriers with co-occurring susceptibility variants (ATXN2, NIPA1, and SMN1; p = 0.001), which is mainly because of the co-occurrence of NIPA1 repeats in 15% of C9orf72 repeat carriers (p = 0.006).

References

Sep 26, 2003·American Journal of Human Genetics·Shirley RainierJohn K Fink
Aug 23, 2005·Proteins·Leonid M ShinchukDaniel A Kirschner
Mar 10, 2009·Neurobiology of Disease·C Messaed, G A Rouleau
Dec 8, 2009·Journal of Neurology, Neurosurgery, and Psychiatry·Michael A van EsP M Andersen
Dec 25, 2009·Neurobiology of Aging·Nicola TicozziJohn E Landers
Feb 10, 2010·Archives of Neurology·Ewout J N GroenLeonard H van den Berg
Aug 6, 2010·Human Molecular Genetics·Hylke M BlauwLeonard H van den Berg
Nov 5, 2010·Journal of Neurology, Neurosurgery, and Psychiatry·Susan ByrneOrla Hardiman
May 31, 2011·Journal of Neurology, Neurosurgery, and Psychiatry·Mark H B HuismanLeonard H van den Berg
Jun 28, 2011·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Christina M LillAmmar Al-Chalabi
Aug 19, 2011·Human Heredity·Ammar Al-Chalabi, Cathryn M Lewis
Nov 29, 2011·Neurobiology of Aging·Frank P DiekstraJan H Veldink
Dec 23, 2011·Annals of Neurology·Michael A van EsLeonard H van den Berg
Feb 11, 2012·Neurology·H M BlauwL H van den Berg
Mar 2, 2012·Human Molecular Genetics·Hylke M BlauwLeonard H van den Berg
Mar 31, 2012·Neurobiology of Aging·Raffaele FerrariParastoo Momeni
May 3, 2012·Journal of Neurology, Neurosurgery, and Psychiatry·Adriano ChiòUNKNOWN SARDINIALS Consortium
May 31, 2012·Human Molecular Genetics·Marka van BlitterswijkLeonard H van den Berg
Jun 9, 2012·Neurobiology of Aging·Perry T C van DoormaalLeonard H van den Berg
Jul 31, 2012·Neurology·Wouter van RheenenLeonard H van den Berg
Aug 11, 2012·Neurobiology of Aging·Marka van BlitterswijkLeonard H van den Berg
Aug 16, 2012·Alzheimer Disease and Associated Disorders·Anna-Lotta KaivorinneAnne M Remes
Nov 17, 2012·PloS One·Marka van BlitterswijkLeonard H van den Berg
Feb 16, 2013·Brain : a Journal of Neurology·Suzanne LesageUNKNOWN French Parkinson’s Disease Genetics Study Group
Apr 5, 2013·Bipolar Disorders·Miriam H MeislerMelvin G McInnis
Jun 12, 2013·PloS One·Olubunmi AbelAmmar Al-Chalabi
Jul 25, 2013·Journal of Medical Genetics·Kevin P KennaOrla Hardiman
Sep 13, 2013·Neurology·Marka van BlitterswijkRosa Rademakers
Nov 30, 2013·Neuropathology and Applied Neurobiology·Tammaryn LashleyTamas Revesz
May 2, 2014·Experimental Neurology·Claire S LeblondGuy A Rouleau
May 29, 2014·Neurobiology of Aging·Marka van BlitterswijkRosa Rademakers
Aug 8, 2014·Neurology·Serena LattanteUNKNOWN French Research Network on FTD and FTD-ALS
Sep 7, 2014·Biochimica Et Biophysica Acta·Senda Ajroud-Driss, Teepu Siddique
Sep 23, 2014·Molecular Neurodegeneration·Marka van BlitterswijkRosa Rademakers

❮ Previous
Next ❯

Citations

Oct 29, 2017·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Sali M K FarhanMichael J Strong
Aug 19, 2016·Current Opinion in Neurology·Matthew A White, Jemeen Sreedharan
Jun 20, 2019·PloS One·Gabriel Rodrigues Coutinho PereiraJoelma Freire De Mesquita
Jul 10, 2019·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Lucia CorradoSandra D'Alfonso
Mar 26, 2019·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Ashley CrookDominic B Rowe
Apr 23, 2016·Journal of Alzheimer's Disease : JAD·Shan-Shan TangJin-Tai Yu
Nov 18, 2021·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration

❮ Previous
Next ❯

Related Concepts

Related Feeds

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.

ALS: Phenotypes

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized phenotypically by progressive muscle weakness. Clinical phenotypes of ALS can be classified based on the pattern, level, and area of onset (e.g. bulbar, cervical, lumbar). Here is the latest research investigating phenotypes of ALS.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

ALS & FTD: TDP-43

TAR DNA-binding protein 43 (TDP-43) is a pathological protein identified in sporadic Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Here are the latest discoveries pertaining to TDP-43 and these diseases.