Genetic epidemiology of amyotrophic lateral sclerosis

TLDR: This review presents a tentative classification of the “major” ALS genes and ALS “susceptibility” genes, that may act as susceptibility factors for neurodegeneration in interaction with other genetic or environmental risk factors.

Abstract: Amyotrophic lateral sclerosis (ALS) is a late onset, rapidly progressive and ultimately fatal neurological disorder, caused by the loss of motor neurons in the brain and spinal cord. Familial aggregation of ALS, with an age-dependent but high penetrance, is a major risk factor for ALS. Familial ALS (FALS) is clinically and genetically heterogeneous. Three genes and linkage to four additional gene loci have been identified so far and may either predominantly lead to ALS (ALSI-ALS6) or cause multisystem neurodegeneration with ALS as an occasional symptom (tauopathies, ALS-dementia complex). This review presents a tentative classification of the "major" ALS genes and ALS "susceptibility" genes, that may act as susceptibility factors for neurodegeneration in interaction with other genetic or environmental risk factors. Considering that mutations in ALS genes explain approximately 10% of familial as well as sporadic ALS, and most remaining cases of the discase are thought to result form the interaction of several genes and environmental factors, ALS is a paradigm for multifactorial discases.

Figures

Figure 1. The human motor neuron system

Table 6. Number of ALS cases and controls, and univariable odds ratios for lifestyle

Table 5. Number of ALS cases and controls, and univariable odds ratios for exposure to animals

Table 4. Number of ALS cases and controls, and univariable odds ratios for toxic exposures

Table 3. Co-occurrence of dementia and parkinsonism in the families of 140 pairs of matched ALS patients and controls

Figure 2. Age-specific incidence of amyotrophic lateral sclerosis (ALS) in men and women for Washington State (14), Harris County, Texas (9) and Ireland (10).

Full text

Genetic Epidemiology of Amyotrophic
Lateral Sclerosis
Genetische epidemiologie van
amyotrofische lateraal sclerose
Danielle Fanny Majoor-Krakauer

© Danielle Fanny Majoor-Krakauer, 2005
No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means
without permission of the author. The copyright of the publications remains with the publishers.
ISBN: 90-9019289-1
ACKNOWLEDGEMENT
The study presented in this thesis was conducted at the Neurological Institute, Columbia University Medical
Center and the G.H. Sergievsky Center and Department of Epidemiology, Mailman School of Public Health,
Columbia University, New York, NY, USA.
The work was completed at the department of Clinical Genetics at the Erasmus Medical Center in Rotterdam in
close collaboration with the Department of Epidemiology and Biostastitics of the Erasmus Medical Center.
The study was supported by a grant of the Muscular Dystrophy Association.
Cover and graphical support: T. de Vries Lentsch
Printing: Offsetdrukkerij Haveka B.V., Alblasserdam
Cover: Victor Levasseur “Oceanie”. Paris. 1854. Map shows the Pacific Ocean divided into four regions. 1.
Malaisie, 2. Melanesie or Australia, 3. Polynesia and 4. Micronesie. These four divisions were based upon the
surveys taken by Capt. Dumont D’Urville during his two circumnavigations in 1822-1825 and 1826-1829 during
which he charted the Pacific Islands in great detail. Victor Levasseur, the author of this map, employed a famous
French artist, Raimond Bonheur, to draw the wonderful & fanciful scenes surrounding the map including the
entrance to a harbor depicted in lower right showing a fort high on a bluff and sailing vessels below. From
Levasseur’s “Atlas National Illustre”, published in 1854.

Genetic Epidemiology of Amyotrophic
Lateral Sclerosis
Genetische epidemiologie van amyotrofische
lateraal sclerose
Thesis to obtain the degree of Doctor from the Erasmus University
Rotterdam by command of the rector magnificus
Prof.dr. S.W.J. Lamberts
and according to the decision of the Doctorate Board.
The public defence shall be held on
Wednesday May 18 2005 at 15.45 hrs by
Danielle Fanny Majoor-Krakauer
born in The Hague

Promotiecommissie
Promotoren
Prof.dr. H. Galjaard
Prof.dr. A. Hofman
Overige leden
Prof.dr. R. Ottman
Dr. J.C. van Swieten
Prof.dr. J.H.J. Wokke