OBJECTIVES: To investigate the cause of sporadic motor neuron disease (MND) by twin study, so allowing (1) estimation of the genetic contribution, and (2) collection of matched pairs for a case-control study of possible environmental factors. METHODS: 10872 death certificates bearing the diagnosis MND were collected from 1979 to 1989 inclusive. Inspection of individual birth entries allowed identification of potential twins. The status of each co-twin was determined and contact made through the National Health Service Central Register (NHS-CR) and their general practitioner (GP). The diagnosis of MND was verified via the co-twin and relatives, and medical records where available. Zygosity was assessed using a recognised questionnaire. Details concerning environmental exposures and health were gathered by interview of cotwin and relatives using a semistructured questionnaire. Heritability (h2) of MND was estimated, and the environmental information was analysed by conditional logistic regression modelling. RESULTS: Seventy seven probands were identified, of whom 26 were monozygotic and 51 dizygotic. Four monozygotic probands were concordant, but two probands came from a family known to have familial MND. The estimated heritability was between 0.38 and 0.85. Most environmental risk factors were not significant. Regular vehicle maintenance (odds ratio (OR) = 7.0; 95% confidence interval (95% CI) 1.3-89.9) and occupational paint usage (OR = 3.75; 95% CI 1.0-17.1), however, occurred significantly more often in the affected cases. CONCLUSIONS: This "death discordant" method for twin collection has proved to be viable, and has allowed the ascertainment of a large population sample in a rare disease. The genetic role in sporadic MND is substantial, and higher than expected. Exposure to industrial chemicals, particularly constituents of petrochemicals and paints, may contribute to the aetiology of MND.
OBJECTIVES: To investigate the cause of sporadic motor neuron disease (MND) by twin study, so allowing (1) estimation of the genetic contribution, and (2) collection of matched pairs for a case-control study of possible environmental factors. METHODS: 10872 death certificates bearing the diagnosis MND were collected from 1979 to 1989 inclusive. Inspection of individual birth entries allowed identification of potential twins. The status of each co-twin was determined and contact made through the National Health Service Central Register (NHS-CR) and their general practitioner (GP). The diagnosis of MND was verified via the co-twin and relatives, and medical records where available. Zygosity was assessed using a recognised questionnaire. Details concerning environmental exposures and health were gathered by interview of cotwin and relatives using a semistructured questionnaire. Heritability (h2) of MND was estimated, and the environmental information was analysed by conditional logistic regression modelling. RESULTS: Seventy seven probands were identified, of whom 26 were monozygotic and 51 dizygotic. Four monozygotic probands were concordant, but two probands came from a family known to have familial MND. The estimated heritability was between 0.38 and 0.85. Most environmental risk factors were not significant. Regular vehicle maintenance (odds ratio (OR) = 7.0; 95% confidence interval (95% CI) 1.3-89.9) and occupational paint usage (OR = 3.75; 95% CI 1.0-17.1), however, occurred significantly more often in the affected cases. CONCLUSIONS: This "death discordant" method for twin collection has proved to be viable, and has allowed the ascertainment of a large population sample in a rare disease. The genetic role in sporadic MND is substantial, and higher than expected. Exposure to industrial chemicals, particularly constituents of petrochemicals and paints, may contribute to the aetiology of MND.
Authors: A Al-Chalabi; F Fang; M F Hanby; P N Leigh; C E Shaw; W Ye; F Rijsdijk Journal: J Neurol Neurosurg Psychiatry Date: 2010-09-22 Impact factor: 13.654
Authors: Adriano Chiò; Jennifer C Schymick; Gabriella Restagno; Sonja W Scholz; Federica Lombardo; Shiao-Lin Lai; Gabriele Mora; Hon-Chung Fung; Angela Britton; Sampath Arepalli; J Raphael Gibbs; Michael Nalls; Stephen Berger; Lydia Coulter Kwee; Eugene Z Oddone; Jinhui Ding; Cynthia Crews; Ian Rafferty; Nicole Washecka; Dena Hernandez; Luigi Ferrucci; Stefania Bandinelli; Jack Guralnik; Fabio Macciardi; Federica Torri; Sara Lupoli; Stephen J Chanock; Gilles Thomas; David J Hunter; Christian Gieger; H Erich Wichmann; Andrea Calvo; Roberto Mutani; Stefania Battistini; Fabio Giannini; Claudia Caponnetto; Giovanni Luigi Mancardi; Vincenzo La Bella; Francesca Valentino; Maria Rosaria Monsurrò; Gioacchino Tedeschi; Kalliopi Marinou; Mario Sabatelli; Amelia Conte; Jessica Mandrioli; Patrizia Sola; Fabrizio Salvi; Ilaria Bartolomei; Gabriele Siciliano; Cecilia Carlesi; Richard W Orrell; Kevin Talbot; Zachary Simmons; James Connor; Erik P Pioro; Travis Dunkley; Dietrich A Stephan; Dalia Kasperaviciute; Elizabeth M Fisher; Sibylle Jabonka; Michael Sendtner; Marcus Beck; Lucie Bruijn; Jeffrey Rothstein; Silke Schmidt; Andrew Singleton; John Hardy; Bryan J Traynor Journal: Hum Mol Genet Date: 2009-02-04 Impact factor: 6.150
Authors: John E Landers; Lijia Shi; Ting-Jan Cho; Jonathan D Glass; Christopher E Shaw; P Nigel Leigh; Frank Diekstra; Meraida Polak; Ildefonso Rodriguez-Leyva; Stephan Niemann; Bryan J Traynor; Diane McKenna-Yasek; Peter C Sapp; Ammar Al-Chalabi; Anne-Marie A Wills; Robert H Brown Journal: Amyotroph Lateral Scler Date: 2008-10
Authors: Laura E Cox; Laura Ferraiuolo; Emily F Goodall; Paul R Heath; Adrian Higginbottom; Heather Mortiboys; Hannah C Hollinger; Judith A Hartley; Alice Brockington; Christine E Burness; Karen E Morrison; Stephen B Wharton; Andrew J Grierson; Paul G Ince; Janine Kirby; Pamela J Shaw Journal: PLoS One Date: 2010-03-24 Impact factor: 3.240