A E Handel1,2, L Handunnetthi1,2, G Giovannoni3, G C Ebers1,2, S V Ramagopalan1,2. 1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford. 2. Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford. 3. Blizard Institute of Cell and Molecular Science, Queen Mary University, and the Department of Neurology, Barts and The London School of Medicine and Dentistry, Queen Mary University London, UK.
Abstract
BACKGROUND: The observation that the incidence of multiple sclerosis (MS) increases further from the equator has prompted considerable interest in the factors that might underlie this latitude gradient. Potential candidates include population frequencies of disease-associated Human Leukocyte Antigen (HLA) alleles which are the major genetic component of MS susceptibility. Ultraviolet (UV) exposure and smoking have also been implicated as key environmental risk factors. METHODS: We used multiple sources of published data on MS prevalence, HLA allele frequencies, UV index and cigarette smoking to assess the contributions of both nature and nurture to the distribution of MS within Europe. RESULTS: We observed that HLA alleles unequivocally interact with a population-wide level to determine disease risk. The UV index and smoking behaviour was also shown to correlate with disease distribution in Europe. For countries with HLA, UV and smoking data, these three factors were shown to account for 75% of the variance in MS prevalence. CONCLUSIONS: Genetic (HLA) and environmental (UV and smoking) risk factors thus interact in a complex manner with each other to determine a large proportion of MS susceptibility within Europe.
BACKGROUND: The observation that the incidence of multiple sclerosis (MS) increases further from the equator has prompted considerable interest in the factors that might underlie this latitude gradient. Potential candidates include population frequencies of disease-associated Human Leukocyte Antigen (HLA) alleles which are the major genetic component of MS susceptibility. Ultraviolet (UV) exposure and smoking have also been implicated as key environmental risk factors. METHODS: We used multiple sources of published data on MS prevalence, HLA allele frequencies, UV index and cigarette smoking to assess the contributions of both nature and nurture to the distribution of MS within Europe. RESULTS: We observed that HLA alleles unequivocally interact with a population-wide level to determine disease risk. The UV index and smoking behaviour was also shown to correlate with disease distribution in Europe. For countries with HLA, UV and smoking data, these three factors were shown to account for 75% of the variance in MS prevalence. CONCLUSIONS: Genetic (HLA) and environmental (UV and smoking) risk factors thus interact in a complex manner with each other to determine a large proportion of MS susceptibility within Europe.
Authors: David Martin; Cristina Pantoja; Ana Fernández Miñán; Christian Valdes-Quezada; Eduardo Moltó; Fuencisla Matesanz; Ozren Bogdanović; Elisa de la Calle-Mustienes; Orlando Domínguez; Leila Taher; Mayra Furlan-Magaril; Antonio Alcina; Susana Cañón; María Fedetz; María A Blasco; Paulo S Pereira; Ivan Ovcharenko; Félix Recillas-Targa; Lluís Montoliu; Miguel Manzanares; Roderic Guigó; Manuel Serrano; Fernando Casares; José Luis Gómez-Skarmeta Journal: Nat Struct Mol Biol Date: 2011-05-22 Impact factor: 15.369
Authors: Adam E Handel; Alexander J Williamson; Giulio Disanto; Lahiru Handunnetthi; Gavin Giovannoni; Sreeram V Ramagopalan Journal: PLoS One Date: 2010-09-01 Impact factor: 3.240
Authors: Adam E Handel; Lynne Jarvis; Ryan McLaughlin; Anastasia Fries; George C Ebers; Sreeram V Ramagopalan Journal: PLoS One Date: 2011-01-27 Impact factor: 3.240