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Both genetic and environmental factors contribute to multiple sclerosis, the most common neurodegenerative disorder with onset in young adults. The objective of the current study is, based on the hypothesis that environmentally predisposed individuals are at risk for multiple sclerosis, to investigate whether they also carry genetic variants within the vitamin D machinery. Using medical files and DNA samples from 583 trios (a patient and both parents) of the French Multiple Sclerosis Genetics Group as well as data from the French Statistics Bureau, we aimed to assess whether: (1) a seasonality of birth was observed in French multiple sclerosis patients; (2) three single nucleotide polymorphisms within the promoter region of the vitamin D receptor were associated with multiple sclerosis susceptibility; and (3) the combination of a high risk month of birth and vitamin D receptor polymorphisms were correlated to multiple sclerosis incidence. We observed a significantly reduced number of individuals born in November who were later diagnosed as multiple sclerosis patients. However, we found no association between the three studied vitamin D receptor polymorphisms and multiple sclerosis. In conclusion, our data suggest that high levels of vitamin D during the third trimester of pregnancy could be a protective factor for multiple sclerosis.

Measuring inbreeding and its consequences on fitness is central for many areas in biology including human genetics and the conservation of endangered species. However, there is no consensus on the best method, neither for quantification of inbreeding itself nor for the model to estimate its effect on specific traits. We simulated traits based on simulated genomes from a large pedigree and empirical whole-genome sequences of human data from populations with various sizes and structures (from the 1,000 Genomes project). We compare the ability of various inbreeding coefficients (F) to quantify the strength of inbreeding depression: allele-sharing, two versions of the correlation of uniting gametes which differ in the weight they attribute to each locus and two identical-by-descent segments-based estimators. We also compare two models: the standard linear model and a linear mixed model (LMM) including a genetic relatedness matrix (GRM) as random effect to account for the nonindependence of observations. We find LMMs give better results in scenarios with population or family structure. Within the LMM, we compare three different GRMs and show that in homogeneous populations, there is little difference among the different F and GRM for inbreeding depression quantification. However, as soon as a strong population or family structure is present, the strength of inbreeding depression can be most efficiently estimated only if i) the phenotypes are regressed on F based on a weighted version of the correlation of uniting gametes, giving more weight to common alleles and ii) with the GRM obtained from an allele-sharing relatedness estimator. [ABSTRACT FROM AUTHOR]

Corrigendum to Season of birth and not vitamin D receptor promoter polymorphisms is a risk factor for multiple sclerosis by DA Fernandes de Abreu, MC Babron I, C Rebeix, J Fontenille, D Yaouanq, B Brassat, F Fontaine, F Clerget-Darpoux, F Jehan and Feron. Mult Scler 2009; 15: 1146–1152 [DOI: 10.1177/1352458509106780] [ABSTRACT FROM AUTHOR]

Introduction: Many studies have shown that people born in the spring are at a higher risk of developing multiple sclerosis (MS). This may be associated with lower levels of sun exposure, and consequently, lower levels of vitamin D3 during pregnancy. However, these relationships have not been verified thus far in any countries in Central Europe. Objective: The aim of our study was to determine the frequency distribution of births for each calendar month in patients suffering from MS in Poland. Methods: We analyzed data for 2574 patients diagnosed with MS (1758 women, 816 men) living in Poland for an extended period. We added corrections resulting from the frequency distribution of births for the years in which the patients were born. We applied the Hewitt test for seasonality with Rogerson modification for 3-, 4-, or 6-month pulses or periods. Moreover, we examined the average number hours of sunshine in every month of the year. Results: The rank-sums for successive 3- and 4-month segments indicated the period from September to December and from October to December as having a significantly lower incidence (p = 0.027 and p = 0.054, respectively). We did not find a correlation between with hours of sunshine in the first trimester of pregnancy, the child’s birth month, and the child developing MS. Conclusions: We were able to confirm a seasonal variation in the risk of MS in Poland. However, these findings did not correlate with hours of sunshine during the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]