Genetic and Environmental Susceptibility to Multiple Sclerosis
Notice bibliographique
Résumé
OBJECTIVE: To explore the nature and basis of environmental and genetic susceptibility to multiple sclerosis (MS). BACKGROUND Susceptibility to multiple sclerosis (MS) is complex but clearly involves both environmental events and genetic factors. Certain epidemiological observations regarding MS (e.g., proportion of women among MS patients, population-prevalence of MS, impact of birth-month and migration patterns on the likelihood of MS, recurrence-risks for MS in siblings and twins, and time-dependent changes in MS-prevalence and the female to male sex-ratio) are well-established. DESIGN/METHODS: We define the “genetically-susceptible” subset (G) to include everyone with any non-zero life-time chance of developing MS. Individuals who have no chance of developing MS, regardless of their environmental experiences, belong to the mutually exclusive “non-susceptible” subset (G–). We consider the implications that these well-established epidemiological observations have regarding the genetic and environmental basis of susceptibility to MS. In addition, we use the change in the female to male sex ratio, observed over a 35-year interval in Canada, to construct the response curves relating an increasing likelihood of MS to an increasing probability of a susceptible individual experiencing an environmental exposure sufficient to cause MS. RESULTS: Environmental susceptibility to MS requires at least three different events – one occurring during the intrauterine or early post-natal period, another during childhood or adolescence, and a third (or more) many years later. Vitamin D deficiency and Epstein-Barr viral infections are likely involved. Moreover, we demonstrate that only a very small fraction of the general populations throughout Europe and North America is susceptible to MS. The vast majority of individuals in these populations has no chance whatsoever of developing MS, regardless of their environmental experiences. Even among carriers of the HLA-DRB1*15:01~HLA-DQB1*06:02~a1 haplotype, only a small minority can possibly be members the (G) subset. Also, despite the preponderance of women among MS patients, compared to men, women are less likely to be susceptible and have a higher environmental threshold for developing MS. Nevertheless, the penetrance of MS in susceptible women is substantially greater than it is in men. Moreover, MS-probability in susceptible individuals increases with an increasing likelihood of a sufficient environmental exposure, especially among women. However, these response-curves plateau at under 50% for women and at a significantly lower level for men. CONCLUSIONS: The pathogenesis of MS requires both a genetic predisposition and a suitable environmental exposure. Nevertheless, genetic-susceptibility is rare in the population and requires specific combinations of non-additive genetic risk-factors. By contrast, a sufficient environmental exposure (however many events are involved, whenever these events need to act, and whatever these events might be) is common, currently occurring in, at least, 76% of susceptible individuals. In addition, the environmental response-curves (especially in men) plateau well below 50%, which indicates that disease pathogenesis is partially stochastic.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,021 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,002 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,002 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».