Elsevier

The Lancet

Volume 347, Issue 9017, 22 June 1996, Pages 1728-1730
The Lancet

Articles
Evidence for genetic basis of multiple sclerosis

https://doi.org/10.1016/S0140-6736(96)90807-7Get rights and content

Abstract

Summary

Background Increased familial risks in multiple sclerosis (MS) range from 300-fold for monozygotic twins to 20-40-fold for biological first-degree relatives, suggesting a genetic influence. Yet if one identical twin has MS the other usually will not. One way of sorting out the contributions of genes and environment is to study half-sibs.

Methods In a Canadian population-based sample of 16 000 MS cases seen at 14 regional MS clinics one half-sib (or more) was reported by 939 index cases. By interview we elicited information on family structure and an illness in half-sibs and any full brothers or sisters.

Findings The age-adjusted MS rate in the 1839 half-sibs of these index cases was 1·32% compared with 3·46% for the 1395 full sibs of the same cases (p<0·001; likelihood ratio test). There were no significant differences in risk for maternal versus paternal half-sibs (1·42% vs 1·19%) or for those raised together versus those raised apart from the index case (1·17% vs 1·47%).

Interpretation Besides demonstrating the power and the feasiblity of using half-sib studies to throw light on the aetiology of complex disorders, our findings show that a shared environment does not account for familial risk in MS and that maternal effects (such as intrauterine and perinatal factors, breastfeeding, and genomic imprinting) have no demonstrable effect on familial risk. Halving the number of potentially contributory genes (by comparing fullsib and half-sib rates) lowers the risk of MS by a factor of 2·62, an observation consistent with a polygenic hypothesis.

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      A Canadian study confirmed a pattern of increased familial risk for this autoimmune disease (Sadovnick et al., 1996). According to their findings, the risk for developing MS is 300-fold greater in monozygotic twins when one sibling is affected and at least 20-fold greater in individuals with first-degree family members suffering from MS (Sadovnick et al., 1996). Of note, the disease is closely linked to certain major histocompatibility complexes including HLA-DRB1.

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