Evidence for genetic basis of multiple sclerosis

被引:280
作者
Sadovnick, AD
Ebers, GC
Dyment, DA
Risch, NJ
Bulman, D
Rice, GPA
Hashimoto, SA
Paty, D
Oger, JJF
Metz, L
Bell, R
Warren, S
Hader, W
Auty, T
Nath, A
Gray, T
OConner, P
Nelson, R
Freedman, M
Brunet, D
Paulseth, R
Francis, G
Duquette, P
Murray, TJ
Bahn, V
PrysePhillips, W
机构
[1] UNIV WESTERN ONTARIO,DEPT CLIN NEUROL SCI,LONDON,ON,CANADA
[2] STANFORD UNIV,SCH MED,DEPT GENET,STANFORD,CA
[3] MONTREAL NEUROL INST,MONTREAL,PQ,CANADA
[4] HOP NOTRE DAME DE BON SECOURS,MONTREAL,PQ,CANADA
关键词
D O I
10.1016/S0140-6736(96)90807-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 is 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% far 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 full-sib 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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页码:1728 / 1730
页数:3
相关论文
共 30 条
[1]   MULTIPLE SCLEROSIS IN ISRAEL - PREVALENCE AMONG IMMIGRANTS AND NATIVE INHABITANTS [J].
ALTER, M ;
HALPERN, L ;
BORNSTEIN, B ;
KURLAND, LT ;
SILBERSTEIN, J ;
LEIBOWITZ, U ;
TIKVA, P .
ARCHIVES OF NEUROLOGY, 1962, 7 (04) :253-&
[2]   AGE OF ONSET IN SIBLINGS CONCORDANT FOR MULTIPLE-SCLEROSIS [J].
BULMAN, DE ;
SADOVNICK, AD ;
EBERS, GC .
BRAIN, 1991, 114 :937-950
[4]   EVIDENCE FOR LOWER SUSCEPTIBILITY TO MULTIPLE-SCLEROSIS IN JAPANESE-AMERICANS [J].
DETELS, R ;
VISSCHER, BR ;
MALMGREN, RM ;
COULSON, AH ;
LUCIA, MV ;
DUDLEY, JP .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 1977, 105 (04) :303-310
[5]   A POPULATION-BASED STUDY OF MULTIPLE-SCLEROSIS IN TWINS [J].
EBERS, GC ;
BULMAN, DE ;
SADOVNICK, AD ;
PATY, DW ;
WARREN, S ;
HADER, W ;
MURRAY, TJ ;
SELAND, TP ;
DUQUETTE, P ;
GREY, T ;
NELSON, R ;
NICOLLE, M ;
BRUNET, D .
NEW ENGLAND JOURNAL OF MEDICINE, 1986, 315 (26) :1638-1642
[6]   A GENETIC-BASIS FOR FAMILIAL AGGREGATION IN MULTIPLE-SCLEROSIS [J].
EBERS, GC ;
SADOVNICK, AD ;
RISCH, NJ ;
BULMAN, D ;
RICE, GPA ;
HASHIMOTO, SA ;
PATY, D ;
OGER, JJF ;
METZ, L ;
BELL, R ;
WARREN, S ;
HADER, W ;
AUTY, T ;
NATH, A ;
GRAY, T ;
OCONNOR, P ;
NELSON, R ;
FREEDMAN, M ;
BRUNET, D ;
PAULSETH, R ;
FRANCIS, G ;
DUQUETTE, P ;
MURRAY, TJ ;
BAHN, V ;
PRYSEPHILLIPS, W .
NATURE, 1995, 377 (6545) :150-151
[7]   ASSOCIATION STUDIES IN MULTIPLE-SCLEROSIS [J].
EBERS, GC ;
SADOVNICK, AD .
JOURNAL OF NEUROIMMUNOLOGY, 1994, 53 (02) :117-122
[8]   CONJUGAL MULTIPLE-SCLEROSIS - A CLINICAL AND LABORATORY STUDY [J].
FINELLI, PF .
NEUROLOGY, 1991, 41 (08) :1320-1321
[9]   CONJUGAL MULTIPLE-SCLEROSIS - IMMUNOGENETIC CHARACTERIZATION AND ANALYSIS OF T-CELL AND B-CELL REACTIVITY TO MYELIN PROTEINS [J].
FREDRIKSON, S ;
MICHELSBERG, J ;
HILLERT, J ;
WANG, Z ;
SUN, JB ;
OLERUP, O ;
OLSSON, T ;
LINK, H .
NEUROLOGY, 1992, 42 (03) :577-582
[10]   A STUDY OF BIRTH-ORDER AND MULTIPLE-SCLEROSIS IN MULTIPLEX FAMILIES [J].
GAUDET, JPC ;
HASHIMOTO, L ;
SADOVNICK, AD ;
EBERS, GC .
NEUROEPIDEMIOLOGY, 1995, 14 (04) :188-192