PMID- 2731721
OWN - NLM
STAT- MEDLINE
DCOM- 19890725
LR  - 20101118
IS  - 0741-0395 (Print)
IS  - 0741-0395 (Linking)
VI  - 6
IP  - 1
DP  - 1989
TI  - Linkage analysis and genetic models for IDDM.
PG  - 83-8
AB  - The multiplex insulin-dependent diabetes mellitus (IDDM) families have been 
      examined for linkage with the human leukocyte antigen (HLA), Gm, Km, and insulin 
      loci. For the last three, no evidence of linkage (as measured by haplotype 
      sharing in affected siblings) was found. For HLA, strong evidence of linkage was 
      demonstrated, as expected from previous studies of both haplotype sharing and HLA 
      association. The haplotype sharing in affected siblings from this and previous 
      studies would explain a relative risk of about 3.7 in the sibling of an affected 
      individual (95% confidence limits 2.8 to 5.4), considerably less than the values 
      of 10-15 given by epidemiological studies. This discrepancy may be explained by 
      other predisposing genes unlinked to HLA, or be due to common environmental 
      factors. Analysis conditional on the affection status of all individuals, and on 
      the parental HLA haplotypes clearly rejects both a dominant and recessive mode of 
      inheritance in favor of a two-allele model with a reduced risk for heterozygotes, 
      and provides some support for a three-allele model. Some evidence of age effects 
      was found; in particular there was some suggestion of greater haplotype sharing 
      in siblings both affected at a young age, and there was some suggestion that 
      individuals with the predisposing HLA-DR3/DR4, DR3/DRx, and DR4/DRx genotypes 
      were affected at a younger age. These results may be diagnostic artifacts, 
      however, and need investigation in future studies.
FAU - Easton, D F
AU  - Easton DF
AD  - Section of Epidemiology, Institute of Cancer Research, Sutton, Surrey, England.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genet Epidemiol
JT  - Genetic epidemiology
JID - 8411723
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Child
MH  - Diabetes Mellitus, Type 1/epidemiology/*genetics
MH  - Diseases in Twins
MH  - *Genetic Linkage
MH  - HLA-DR Antigens/genetics
MH  - Humans
MH  - *Models, Genetic
MH  - Risk Factors
EDAT- 1989/01/01 00:00
MHDA- 1989/01/01 00:01
CRDT- 1989/01/01 00:00
PHST- 1989/01/01 00:00 [pubmed]
PHST- 1989/01/01 00:01 [medline]
PHST- 1989/01/01 00:00 [entrez]
AID - 10.1002/gepi.1370060116 [doi]
PST - ppublish
SO  - Genet Epidemiol. 1989;6(1):83-8. doi: 10.1002/gepi.1370060116.