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A comparison of three statistical models for IDDM associations with HLA

Graham, J. ; Kockum, I. ; Breslow, N. ; Lernmark, Å LU orcid and Holmberg, E. (1996) In Tissue Antigens 48(1). p.1-14
Abstract

The association between HLA-DQ haplotypes and insulin-dependent diabetes mellitus (IDDM) was studied in 48 children from 44 families ascertained from the high incidence area around Umea, Sweden. Numerous hypotheses have been proposed to explain associations between HLA and IDDM, but comparisons of statistical models based on these hypotheses have not been attempted. The aim of the present study was to compare the goodness-of-fit and predictive abilities among different statistical models. A likelihood-based analysis rather than a conventional analysis based on contingency tables was therefore adopted. We first used parental haplotype information in a conditional likelihood analysis (1) and then compared this analysis with that of an... (More)

The association between HLA-DQ haplotypes and insulin-dependent diabetes mellitus (IDDM) was studied in 48 children from 44 families ascertained from the high incidence area around Umea, Sweden. Numerous hypotheses have been proposed to explain associations between HLA and IDDM, but comparisons of statistical models based on these hypotheses have not been attempted. The aim of the present study was to compare the goodness-of-fit and predictive abilities among different statistical models. A likelihood-based analysis rather than a conventional analysis based on contingency tables was therefore adopted. We first used parental haplotype information in a conditional likelihood analysis (1) and then compared this analysis with that of an unaffected control group which used information on geographically matched controls. Under the analysis conditional on parental haplotype, a statistical model motivated by the hypothesis that the entire DQ heterodimer is involved in IDDM pathogenesis fit the data significantly better and had greater predictive ability than either a model motivated by the explanation that an IDDM gene is linked to DQB1 or that the DQB1 chain itself is involved in IDDM pathogenesis, or a model arising from the hypothesis that single amino acids at codon 57 of DQB1 and codon 52 of DQA1, respectively, confer susceptibility. Under the case-control analysis, the identity of the best-fitting or most predictive statistical model was not as clear, although both approaches to analyzing risk suggested that the single-amino-acids model had significantly poorer fit compared to the remaining two models.

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author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diabetes mellitus, insulin-dependent, Disease susceptibility, Genetic marker, Haplotype, HLA-DQ antigen, Likelihood function, Model, statistical
in
Tissue Antigens
volume
48
issue
1
pages
14 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:0029820687
  • pmid:8864169
ISSN
0001-2815
DOI
10.1111/j.1399-0039.1996.tb02599.x
language
English
LU publication?
no
id
fe62ad58-8c1d-4724-bfc2-557b6b42b2c4
date added to LUP
2019-07-01 13:24:38
date last changed
2024-03-13 08:12:38
@article{fe62ad58-8c1d-4724-bfc2-557b6b42b2c4,
  abstract     = {{<p>The association between HLA-DQ haplotypes and insulin-dependent diabetes mellitus (IDDM) was studied in 48 children from 44 families ascertained from the high incidence area around Umea, Sweden. Numerous hypotheses have been proposed to explain associations between HLA and IDDM, but comparisons of statistical models based on these hypotheses have not been attempted. The aim of the present study was to compare the goodness-of-fit and predictive abilities among different statistical models. A likelihood-based analysis rather than a conventional analysis based on contingency tables was therefore adopted. We first used parental haplotype information in a conditional likelihood analysis (1) and then compared this analysis with that of an unaffected control group which used information on geographically matched controls. Under the analysis conditional on parental haplotype, a statistical model motivated by the hypothesis that the entire DQ heterodimer is involved in IDDM pathogenesis fit the data significantly better and had greater predictive ability than either a model motivated by the explanation that an IDDM gene is linked to DQB1 or that the DQB1 chain itself is involved in IDDM pathogenesis, or a model arising from the hypothesis that single amino acids at codon 57 of DQB1 and codon 52 of DQA1, respectively, confer susceptibility. Under the case-control analysis, the identity of the best-fitting or most predictive statistical model was not as clear, although both approaches to analyzing risk suggested that the single-amino-acids model had significantly poorer fit compared to the remaining two models.</p>}},
  author       = {{Graham, J. and Kockum, I. and Breslow, N. and Lernmark, Å and Holmberg, E.}},
  issn         = {{0001-2815}},
  keywords     = {{Diabetes mellitus, insulin-dependent; Disease susceptibility; Genetic marker; Haplotype; HLA-DQ antigen; Likelihood function; Model, statistical}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{1--14}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Tissue Antigens}},
  title        = {{A comparison of three statistical models for IDDM associations with HLA}},
  url          = {{http://dx.doi.org/10.1111/j.1399-0039.1996.tb02599.x}},
  doi          = {{10.1111/j.1399-0039.1996.tb02599.x}},
  volume       = {{48}},
  year         = {{1996}},
}