Multiple DNA variant association analysis: application to the insulin gene region in type 1 diabetes

Julier, C., Lucassen, A., Villedieu, P., Delepine, M., Levy-Marchal, C., Danzé, P.M., Bianchi, F., Boitard, C., Froguel, P., Bell, J. and Lathrop, G. M. (1994) Multiple DNA variant association analysis: application to the insulin gene region in type 1 diabetes. The American Journal of Human Genetics, 55 (6), 1247-1254. (PMID:7977386)

Abstract

Association and linkage studies have shown that at least
one of the genetic factors involved in susceptibility to insulin-
dependent diabetes mellitus (IDDM) is contained
within a 4.1-kb region of the insulin gene. Sequence analysis
has led to the identification of 10 DNA variants in this
region that are associated with increased risk for IDDM.
These variants are in strong linkage disequilibrium with
each other, and previous studies have failed to distinguish
between the variant(s) that cause increased susceptibility
to IDDM and others that are associated with the disease
because of linkage disequilibrium. To address this problem,
we have undertaken a large population study of
French diabetics and controls and have analyzed genotype
patterns for several of the variant sites simultaneously.
This has led to the identification of a subset consisting of
four variants (-2733AC, -23HphI, -365VNTR, and
+1140AC), at least one of which appears to be directly
implicated in disease susceptibility. The multiple-DNAvariant
association-analysis approach that is applied here
to the problem of identifying potential susceptibility variants
in IDDM is likely to be important in studies of many
other multifactorial diseases.

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Contributors

Author: A. Lucassen

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