Transmission disequilibrium analysis of 31 type 1 diabetes susceptibility loci in Finnish families

Abstract

Currently more than 50 type 1 diabetes (T1D) loci outside the human leukocyte antigen (HLA)-region have been established in large European and/or North American populations. Our aim was to attempt to replicate these findings in the less heterogenic Finnish population and to explore evidence for genetic heterogeneity. We analyzed 1761 Finnish T1D trio families for association in 31 T1D loci (25 confirmed and 6 have inconsistent prior evidence). Families were categorized into nine different subgroups according to potential features that reflect underlying genetic heterogeneity in patients (age at diagnosis, sex and HLA genotypes). Seventeen confirmed loci and one nonconfirmed locus (1p31.1) presented significant evidence for association in the full data set. Magnitude and direction of effect was consistent with prior evidence. The strongest effects were seen at the insulin gene, PTPN22 and IL2RA regions. Tentative evidence of odds ratio (OR) heterogeneity within subgroups was seen in eight loci. Our findings were well in line with those reported in the latest meta-analyses using large admixed Caucasian populations, which concurs with the notion that the currently confirmed T1D loci, that have been discovered and replicated mostly in diverse populations, are common to all European populations. The observed effect modifications by subgrouping require validation in later studies with more statistical power.