Assessment of the Role of Common Genetic Variation in the Transient Neonatal Diabetes Mellitus (TNDM) Region in Type 2 Diabetes
A Comparative Genomic and Tagging Single Nucleotide Polymorphism Approach
Article Figures & Tables
Figures
- FIG. 1.
Schematic representation of the ZAC/PLAGL1 gene. Schematic representation of the ZAC/PLAGL1 gene region illustrating the nine exons of ZAC and the position of the 26 SNPs identified. tSNPs are indicated by arrows, and the 26 SNPs identified are shown as diamonds.
- FIG. 2.
Linkage disequilibrium (LD) pattern across the ZAC/PLAGL1 region. Schematic representation of the linkage disequilibrium across the ZAC gene region by measurements of D′ (A) and r2 (B) for 26 SNPs. SNPs with the highest level of linkage disequilibrium are shown in red, and those with the lowest level of linkage disequilibrium are shown in blue.
Tables
- TABLE 1
Clinical details of study subjects
Case subjects Control subjects Family study probands Unaffected siblings n 1,988 1,606 536 208 Male (%) 59 51 58 44 Age at diagnosis or testing (years)* 51 (45–57) 31 (28–35) 41 (36–47) 49 (43–55) BMI (kg/m2) 30.1 (26.7–34.2) 24.8 (22.2–27.8) 33.0 (28.9–37.4) 28.1 (25.4–31.2) Treatment D/O/I (%) 11/63/26 † 20/59/21 † Data are median (interquartile range) unless otherwise indicated. Only successfully genotyped subjects were included. No clinical details were available for the European Cell Culture Collection population control samples, so control characteristics are for the Exeter Family Study samples only.
- *
* Age at diagnosis for case subjects; age at study for control subjects.
- †
† Control subjects and unaffected siblings were not on treatment. D/O/I, diet/oral hypoglycemic agent/insulin.
- TABLE 2
Case and control subjects’ tSNP analysis
SNP name Alleles (1/2) Allele 1 frequency in control subjects OR (95% CI) for allele 1 P rs7761382 C/T 0.57 0.98 (0.89–1.08) 0.71 rs6570592 C/T 0.46 1.01 (0.92–1.11) 0.89 rs3818092 G/C 0.23 0.94 (0.84–1.05) 0.25 rs2076683 T/G 0.44 1.04 (0.95–1.15) 0.42 rs2257104 C/A 0.57 1.01 (0.92–1.11) 0.86 rs2076684 C/G 0.09 0.95 (0.80–1.14) 0.58 rs2064495 T/C 0.79 1.08 (0.96–1.21) 0.20 Exon8-8498C>T T/C 0.15 1.06 (0.93–1.21) 0.36 rs2268447 T/C 0.31 0.98 (0.89–1.08) 0.68 rs2247408 T/C 0.31 0.98 (0.89–1.09) 0.73 rs2328536 T/C 0.69 1.02 (0.92–1.13) 0.68 rs2273323 T/C 0.06 1.02 (0.84–1.25) 0.84 rs2092894 G/A 0.55 1.02 (0.93–1.12) 0.71 rs6937128 G/A 0.25 0.98 (0.88–1.10) 0.77 rs2064661 C/T 0.82 1.00 (0.88–1.13) 0.99 The case-control study had 80% power to detect an OR >1.2–1.4. The simple allelic OR model is presented. Multiplicative, recessive, and dominant models were all tested and were also negative.
- TABLE 3
Family-based tSNP analysis
SNP name Alleles (1/2) Overall observed allele 1 transmission Overall expected allele 1 transmission Overall P rs7761382 C/T 269 267 0.87 rs6570592 C/T 270 254 0.14 rs3818092 G/C 141 148 0.47 rs2076683 T/G 248 253 0.70 rs2257104 C/A 263 258 0.66 rs2076684 C/G 40 50 0.05 rs2064495 T/C 196 189 0.46 Exon8-8498C>T T/C 114 111 0.70 rs2268447 T/C 185 195 0.32 rs2247408 T/C 176 188 0.20 rs2328536 T/C 226 217 0.34 rs2273323 T/C 41 49 0.12 rs2092894 G/A 242 239 0.81 rs6937128 G/A 172 165 0.47 rs2064661 C/T 139 154 0.07 Results were analysed using the transmission-disequilibrium test/sib transmission-disequilibrium test methods. The family study had 80% power to detect ORs of 1.4 and 1.68 for MAFs of 50% and 10%, respectively.
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