Table 1.
Coding variants associated with genetic risk for T1D. For each coding SNP, chromosomal region, major and minor alleles, risk allele frequency, odds ratio (OR), amino acid (AA) substitution, prediction of functional effect and association with other autoimmune diseases are presented.
| Gene | Chromosomal region |
T1D associated coding SNP |
Major > minor alleles |
Risk allele |
Risk allele frequency |
T1D OR | Ref for OR |
AA substitution |
SIFT/ PolyPhen predictions |
Association with other autoimmune diseases |
||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| European | African | East Asian |
South Asian |
American | ||||||||||
| PTPN22 | 1p13.2 | rs2476601 | G > A | A | 0.094 | 0.003 | 0.000 | 0.013 | 0.036 | 1.81 | 6 | R620W | Tolerated/benign | RA, CD, JIA, V, MG, UC, CeD |
| CTLA4 | 2q33.2 | rs231775 | A > G | G | 0.359 | 0.388 | 0.637 | 0.310 | 0.463 | 1.20 | 6 | T17A | Tolerated/benign | RA, CD, UC, JIA |
| CD226 | 18q22.2 | rs763361 | C > T | T | 0.473 | 0.737 | 0.388 | 0.513 | 0.452 | 1.10 | 89 | G307S | Tolerated/benign | UC, CD, CeD, MS, RA |
| UBASH3A | 21q22.3 | rs13048049 | G > A | G | 0.949 | 0.973 | 1.000 | 0.990 | 0.981 | 1.19 | 6 | R324Q | Tolerated/possibly damaging | RA, UC, Ps, MS, CeD |
| SIRPG | 20p13 | rs6043409 | G > A | G | 0.660 | 0.825 | 0.848 | 0.858 | 0.782 | 1.14 | 5 | A263V | Tolerated/benign | RA, UC |
| TYK2 | 19p13.2 | rs34536443 | G > C | G | 0.971 | 0.999 | 1.000 | 0.994 | 0.980 | 1.54 | 6 | P1104A | Deleterious/probably damaging | Ps, RA, MS, CeD, UC, Sj |
| rs12720356 | A > C | A | 0.908 | 0.997 | 1.000 | 0.989 | 0.952 | 1.21 | 6 | I684S | Deleterious/possibly damaging | UC, CD, Ps, Sj, CeD, MS, AS, RA | ||
| SH2B3 | 12q24.12 | rs3184504 | C > T | T | 0.464 | 0.019 | 0.003 | 0.069 | 0.254 | 1.27 | 6 | R262W | Tolerated/benign | CeD, CD, Ps, UC, RA, JIA, MS, Sj |
| FUT2 | 19q13.33 | rs601338 | G > A | A | 0.441 | 0.491 | 0.004 | 0.283 | 0.341 | 1.12 | 6 | W154* | Loss of function | CD, MS, Ps |
| IFIH1 | 2q24.2 | rs1990760 | T > C | T | 0.605 | 0.126 | 0.187 | 0.564 | 0.390 | 1.14 | 6 | T946A | Tolerated/benign | UC, Ps, CD, MS, MG |
| rs35667974 | T > C | T | 0.990 | 0.999 | 1.000 | 0.999 | 1.000 | 1.64 | 6 | I923V | Tolerated/probably damaging | UC, Ps, CD | ||
| rs35337543 | C > G | C | 0.981 | 1.000 | 1.000 | 0.998 | 0.990 | 1.58 | 6 | Splice donor variant | Loss of function | UC, Ps | ||
| CTSH | 15q25.1 | rs2289702 | C > T | C | 0.895 | 0.985 | 0.929 | 0.847 | 0.947 | 1.26 | 6 | G11R | Deleterious/benign | - |
Minor allele reported in reference to + strand of DNA from European subjects and risk allele frequencies reported from 1000 Genomes Project phase 3 release V3+. T1D OR shown for risk allele from most recent GWAS including the variant. Predictions of impact on protein structure and function shown from SIFT (Sorting Intolerant From Tolerant) and PolyPhen-2 (Polymorphism Phenotyping v2). The “Association with other autoimmune diseases” column includes conditions in which the risk allele for T1D may carry risk or protection for the noted diseases. Disease associations reported from “Immune system” category of PheWAS from ImmunoBase version 0.4.0 (fcf5738). AS, ankylosing spondylitis; CD, Crohn’s disease; CeD, celiac disease; JIA, juvenile idiopathic arthritis; MG, myasthenia gravis; MS, multiple sclerosis; Ps, psoriasis; RA, rheumatoid arthritis; Sj, Sjogren’s syndrome; SNP: single nucleotide polymorphism; T1D: type 1 diabetes; UC, ulcerative colitis; V, vitiligo.