Table 1

Type 1 diabetes risk stratification by family history and genetic susceptibility

PopulationRisk of type 1 diabetes (%)Frequency in population (%)Frequency in all type 1 diabetes (%)
Low risk (<1%)
 Newborns: European/U.S. population0.4–1100100
 Newborns with HLA protective genotypes (124)<0.05757.2
 FDR with HLA protective genotypes (124)0.30.3<1
 FDR with low gene risk score* (HLA and non-HLA risk genes) (23)<10.1<1
Intermediate risk (1–12%)
 Newborns with HLA high-risk genotypes (37)44–536
 Newborns with high gene risk score** (HLA and non-HLA risk genes) (23)12127
 Newborn first-degree relatives of people with type 1 diabetes50.5–110
High risk (12–25%)
 FDR plus HLA high-risk genotypes (125)10–200.1<5
 FDR plus high gene risk score*** (HLA and non-HLA risk genes) (23)400.1<5
 Multiple affected FDRs (126)20–25<<0.1<<5
Very high risk (>25%)
 Identical twin of a patient with type 1 diabetes (28,29)30–70<<0.1<<5
 Multiple affected FDRs plus HLA risk genotypes (126)50<<0.1<<5
 Sibling affected plus HLA risk genes, identical by descent (30)30–70<<0.1<<5
  • FDR, newborn first-degree relatives of people with type 1 diabetes. HLA risk genotypes: HLA DRB1*03 and *04 and DQB1*0302. HLA protective genotypes: HLA DQB1*0602, *0301, *0303, *0603, and *0503. Genetic risk score derived from HLA plus nine single nucleotide polymorphisms from PTPN22, INS, IL2RA, ERBB3, ORMDL3, BACH2, IL27, GLIS3, and RNLS genes. *Threshold set to lower 10th centile of FDR; **threshold set to upper 99th centile of general population; ***threshold set to upper 90th centile of FDR.