Type 1 Diabetes Genome Analysis Report

Sample: DEMO-SAMPLE | Generated: 2026-01-11 14:45:44 | Analysis Version: 1.0

Executive Summary

HLA-Based Risk
Very High
16.6× higher risk than general population
(Odds Ratio from published research)
HLA Markers
Risk: DR3-DQ2 / DR4-DQ8
Protective: None detected
Risk markers increase T1D likelihood; protective markers decrease it.
Non-HLA Variants
7 of 9

known T1D risk variants

More risk variants = higher genetic contribution
Technical Details (for researchers)
Non-HLA Genetic Risk Score (GRS)
  • Variants analyzed: 9
  • Carrying risk allele: 7
  • Non-HLA GRS: 2.704 (Above average)

GRS calculated per Sharp et al. 2019: sum of (dosage × ln(OR)) for each variant. PMID:30655379

Your HLA Type

DR3-DQ2
DR4-DQ8 (*04:01)

HLA Markers
Risk: DR3-DQ2 / DR4-DQ8
Protective: None

HLA-Based T1D Risk Assessment

Source: Erlich et al. (2008) Diabetes 57(4):1084-1092

Genotype

GeneAlleles
HLA-AA*02:01 / A*24:02
HLA-BB*08:01 / B*44:02
HLA-CC*07:01 / C*05:01
HLA-DQA1DQA1*05:01 / DQA1*03:01
HLA-DQB1DQB1*02:01 / DQB1*03:02
HLA-DRB1DRB1*03:01 / DRB1*04:01

Risk Assessment

Very High

Odds Ratio: 16.59

Source: Erlich 2008 (DR3/DR4 heterozygote genotype)

Interpretation: DR3/DR4 heterozygote - highest genetic risk for T1D

Risk Factors
  • DR3/DR4 Heterozygote: Yes
  • Has DR3: Yes
  • Has DR4: Yes (*04:01)
  • Has DQ2: Yes
  • Has DQ8: Yes
  • Protective Alleles: None

Identified Haplotypes

  • DR3-DQ2
  • DR4-DQ8 (*04:01)

Haplotypes pair your DRB1 + DQB1 alleles based on known linkage patterns. ATYPICAL = uncommon pairing, may lack published risk data.

Important Notes

  • This is the highest-risk HLA genotype for T1D
  • DR3/DR4 heterozygotes have ~16x increased risk compared to general population
  • Both DQ2 (DQB1*02:01) and DQ8 (DQB1*03:02) are present
How to read HLA codes

Example: DRB1*04:01

  • DRB1 = the gene name (on chromosome 6)
  • *04 = the allele group (this is "DR4")
  • :01 = the specific protein variant within DR4

Think of it like software versions: DR4 is the major version, :01/:02/:05 are minor variants that behave similarly.

DRB1 Alleles (DR types)
NameWhat it meansT1D Risk
DR3 Any DRB1*03:xx allele
e.g., *03:01		 High Risk
DR4 Any DRB1*04:xx allele
e.g., *04:01, *04:02, *04:05		 High Risk
DR13 Any DRB1*13:xx allele
e.g., *13:01, *13:02		 Neutral
DR15 Any DRB1*15:xx allele
e.g., *15:01		 Protective
DQB1 Alleles (DQ types)
NameWhat it meansT1D Risk
DQ2 DQB1*02:01
presents gluten & insulin peptides		 High Risk
DQ8 DQB1*03:02
presents insulin peptides to T cells		 High Risk
DQ6 Any DQB1*06:xx allele
e.g., *06:02, *06:04		 Protective
Why DR3/DR4 combination is highest risk

Having both DR3-DQ2 and DR4-DQ8 (one from each parent) creates ~16x risk - more than either alone. Why?

  • DQ2 and DQ8 each present different insulin peptides to immune cells
  • Together, they activate a broader range of autoreactive T cells
  • This "double attack" on beta cells is more destructive than either alone

Priority Variants

ChrPositionRefAltGenersIDEffectGenotypeDosageORGRSEffect AF (AMR)ClinVarPrioritySource
chr1114377568GAPTPN22rs2476601R620W0/111.96x+0.67010.0%benignHigh PriorityPMID:30655379
chr112182224TAINSrs689VNTR0/111.81x+0.59028.0%benignHigh PriorityPMID:30655379
chr106074707ATIL2RArs11594656Regulatory0/111.50x+0.41065.0%benignHigh PriorityPMID:30655379
chr2204738919GACTLA4rs30872433'UTR0/021.20x+0.36054.0%benignHigh PriorityPMID:30655379
chr12111884608TCSH2B3rs3184504W262R0/111.30x+0.26050.0%benignHigh PriorityPMID:30655379
chr1256482028TGERBB3rs2292239Intronic0/111.25x+0.22065.0%benignHigh PriorityPMID:30655379
chr1611179873AGCLEC16Ars12708716Intronic0/111.20x+0.18035.0%benignHigh PriorityPMID:30655379
Column Definitions & GRS Methodology (click to expand)
Column Definitions
  • Gene: Hover over gene name to see its function in T1D pathogenesis
  • Effect: Variant consequence - amino acid change (e.g., R620W = Arginine→Tryptophan at position 620) or genomic location (Intronic, 3'UTR, Regulatory, VNTR)
  • OR: Odds Ratio from GWAS. OR >1 = increased risk, OR <1 = protective
  • Genotype: Your genotype (0/0 = ref/ref, 0/1 = het, 1/1 = hom alt). 0/0* indicates inferred homozygous reference (position not in VCF variant calls)
  • Dosage: Number of risk alleles carried (0, 1, or 2)
  • GRS: Genetic Risk Score contribution for this variant
  • Effect AF (AMR): Effect allele frequency in Latino/Admixed American population from gnomAD v4.1 (via DRAGEN Nirvana). Note: gnomAD reports ALT allele frequency, so when the GWAS effect allele is the REF allele, we display (1 - ALT freq) to show the true frequency of the risk allele.
  • ClinVar: Clinical significance from ClinVar database (benign, pathogenic, uncertain significance)
GRS Calculation (Sharp et al. 2019)

The Genetic Risk Score is calculated using the validated T1D GRS2 methodology:

GRS contribution = Dosage × ln(OR)
  • Dosage: Number of risk alleles (0, 1, or 2)
  • ln(OR): Natural log of the odds ratio (β coefficient)
  • Total GRS: Sum of all individual GRS contributions

Reference: Sharp SA, et al. (2019) Diabetes Care 42:200-207. PMID:30655379

Known T1D GWAS Variants

ChrPositionRefAltGenersIDEffectGenotypeDosageORGRSEffect AF (AMR)ClinVarPrioritySource
chr1114377568GAPTPN22rs2476601R620W0/111.96x+0.67010.0%benignHigh PriorityPMID:30655379
chr112182224TAINSrs689VNTR0/111.81x+0.59028.0%benignHigh PriorityPMID:30655379
chr106074707ATIL2RArs11594656Regulatory0/111.50x+0.41065.0%benignHigh PriorityPMID:30655379
chr2204738919GACTLA4rs30872433'UTR0/021.20x+0.36054.0%benignHigh PriorityPMID:30655379
chr2163124051CTIFIH1rs1990760A946T0/001.20x0.00041.0%benignNo Risk AllelePMID:30655379
chr12111884608TCSH2B3rs3184504W262R0/111.30x+0.26050.0%benignHigh PriorityPMID:30655379
chr1910469975GCTYK2rs34536443P1104A0/001.30x0.0004.00%likely_benignNo Risk AllelePMID:30655379
chr1256482028TGERBB3rs2292239Intronic0/111.25x+0.22065.0%benignHigh PriorityPMID:30655379
chr1611179873AGCLEC16Ars12708716Intronic0/111.20x+0.18035.0%benignHigh PriorityPMID:30655379
Column Definitions & GRS Methodology (click to expand)
Column Definitions
  • Gene: Hover over gene name to see its function in T1D pathogenesis
  • Effect: Variant consequence - amino acid change (e.g., R620W = Arginine→Tryptophan at position 620) or genomic location (Intronic, 3'UTR, Regulatory, VNTR)
  • OR: Odds Ratio from GWAS. OR >1 = increased risk, OR <1 = protective
  • Genotype: Your genotype (0/0 = ref/ref, 0/1 = het, 1/1 = hom alt). 0/0* indicates inferred homozygous reference (position not in VCF variant calls)
  • Dosage: Number of risk alleles carried (0, 1, or 2)
  • GRS: Genetic Risk Score contribution for this variant
  • Effect AF (AMR): Effect allele frequency in Latino/Admixed American population from gnomAD v4.1 (via DRAGEN Nirvana). Note: gnomAD reports ALT allele frequency, so when the GWAS effect allele is the REF allele, we display (1 - ALT freq) to show the true frequency of the risk allele.
  • ClinVar: Clinical significance from ClinVar database (benign, pathogenic, uncertain significance)
GRS Calculation (Sharp et al. 2019)

The Genetic Risk Score is calculated using the validated T1D GRS2 methodology:

GRS contribution = Dosage × ln(OR)
  • Dosage: Number of risk alleles (0, 1, or 2)
  • ln(OR): Natural log of the odds ratio (β coefficient)
  • Total GRS: Sum of all individual GRS contributions

Reference: Sharp SA, et al. (2019) Diabetes Care 42:200-207. PMID:30655379

Data Sources & References

HLA Risk Assessment
  • Erlich H, et al. (2008) HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk: Analysis of the Type 1 Diabetes Genetics Consortium Families. Diabetes 57(4):1084-1092. PMID:18252895
GWAS Variants
  • Sharp SA, et al. (2019) Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident Diagnosis. Diabetes Care 42:200-207. PMID:30655379
  • Robertson CC, et al. (2021) Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes. Nature Genetics 53:962-971. PMID:34127860

Individual variant citations are linked in the "Source" column of the variant tables above.

Important Disclaimer

This report is for research and educational purposes only. It is not intended to provide medical advice, diagnosis, or treatment recommendations. Genetic risk assessment is complex and should be interpreted by qualified healthcare professionals in the context of clinical history and other factors.

The odds ratios and risk categories presented are based on population-level studies and may not accurately predict individual disease risk. Many individuals with high-risk HLA genotypes never develop Type 1 Diabetes, and some with low-risk genotypes do develop the disease.