GenomicRisk AI

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72.0% riskHIGH

Patient Alpha

10 genes analyzed · 5 SNPs · 10 epistasis pairs

TCF7L2FTOSLC30A8PPARGKCNJ11CDKAL1IGF2BP2CDKN2A/BHHEXMTNR1B

SHAP Waterfall

feature attribution breakdown
TCF7L2
↑ TCF7L2 pushed risk +0.34
+0.340
FTO
↑ FTO pushed risk +0.22
+0.220
SLC30A8
↑ SLC30A8 pushed risk +0.18
+0.180
PPARG
↓ PPARG reduced risk -0.15
-0.150
KCNJ11
↑ KCNJ11 pushed risk +0.12
+0.120
MTNR1B
↑ MTNR1B pushed risk +0.11
+0.110
CDKAL1
↑ CDKAL1 pushed risk +0.09
+0.090
IGF2BP2
↑ IGF2BP2 pushed risk +0.07
+0.070
CDKN2A/B
↑ CDKN2A/B pushed risk +0.05
+0.050
HHEX
↓ HHEX reduced risk -0.04
-0.040
Final Score
72.0%

SHAP Beeswarm

Low feature value
High feature value
TCF7L2FTOSLC30A8PPARGKCNJ11CDKAL1IGF2BP2CDKN2A/BHHEXMTNR1BSHAP value (impact on model output)-0.50-0.250.000.250.50

Gene Biological Mapping

annotated by our research team
TCF7L2+0.340

Strongest T2DM risk locus — impairs insulin secretion via WNT pathway disruption

WNT signaling / beta-cell function
FTO+0.220

Obesity-linked locus — increases BMI through altered appetite regulation

Energy homeostasis / adipogenesis
SLC30A8+0.180

Zinc transporter in beta-cells — affects insulin crystallization and storage

Zinc transport / insulin granules
PPARG-0.150

Nuclear receptor — protective alleles improve insulin sensitivity in adipose tissue

Lipid metabolism / insulin sensitivity
KCNJ11+0.120

Potassium channel subunit — risk alleles cause beta-cell depolarization defects

ATP-sensitive K+ channel
CDKAL1+0.090

Modifies tRNA for proinsulin translation — affects insulin processing fidelity

tRNA modification / proinsulin processing
IGF2BP2+0.070

RNA-binding protein — risk variants reduce beta-cell mass maintenance

mRNA stability / beta-cell proliferation
CDKN2A/B+0.050

Cell cycle inhibitors — risk alleles accelerate beta-cell aging and apoptosis

Cell cycle regulation / senescence
HHEX-0.040

Homeobox transcription factor — essential for normal pancreatic organogenesis

Pancreas development

Epistasis Interaction Matrix

click a cell to see interaction details
TCF7L2
FTO
SLC30A8
PPARG
KCNJ11
CDKAL1
IGF2BP2
CDKN2A/B
TCF7L2
—
0.76
0.65
0.49
FTO
0.76
—
0.58
0.38
SLC30A8
0.65
—
0.52
PPARG
0.58
—
0.33
KCNJ11
0.49
0.52
0.33
—
CDKAL1
—
0.44
IGF2BP2
0.38
0.44
—
CDKN2A/B
—

Variant Suggestions

epistasis-aware allele recommendations
TCF7L2Pathogenic
-31% risk
CURRENT ALLELE

rs7903146_T

SAFER ALLELE

rs7903146_C

⚡ Combined with FTO rs9939609 A→T, interaction score drops 0.76 → 0.43

FTORisk factor
-18% risk
CURRENT ALLELE

rs9939609_A

SAFER ALLELE

rs9939609_T

⚡ Reduces adipogenesis-WNT crosstalk with TCF7L2

SLC30A8Protective
-14% risk
CURRENT ALLELE

rs13266634_C

SAFER ALLELE

rs13266634_T

⚡ T allele is actually protective — loss of function reduces T2DM risk

KCNJ11Risk factor
-9% risk
CURRENT ALLELE

rs5219_T

SAFER ALLELE

rs5219_C

⚡ C allele restores normal K-ATP channel gating in beta-cells

MTNR1BRisk factor
-8% risk
CURRENT ALLELE

rs10830963_G

SAFER ALLELE

rs10830963_C

⚡ C allele normalizes melatonin-mediated insulin timing