The Genome Doesn't
Speak One Language

In a case-control study, ~all (44/44) Han Chinese SJS/TEN patients carried HLA-B*15:02. Carriage was ~3% in tolerant patients and ~8.6% in healthy controls. Odds ratio for SJS/TEN >2,500.

Taiwan mandated genetic testing before carbamazepine. Anukriti can stratify Asian vs non-Asian cohorts and surface population-specific risk early.

HLA-B*15:02 frequency: ~11.6% Singapore, 8.4% Malays, 6.1% Thais, 5.3% Filipinos. Carbamazepine is among the most common SJS/TEN causes regionally.

Population-wide screening introduced. Anukriti can simulate high-risk vs low-risk genotype distributions when modelling alternative therapies.

Reports of carbamazepine-induced SJS/TEN, especially in Tamil and Telugu ancestry. HLA-B*15:02 frequency varies across Indian groups; pre-therapy testing is now recommended.

Anukriti supports multi-ethnic Indian cohort exploration to evaluate the impact of genotype screening.

HLA-B*15:02 is virtually absent (~0%) in European and African-descent populations. Routine screening is not required.

Low frequency explains why early Western clinical trials missed the risk — exactly the bias Anukriti is designed to expose.

Hypersensitivity occurred in 5–8% of White patients pre-screening. HLA-B*57:01 frequency ~6.8% in Europeans. Routine genotyping reduced incidence to <0.5%.

Demonstrates how a single allele test transforms safety. Anukriti can simulate the "screen vs no screen" delta on synthetic cohorts.

Allele frequency reaches ~11% in Southwest Asian groups; ~3–5% in some Indian studies. Pre-prescription screening recommended.

Anukriti can model Indian and Southwest Asian cohorts to plan region-specific protocols.

Allele frequency ~1% in African populations; observed hypersensitivity ~2–3%. Routine screening still advised.

Illustrates how allele-frequency differences shift risk. Useful for global protocol planning.

Frequencies range 2–3% (Mexicans 2.2%, South Americans 2.6%). Many countries implement screening.

Even moderate-frequency populations benefit from genotyping; Anukriti can quantify cohort-level outcomes.

Caucasians required highest mean dose (~4.4 mg/day); Asians lowest (~2.5 mg/day); Native Hawaiians and Portuguese intermediate (~3.8 mg/day). Differences traced to CYP2C9 and VKORC1 variants.

Anukriti can model dose distribution by ancestry and quantify risk of mis-dosing.

High frequency of VKORC1 −1639 A allele drives lower maintenance doses (~2–3 mg/day) than in Caucasians.

Stratified dosing protocols; Anukriti can simulate regional cohorts to plan trial dosing.

Higher CYP2C9*2/*3 prevalence; typical doses 4–6 mg/day. Without genotyping, dose adjusted empirically.

Anukriti synthesizes how genotype-aware vs empiric dosing changes adverse outcome rates.

~2% of Caucasians and ~4% of African Americans are CYP2C19 poor metabolizers. ~20% are intermediate metabolizers. FDA labels carry boxed warnings for poor metabolizers.

Even Western populations show meaningful variability. Anukriti can model the benefit of switching to prasugrel or ticagrelor.

Loss-of-function alleles much more prevalent: ~14% PM in Chinese, up to ~57% in Pacific Islanders. Intermediate metabolizers >45% in East Asians.

Region-wide alternative therapy may be justified. Anukriti can simulate East Asian and Oceanian cohorts to quantify failure risk.

Intermediate metabolizer frequency >40%. Many patients potentially benefit from genotype-guided therapy.

South Asian cohort modelling helps plan pre-therapy genotyping policies.

Highest poor-metabolizer frequency (~57%). Clopidogrel may be ineffective in over half the population.

Strongest case for population-wide alternative agents; Anukriti makes the magnitude visible.

Up to ~28% are CYP2D6 ultra-rapid metabolizers. Rapid morphine production raises risk of life-threatening respiratory depression at standard doses.

FDA contraindications followed pediatric tonsillectomy reports. Anukriti can quantify risk in synthetic high-UM cohorts.

Duplicated CYP2D6 alleles in ~10% of Caucasians, ~3% in African Americans. PM alleles (*4, *5, *6) more common in Europeans; *17 more common in Africans.

Moderate but meaningful risk; especially relevant in pediatric and breastfeeding contexts.

Only ~1% UMs in Chinese/Japanese populations, but >50% of CYP2D6 alleles show reduced function or duplications.

Highly variable analgesic efficacy; Anukriti models analgesic response distribution by region.

UM frequencies 1–10%; PM phenotypes 5–10%. Caution advised in pediatric and postpartum populations.

Highlights global heterogeneity; cohort-level modelling helps protocol planning.

G6PD deficiency affects ~400 million people globally. Prevalence ~5% globally; >25% in malaria-endemic regions. ~12% of African Americans in the US are G6PD deficient.

Anukriti models hemolytic-event frequency under different dosing strategies and the value of screening.

Prevalence often >25%. G6PD A− is common and produces mild-to-moderate hemolysis. WHO recommends weekly dosing for deficient individuals.

Anukriti can simulate African cohorts and evaluate alternative regimens like tafenoquine or weekly primaquine.

G6PD Mediterranean variant causes severe hemolysis. Frequencies: 0.5% Portuguese males, 6.4% Cypriots, 8.3% newborn Greek males.

Demonstrates that "European" is not homogeneous; Anukriti supports safer dosing protocols.

Wide variation: 9–31% Thailand, ~30% Kachin (Myanmar/China border), 8% Laos, 9% Vietnam, 15.8% Myanmar. Variants include G6PD Canton and Viangchan.

Anukriti enables Southeast Asian cohort modelling to evaluate weekly dosing and alternative regimens.

Lower prevalence (2–3%) but present in specific ethnic groups. Screening still recommended.

Mixed-ancestry simulation is critical in Latin American populations.

~21.6% developed antituberculosis drug-induced hepatotoxicity (ATDH). Slow acetylators: 16.7% ATDH vs 4.9% in rapid/intermediate. Onset earlier in slow acetylators (median 0.5 vs 2 months). Adjusted hazard ratio ~3.05.

Anukriti can model liver injury risk and explore dose adjustments by NAT2 status.

Slow acetylator (SA) prevalence: ~60.16% Africa, ~58.93% Europe, ~41.94% Americas, ~34.42% Asia. DILI in SA carriers: 41.86% Africa, 42.83% Asia, 27.36% Europe, 29.06% Americas. Rapid acetylators (RA) more common in Asia (28.54%) than Europe (6.24%).

Anukriti models global NAT2 phenotype variation to guide genotype-aware dosing strategy.

Rapid acetylators more prevalent (some studies >40%). Standard dosing may underexpose patients, leading to treatment failure.

Anukriti can explore RA-dominant cohorts to test higher-dose protocols.

Key variants: c.1905+1G>A, c.2846A>T, c.1236G>A, c.1679T>G. DPYD*2A frequency: ~0.024 Finnish, 0.006 non-Finnish Europeans. Heterozygotes can develop life-threatening toxicity at standard doses.

Pre-treatment DPYD genotyping adopted in several European countries; Anukriti models prevention impact.

DPYD*2A: ~0.004 South Asian, 0.003 Middle Eastern. c.85T>C frequency: 0.072 East Asians, 0.255 South Asians. c.577A>G in 2.2% of Africans. Novel Indian/Japanese variants cause severe toxicity.

European panels miss variants relevant to non-European populations. Anukriti can evaluate universal vs region-specific genotyping.

Several Caucasian DPYD variants (c.1905+1G>A, c.1679T>G, c.1601G>A) absent in East Africans and Japanese. East Asians carry novel variants of unknown significance.

Highlights diversity of DPYD variation and need for region-specific risk allele research.

Carriers of rs1801160 A allele had 1.73× higher overall toxicity and 2.37× higher hematological toxicity vs GG. Allele frequency: 0.046 Europeans, 0.098 South Asians.

Even moderate-frequency variants meaningfully shift toxicity. Anukriti can quantify cohort-level adverse-event reduction.