D2I2.
cardiovascular⚑ High burden in India

Coronary artery disease

disease (CAD), also called coronary heart disease (CHD), or heart disease (IHD), is a type of heart disease involving the reduction of blood flow to the muscle due to a build-up of atheromatous plaque in the of the heart. It is the most common of the diseases. CAD can cause stable , unstable angina, , and myocardial .

Underlined words are explained — tap any of them.

Symptoms — what it feels like

  • ·Chest pain, shortness of breath

Causes — why it happens

  • · of the of the heart

How it's found

  • ·, stress test, computed tomographic , coronary

Prevention

  • ·Healthy diet, regular exercise, maintaining a healthy weight, not smoking

Treatment

  • · intervention (PCI), coronary bypass (CABG)

Complications

  • ·Heart failure, abnormal heart rhythms, heart attack, ,
The genetics, in one picture

Who a European-built risk score flags as “high-risk”

The score (PGS000010) was tuned so 10% of Europeanscross the “high-risk” line (the dashed mark). Bars reaching past it are over-flagged; bars well short are under-flagged — either way the ruler is mis-set for that group.

Sri Lankan Tamil
1%
Punjabi (Lahore)
2%
South Asian (all)
2%
Telugu (India)
2%
Gujarati
2%
All-India · GenomeIndia
2%
Bengali
3%
European
10%

Share above the European top-10% cutoff. The All-India row is computed on GenomeIndia (≈10,000 genomes); the per-subpopulation rows on 1000 Genomes. Analytical mean-shift, not validated against Indian outcomes. See methods.

How common each gene variant is, by ancestry

The share of people carrying the effect version of each variant. South Asian is highlighted; where it differs from European, a risk model built on Europeans can misread it.

9p21/CDKN2B-AS1rs1333049Ensembl
African
21%
Admixed American
46%
East Asian
54%
European
47%
South Asian · 1000G (n≈489)
49%
All-India · GenomeIndia (n≈10,000)
50%
9p21/CDKN2B-AS1rs10757278Ensembl
African
16%
Admixed American
46%
East Asian
54%
European
47%
South Asian · 1000G (n≈489)
50%
All-India · GenomeIndia (n≈10,000)
51%
African
0%
Admixed American
3%
East Asian
1%
European
7%
South Asian · 1000G (n≈489)
1%
All-India · GenomeIndia (n≈10,000)
1%
African
0%
Admixed American
22%
East Asian
9%
European
1%
South Asian · 1000G (n≈489)
0%
All-India · GenomeIndia (n≈10,000)
1%

Effect-allele frequencies. All-India is the pooled large-sample number from GenomeIndia (≈10,000 Indian genomes); the South-Asian row is the smaller 1000 Genomes phase-3 panel, kept for finer per-subpopulation resolution.

Did you know?
A heart-disease gene score clears 99% of Sri Lankan Tamils - the group at higher true risk
The European coronary PRS flags just 0.7% of Sri Lankan Tamils (target 10%), under-warning a group with among the world's highest early heart-attack rates.
↓ Card
Source: D2I2 PRS analysis (1000 Genomes) / INTERHEART
Clopidogrel, a top heart-attack drug, misfires far more often in South Asians
The CYP2C19 loss-of-function allele that blunts clopidogrel sits at 36% in South Asians and 41% in Sri Lankan Tamils, versus 15% in Europeans.
↓ Card
Source: 1000 Genomes phase 3

The sections below are general education drawn from public guidelines (NHS, Mayo, CPIC, WHO, ICMR). They are not individually reviewed by a clinician and are not medical advice — always talk to a doctor about your own health.

When to see a doctor

See a doctor

See a doctor if you get chest tightness, pressure, or breathlessness when you walk, climb stairs, or feel stressed, and it eases with rest. Also get checked if you have several risk factors like diabetes, high blood pressure, high cholesterol, smoking, or a strong family history.

Get care urgently

Call emergency services now if you have chest pain or pressure spreading to the arm, jaw, neck, or back, with breathlessness, sweating, or nausea. This may be a heart attack. Do not drive yourself.

General guidance, not a diagnosis. When in doubt, see a doctor.

Questions to ask your doctor

  • ?Which tests will show how my heart and arteries are doing?
  • ?Given my family history and background, how high is my risk?
  • ?What lifestyle changes lower my risk the most?
  • ?What are my cholesterol, blood pressure, and blood-sugar targets?
  • ?What symptoms mean I should call for emergency help?
  • ?How often should I be reviewed?

What to note before your visit

  • ·when chest symptoms happen and what brings them on
  • ·family history of heart disease, especially at a young age
  • ·your blood pressure, cholesterol, and smoking history
  • ·current medicines you take
For clinicians · pharmacogenomics

Genes that change how certain drugs work — and that differ in South Asians. This is education, not a dosing tool; genotype-guided prescribing is a clinician decision.

CYP2C19Clopidogrel
CPIC A

is a 'switched-off' medicine that your body has to switch on using an called . Many South Asians carry a gene version that makes a weaker enzyme, so the drug never fully turns on and does less to stop dangerous - which is why a doctor may pick a different blood thinner instead.

South Asian signal: The loss-of-function alleles CYP2C19*2 (c.681G>A, rs4244285) and *3 (c.636G>A, rs4986893) are common in South Asians. In a British-South Asian clopidogrel cohort, ~13% were poor metabolisers (two LOF alleles) and ~57% carried at least one LOF allele (intermediate or poor) - higher than European (~2.4% PM) reference (JACC Advances 2023, PMC10550831). CYP2C19*2 allele frequency in South Asians is reported around 30-34% (Ionova et al., Clin Transl Sci 2020).

Prescriber note: In a South Asian ACS/PCI patient, a poor response to clopidogrel is more likely than European data suggest; where CYP2C19 genotype or a validated point-of-care test is available, an intermediate/poor metaboliser result supports switching to prasugrel or ticagrelor rather than escalating clopidogrel. For CYP2C19 intermediate or poor metabolisers with ACS/PCI, CPIC recommends avoiding clopidogrel and using an alternative antiplatelet (e.g. prasugrel or ticagrelor) where not contraindicated, because reduced clopidogrel activation raises the risk of major adverse cardiovascular events.

Not a dosing tool. Genotype-guided prescribing is a clinician decision; genotyping access in India is limited.

Test yourself

0/4 answered

4 quick questions on Coronary artery disease. Tap an answer to check it.

1. Coronary artery disease reduces blood flow to which muscle?
2. What builds up inside the arteries to cause coronary artery disease?
3. Which of these is a common symptom of coronary artery disease?
4. Which habit helps prevent coronary artery disease?
An open question — could you help answer it?

A European-trained for disease places only 0.7% of Sri Lankan Tamil people above its high-risk cut-off - far BELOW the 10% it was calibrated to. Yet South Asians carry a well-documented EXCESS of real-world heart disease. The score is blind to South-Asian coronary artery disease : it under-warns exactly the group at higher true risk. This under-flagging is more dangerous than over-flagging.

A study that would help: Build a South-Asian-specific disease score (or PGS000010) using Indian +outcome cohorts, then show it recovers the missing high-risk fraction that the European score drops. A clean, recalibration study.

Genomics deep dive · verified

The score that under-warns the very people most likely to have an early heart attack

The finding

For disease, the European score places only 0.7% of Sri Lankan Tamils above its high-risk line — far BELOW the 10% design target (our analysis). It under-flags. Yet South Asians have among the highest real-world coronary rates in the world, often a decade earlier than Europeans.

Why India specifically

The 'South Asian paradox' — high disease at relatively low and BMI — is long documented (INTERHEART and others). A score that quietly reassures exactly this group is the most dangerous failure mode: false comfort for those at highest true risk.

What's known — and the gap

The downward shift is measurable, and part of the biology is understood ((a), central adiposity, resistance). What's missing is a South-Asian score that recovers the high-risk fraction the European one drops.

A study you could fund

Build or a South-Asian score against Indian cohorts and show it recovers the missing high-risk group — turning a falsely-reassuring number into an actionable one.

Sources
  • Martin et al., Nature Genetics 2019 (PRS transferability)
  • Yusuf et al. (INTERHEART), Lancet 2004 — South Asian coronary risk
  • D2I2 PRS-transferability analysis (1000 Genomes phase 3)
Plain-language summary adapted from Wikipedia. Not medical advice.