How genetic study of lipid profile in Indian adolescents can Influence Heart Disease, Stroke
Although usually seen as an adult problem, genetic roots of dyslipidemia start in childhood. Studying lipid levels in Indian children is not only important for predicting future cardiac complications but can also provide critical insight into how genetic risks are inherited and further amplified by lifestyle factors common in India
Heart disease has been a long-standing health threat in India, striking people earlier and harder than in many other countries. But could the roots of this risk begin much earlier than adulthood — perhaps as early as childhood? Our genetic study published recently in the Journal of Human Genetics suggests exactly that: even before any symptoms appear, our genes may already be shaping the levels of fats in our blood, quietly laying the groundwork for future health problems.
Studying lipid profiles in children
India has one of the highest rates of heart disease in the world, and people here often develop it younger than elsewhere. A key reason is lipid levels in the blood, measured as good cholesterol (HDL), bad cholesterol (LDL), triglycerides, and total cholesterol. Abnormality in these lipid levels is known as dyslipidemia, which significantly increases the risk of heart disease and stroke. Although usually seen as an adult problem, what if the genetic roots of dyslipidemia start in childhood? So studying lipid levels in Indian children is not only important for predicting future cardiac complications but can also provide critical insight into how genetic risks are inherited and further amplified by lifestyle factors common in India, such as high-carbohydrate diets.
How genes come into play
Genes carry the instructions for how proteins are made and how different processes in the body are regulated. Within these genes, small variations, particularly the single nucleotide polymorphism (SNP), in the DNA sequence known as genetic variants, can alter how efficiently a gene functions. While such changes may seem minor, they can influence biological pathways, including those involved in lipid transport and metabolism. As a result, certain variants can predispose an individual to higher or lower levels of cholesterol and triglycerides, thereby modifying the risk of developing heart disease
To understand how genetic variation influences traits like lipid levels, researchers rely on large-scale approaches such as Genome-Wide Association Studies (GWAS) and Exome-Wide Association Studies (ExWAS). Genome-Wide Association Studies scan millions of common genetic variants across the entire genome to identify those statistically associated with a trait, with each variant typically exerting only a modest effect. In contrast, ExWAS focuses on the exome — the protein-coding portion of the genome that represents only about 1% of our DNA, where many rare variants reside that can directly alter protein structure or function and often have stronger effects on health.
We first carried out a large-scale GWAS involving more than 5,400 Indian adolescents ages 9-18 years to identify genetic variants associated with lipid profiles. To complement these findings, an ExWAS was next performed in 4,750 children, providing deeper insights into the genetic architecture of lipid regulation. While genome-wide association studies are well-suited for detecting common variants with modest effects, exome-wide association studies are particularly valuable for uncovering rare variants that can have stronger functional consequences. Together, these approaches offer an integrative framework for understanding the genetic basis of lipid metabolism. Our study is the largest single-cohort paediatric lipid study till date.
What our study found
We identified several important genetic contributors to lipid metabolism in Indian adolescents. The GWAS highlighted the role of well-established genes in influencing lipids — one gene (CETP) influencing HDL, two genes (CELSR2 and PSRC1) linked to LDL and total cholesterol, and three genes (GCKR, ZNF259, and TBL2) that affect triglyceride levels. The ExWAS, conducted in 4,750 children across more than 41,000 genetic markers, uncovered additional known loci, including one gene (ALDH1A2) for HDL, and five genes (APOE, APOC1, TM6SF2, CILP2, and TOMM40) for LDL and total cholesterol. For triglycerides, it identified two previously established genes (APOA5 and BUD13) as well as four novel genes (ATP8B3, MYH7B, GYS2, and RNF8). The identified significant associations showed consistent effect in the European population as well as in our 2019 study (Journal of Human Genetics) on Indian adults, suggesting that genetic risk factors for abnormal lipid levels are established early in life, independent of environmental influences. Some genes, like CETP, show effects that intensify with age, but their influence begins in childhood, underlining the potential of genetic screening to identify at-risk children well before clinical symptoms arise.
Functional analysis further showed that many of these genes are active in the liver and kidney — organs central to lipid processing — and are involved in pathways such as phospholipid and cholesterol transport and triglyceride metabolism. Importantly, several of these genes have also been linked to broader conditions, including coronary artery disease, myocardial infarction, Alzheimer’s disease, gout, and Type 2 diabetes, highlighting their wide-reaching impact on health.
Looking ahead
If genes can flag risks so early, then children at higher risk of high cholesterol could be identified before problems show up. The vital information opens the door to early interventions, such as changes in diet, physical activity, or even targeted medical care. Importantly, because India’s genetic makeup is different from the European population, relying only on European studies won’t give us the full picture. We need risk models that reflect Indian diversity.
Our latest research is a step toward personalised medicine, healthcare tailored to a person’s genetic makeup. By combining genetic screening with healthy lifestyle practices, it is possible to identify heart disease risks before they cause a crisis. Just as national programmes once successfully targeted malaria and kala-azar, a focused mission is now needed against childhood dyslipidemia and heart disease.
The message is clear — the seeds of heart health or heart risks are planted early. By paying attention to both our genes and our lifestyle early on, it is possible to change the course of heart disease in future generations in India.
