Total cholesterol

Total cholesterol combines LDL, HDL and other lipids in the blood. This score estimates your genetic tendency toward higher or lower total cholesterol.

What this total cholesterol score reads

This is PGS003830, developed by Zhang and colleagues in a 2023 Nature Genetics paper on multi-ancestry polygenic prediction. Unusually for this catalog, it was built and validated in South Asian samples: GWAS data from 34,135 South Asian individuals, development in 5,147, and evaluation in 5,153.

It uses clumping and thresholding, a simple method that keeps independently associated variants above a significance cut-off, and arrives at 32 variants. That is a small score for a trait this polygenic.

How well it predicts total cholesterol

In the paper's South Asian validation sample it explained 1.8% of the variation in total cholesterol. That is the honest headline: this score carries a little information about your inherited leaning and almost none about your actual number.

For comparison, the LDL score on this site explains around 9% of LDL variation in the population it was built for. Total cholesterol is a composite of LDL, HDL and other lipid fractions that move in different directions, which is part of why a single score for it predicts poorly.

How to read a high or low score

Treat this one lightly. At under 2% of variation explained, a high or low percentile should not change anything you do, and it is not a reason for reassurance or concern on its own.

Total cholesterol is also the least useful of the standard lipid numbers clinically. LDL cholesterol, and increasingly non-HDL cholesterol, are what guide treatment, because a high total can come from high LDL or from high HDL and those mean different things.

What this score does not capture

Single-gene causes of high cholesterol, familial hypercholesterolemia above all, are invisible to it, as are diet, body weight, thyroid disease and medication effects. A standard lipid panel measures the real values, breaks them into fractions, and costs very little.

Ancestry and accuracy

This score is one of the rare ones built specifically outside European-ancestry data, which is a genuine strength for South Asian users and a caution for everyone else: a score developed and validated in South Asian samples has not been shown to carry the same information in other populations.

How much of this score your file covers

31 of the published score's 32 variants are present in a standard consumer DNA file (97%). The remaining one cannot be read from one, so a result computed here approximates the published score rather than reproducing it.

Common questions

Should I use total cholesterol or LDL? LDL, or non-HDL cholesterol, for anything decision-related. Total cholesterol lumps together fractions that carry opposite associations with heart disease, which is why guidelines have moved away from it as a treatment target.

Why is this score so weak? It uses 32 variants, drawn from a GWAS of about 34,000 people. Scores built on millions of participants capture far more, and even those explain a minority of variation. The number reported here, 1.8%, is what the authors measured rather than an estimate.

Related

Beta-carotene to vitamin A conversion (BCO1) · Fat taste sensitivity (CD36) · Folate metabolism (MTHFR gene) · HDL cholesterol · LDL cholesterol · Triglycerides · Vitamin D status (low-D genetic burden)