rs12740374
SORT1, the LDL variant whose mechanism was actually solved
What this position does
Most common variants are found by statistics and their mechanism stays unknown. This one was chased all the way down: it creates a binding site for a liver transcription factor, changing how much SORT1 the liver makes, which changes how much LDL cholesterol the liver clears.
Liver and cholesterol. Shaped by clearing cholesterol from blood. This is one of the variants that differs sharply between human populations, because something in the environment made one version worth having.
Salt, fat and blood pressure
Holding on to salt and water was the right instinct for almost all of human history. So was storing fat. Neither is an advantage in a shop.
What changed: Industry, roughly the last two centuries. Indoor work, heated buildings, refined food, cheap salt and sugar, tobacco at scale, and a collapse in infectious disease. This is where most of the deals in your genome came undone.
Why it spread: nobody knows. The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing.
Spiral Staircase, chapter 8: The Heart That Remembers the Savanna Spiral Staircase is written by the same author as this site.
What each result means
| If you carry | What it means |
|---|---|
| No copies of the effect version GG | You have the higher-LDL version on both copies Associated with higher LDL cholesterol on average. |
| One copy GT | You carry one lower-LDL copy Associated with modestly lower LDL cholesterol and a correspondingly lower heart disease risk. |
| Two copies TT | You have the lower-LDL version on both copies Associated with the lowest average LDL at this position, around 8 mg/dL lower, and roughly 40 per cent lower risk of heart attack in the original study. Your actual LDL is measured by a cheap blood test, which is what counts. |
How common each version is
| Ancestry group | T (the effect version) | |
|---|---|---|
| African | 24.7% | |
| American | 20.5% | |
| East Asian | 4.3% | |
| European | 21.3% | |
| South Asian | 25.9% |
1000 Genomes Project phase 3, via Ensembl, retrieved 2026-09-23. These groupings are coarse and flatten a great deal of internal diversity, particularly within Africa. A variant being common somewhere tells you where a piece of your ancestry probably comes from, and nothing else.
How many people carry each result
| Ancestry group | GG | GT | TT |
|---|---|---|---|
| African | 361 / 661 | 273 / 661 | 27 / 661 |
| European | 317 / 503 | 158 / 503 | 28 / 503 |
| East Asian | 462 / 504 | 41 / 504 | 1 / 504 |
| South Asian | 279 / 489 | 167 / 489 | 43 / 489 |
| American | 222 / 347 | 108 / 347 | 17 / 347 |
Counts of people, not modelled frequencies: every one of the 2,504 individuals sequenced by the 1000 Genomes Project phase 3, tallied by the genotype they carry. Deriving these from allele frequencies instead would assume random mating inside each group and undercount the homozygotes.
How to find out which you have
If you have taken a test with 23andMe, AncestryDNA, MyHeritage, Family Tree DNA, TellMeGen or Living DNA, this position is very likely already in the raw data file they gave you. You do not need another test.
One thing to watch if you look it up by hand: testing companies report some positions from one DNA strand and some from the other, and the file does not say which. Read the letters as they appear and you will get the opposite of the truth for some positions. Sequencings resolves that automatically.
Source
Coordinates and allele pair verified against Ensembl GRCh37. Direction of effect verified against VEP protein consequences or 1000 Genomes population frequency. Category: Population adaptation.
Where this fits
Common questions
What is rs12740374?
rs12740374 is a position in the SORT1 gene on chromosome 1. Most common variants are found by statistics and their mechanism stays unknown. This one was chased all the way down: it creates a binding site for a liver transcription factor, changing how much SORT1 the liver makes, which changes how much LDL cholesterol the liver clears.
What does it mean if I have TT at rs12740374?
You have the lower-LDL version on both copies. Associated with the lowest average LDL at this position, around 8 mg/dL lower, and roughly 40 per cent lower risk of heart attack in the original study. Your actual LDL is measured by a cheap blood test, which is what counts.
What does it mean if I have GG at rs12740374?
You have the higher-LDL version on both copies. Associated with higher LDL cholesterol on average.
How do I find out my rs12740374 genotype?
If you have taken a home DNA test, this position is very likely in the raw data file you were given. Sequencings reads that file in your browser without uploading it, and resolves which DNA strand each position was reported from, which is the step most manual lookups get wrong.
This is reference information, not medical advice, and not a diagnosis. See the medical disclaimer. Category: Population adaptation.