The numbers on a routine blood test are strongly heritable, and one of them turned into a medicine: BCL11A was found because it moved fetal haemoglobin, and silencing it now treats sickle cell disease. The same data also warns that several of these numbers mark disease risk without causing it.
What this condition connects to
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
Prevalence
A 2016 genome-wide analysis tested 29.5 million variants against 36 blood cell traits in 173,480 European-ancestry participants (Astle et al., Cell 2016, PMID 27863252). A platelet meta-analysis in up to 66,867 people identified 68 loci (Gieger et al., Nature 2011, PMID 22139419). A red cell study in up to 135,367 people identified 75 loci explaining 4-9% of the variance per trait (van der Harst et al., Nature 2012, PMID 23222517).
Inheritance
Common variants, each shifting a count or an index slightly, on a strongly heritable but highly polygenic set of traits. Distinct from the inherited blood disorders — sickle cell disease and the thalassaemias — which are caused by specific changes in the globin genes and are tested for directly.
A full blood count is the most ordered test in medicine. It reports how many red cells, white cells and platelets are in a sample, and how big they are. Most people have seen one. Almost nobody has been told that those numbers are among the most heritable things a laboratory measures.
How much of this is genetic
A 2016 study tested 29.5 million genetic variants against 36 red cell, white cell and platelet properties in 173,480 people. A 2011 meta-analysis in up to 66,867 people found 68 loci for platelet count and volume alone. A 2012 study of up to 135,367 people found 75 loci for red cell traits.
And here is the honest size of it: those 75 loci together explain 4-9% of the variation per trait. Heritable is not the same as explained, and a blood test gives you the actual number in an afternoon.
One of these numbers became a medicine
This is the part worth reading even if you never look at the list below.
Some adults keep making a little fetal haemoglobin — the form of haemoglobin a baby uses before birth — instead of switching entirely to the adult form. How much varies between people, and it is inherited. On its own that is a curiosity: a number on a blood test.
In 2008 genetic association studies traced that variation to a gene called BCL11A, and noticed something else at the same time. People with sickle cell disease and beta-thalassaemia who happened to keep more fetal haemoglobin had milder illness. The same paper that tied BCL11A and the HBS1L-MYB region to fetal haemoglobin levels also tied them to how often people with sickle cell disease had pain crises.
Later that year BCL11A turned out to be the switch itself: the repressor that shuts fetal haemoglobin off during development. In 2013 the common variation found by those association studies was localised to a noncoding enhancer of BCL11A that works only in red cell precursors — which is exactly the piece you would want to disable, because switching the gene off everywhere would do other damage.
Silencing BCL11A in a person's own blood stem cells raises fetal haemoglobin, and fetal haemoglobin does not sickle. That is now a treatment for sickle cell disease.
This site holds rs11886868 in BCL11A and rs7775698 in HBS1L. They are on this page because they move a blood index. What they led to is the best answer this catalogue has to the question of why anyone would study a routine laboratory number.
Clinical detail
And the same study says be careful with the rest
Blood cell numbers have been linked to plenty of diseases in ordinary observation — high white cell counts with heart disease, platelet measures with strokes. The 2016 study asked whether those links are causal, using the same natural-experiment logic that undid the HDL hypothesis on the cholesterol page.
It found both answers in one sentence. There are shared genetic pathways between blood cell indices and autoimmune diseases, schizophrenia and coronary heart disease. And there is evidence that previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.
So: real biology connecting these counts to serious illness, and at least some of the headline associations being a reflection of something else rather than a cause of it. Both are true, and the second is the one that gets left out.
What the variants on this page do
They shift a number slightly. Some of the genes are recognisable to anyone who has read about blood — GATA2 and GFI1B are transcription factors that direct how blood cells are made, HK1 is the first enzyme of glycolysis and red cells run entirely on it, TRIM58 acts late in red cell maturation. Most of the rest are regulatory regions with no familiar name.
What this page cannot do
It cannot tell you your blood counts. A full blood count does, costs very little, and is the test any doctor would order first.
It cannot explain an abnormal result. A count outside the reference range has causes a common-variant catalogue does not see — bleeding, infection, iron, B12, medicines, marrow disease. An abnormal result is a reason to see a doctor, not a reason to read a genotype.
It cannot tell you whether you carry sickle cell disease or thalassaemia. Those are caused by specific changes in the globin genes and are tested for directly. The fetal haemoglobin variants here modify how severe such a disease is in someone who already has it; they do not cause or exclude it.
Related variants MyGeneLog checks for
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Blood Cell Counts comes down to these specific, well-studied positions — not a diagnosis. 147 positions are linked to this page; the ones this page's own text discusses are shown first.
The New England journal of medicine · 2021 · PMID 33283990
Frequently asked questions
Can a DNA test tell me my blood counts?
No. A full blood count measures them directly, costs very little, and captures everything genetics cannot see — bleeding, infection, iron, vitamin B12, medicines and marrow disease. The variants here shift averages by small amounts.
My platelet count came back low. Does a variant here explain it?
Almost certainly not on its own. A count outside the reference range needs a doctor, because the causes that matter are mostly ones a common-variant catalogue does not carry. These variants shift a normal number a little; they do not produce an abnormal one.
How did a blood test number turn into a treatment?
Genetic studies found that variation near BCL11A changed how much fetal haemoglobin adults keep. BCL11A then turned out to be the switch that shuts fetal haemoglobin off, and the associated variation was localised to an enhancer that works only in red cell precursors. Silencing it raises fetal haemoglobin, which does not sickle, and that is now a treatment for sickle cell disease.
Do these variants tell me whether I have sickle cell disease?
No. Sickle cell disease and thalassaemia are caused by specific changes in the globin genes and are tested for directly. The fetal haemoglobin variants on this page modify how severe such a disease is in someone who already has it.
Blood counts are linked to heart disease. Is that a real cause?
Partly, and the honest answer is that some of it is not. The 2016 study found shared genetic pathways with autoimmune disease, schizophrenia and coronary heart disease, and in the same analysis found evidence that previously reported associations between blood cell indices and cardiovascular disease may be non-causal.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.