Cholesterol genes are not universal

Using the Uganda Genome Resource - an unprecedented data set of thousands of people's DNA - researchers investigated the genes behind blood fats like cholesterol. Blood fat levels are one of the big risk factors for cardiovascular disease. And in Europeans and Asians, the genes involved are already known. But it seems that many of those genes don't work the same when it comes to Ugandans. Phil Sansom spoke to lead author Karoline Kuchenbaecker, who did this work while at the Sanger Institute...

Karoline - A lot of the studies we've done only included people of European descent and that's quite important because now we know about thousands and thousands of parts of the genome that link to diseases. Imagine that's all just applicable to white people, that would be a major problem for a country like the UK. So, what we did is we studied cholesterol in different groups, so we had data from China, Japan, from the UK, Europe, and also from Uganda. What we found was actually quite surprising. There was a group of genes that affect cholesterol in white people but doesn't do so in the Ugandans.

Phil - How is that possible?

Karoline - One hypothesis to explain this difference in this case is that some of the genes make you eat more unhealthy foods that contain a lot of cholesterol. Now, take the same gene in rural Uganda. You can't just drop into McDonald's, it's impossible. The gene wouldn't affect your cholesterol because it can't make you eat more unhealthy food. That's a very simple example. The biology behind some of the other genes might be more complicated or more biological in the sense that even if you eat unhealthily, it affects how your body metabolizes, but my guess is that it's really all about diet.

Phil - And is cholesterol something that we already knew a lot of the genes that were, I guess, we thought were responsible for it?

Karoline - Yes, definitely. So cholesterol has been very well studied because it's so important. Cholesterol is one of the major risk factors for cardiovascular disease. The genetic aspect of it is becoming more and more clinically relevant. We're beginning to use in clinics to screen people to understand the diseases, to identify people at risk, but based on what we found, it would only be applicable for people from European background.

Phil - Yeah, it seems like a pretty big deal, right?

Karoline - Yeah. I mean part of the reason is just that we didn't have data for anyone else for such a long time. And then there was the general assumption that everything would be universal. So yeah, it's a major problem that we have to address.

Phil - Why have most studies been done for only white people?

Karoline - In the early days of genetics, we wanted to make sure that the findings were actually correct and if you look at a group that's more similar to each other, that's actually easier. You feel more confident, but then this has become a sort of thing that everybody does. I think there's also a bit of a racial bias in terms of most researchers in the countries where this research is done are white. It wasn't, yeah, it wasn't recognized as a problem for a long time.

Phil - Now, what groups do you actually mean when you say that? Cause I know there's no such thing as like a genetic race of white people versus a genetic race of black people. That's all debunk science.

Karoline - You're completely right. Genetics operate on a continuum. When I say groups, I'm a bit artificially putting people together. What has happened is that between these so-called groups, there are some small genetic differences and that happened in our population history. There's a lot of mixing. It's a continuous thing, but most of the time the people who have been studied are the ones who have predominantly European ancestry and they are also of course different to some extent, but there are very few people with more African ancestry that have been included in these studies and even across Europe. The three countries that have been studied really extensively is the US the UK and Iceland.

Phil - But you keep saying ancestry, it sounds like that's the key thing, right?

Karoline - Absolutely. We are really defining the space on genetics.

Phil - You did just say that you thought that some of the gene variants for cholesterol were different for Ugandan people based on the environment they lived in. Isn't in this case, the environment the more important thing rather than where you come from?

Karoline - Yes, it could be, but it tells us that when we studied genetics, in a way a lot of geneticists think this is an easy thing to do because genetics is sort of very clear, right? You carry a gene variant or you don't and it doesn't change. The takeaway message from this is that genetics are happening in environments. There's so much variation, and of course genetics are so complex that it would be a silly assumption to think that they're just working the same way everywhere.

Phil - What are the implications, also, if you, maybe you live in the U K and you go to see your doctor about your cholesterol, but you're from Uganda, or you've got a parent from Uganda or grandparent or something like that? Is this information then going to make a difference?

Karoline - Yes. So if you have a grandparent from Uganda and you go to the hospital and you want to know about your genetic risk for high cholesterol, we can't help you in a way.