In Ghana, a pro-inflammatory haplotype of the TNF gene (higher TNF, lower IL10) was associated with earlier death in areas with low pathogen load but provided protection in high pathogen areas, particularly up to age 40.

“There is a fascinating study out of the Netherlands actually, now probably 10 years ago, looking at Ghana, which is an interesting country because there’s parts of the country that have sort of been cleaned up, they have fresh water, they have clean water from wells, and so pathogen deaths are low there. There’s other parts of the country where people are still drinking from polluted rivers. They did this fascinating study where they looked at this sort of haplotype in the TNF gene that is known to have an inflammatory. If you have one form of it, you have higher levels of inflammation. If you have the other, you have lower levels. As you predict, in parts of the country where you are protected so, you know, clean water, not going to die from infection, if you have the high TNF, low IL10, the sort of, the pro-inflammatory haplotype, in the parts of the country with low pathogen, you die sooner. But in high pathogen areas, you’re protected. And the protection all occurs in the early part of a lifespan, up to the age of 40, where across evolutionary time, that’s where you wanna survive, because that’s where you’re going to reproduce and live long enough to probably get your kids into survival age.