Sat. Oct 1st, 2022
Historical family trees provide useful new insights into the genetics of longevity, but represent a world of different health risks.
enlarge / Historical family trees provide useful new insights into the genetics of longevity, but represent a world of different health risks.

Romantic scenes that never happen: your eyes meet. Your heart flutters. This person is the one – you are sure, because you are convinced that they will live to be at least 95 years old. It’s what you’ve always dreamed of.

Longevity doesn’t usually appear on people’s lists of what they look for in a partner. But according to an article published this week in the magazine Genetics, longevity is strongly related to marital relationships, meaning that people are quite good at choosing partners who have similar longevity. By failing to explain that behavior, estimates of the genetic contribution to longevity have been greatly exaggerated.

I knew as soon as I saw your blood work

No one chooses partners based on how long they will live. As the authors of the article wisely point out, longevity “cannot be observed until death, after which the opportunity to mate has ended”. But as anyone who’s ever dated can tell you, there’s a good chance that people will marry their match (or close to it) with traits like wealth and education, which play an obvious role in longevity.

J. Graham Ruby, the lead author of the paper, works for Calico Life Sciences, a research and development company funded by Alphabet. Calico’s “mission is to use advanced technologies to advance our understanding of the biology that governs lifespan.” That’s why Ruby used huge amounts of data from Ancestry.com to investigate the role of genes in the lifespan of more than 400,000 people born in the 1800s and early 20th century.

When it comes to complex traits like longevity, huge numbers of genes will come into play, and so are countless environmental factors, so the role of genes is described in terms of how much variability it can account for. Estimates of genetic influence range from about 15 to 30 percent, meaning up to 30 percent of the variation you see in human lifespan can be explained by genetic differences between people.

Estimates vary partly because of differences in data sources and calculation methods and partly because the statistic will not be the same for different populations: countries differ in the most common causes of death, the environmental risk factors people face, and how many different people are exposed to the same risk factors. For example, in an impoverished country with a high risk of infectious diseases and death in childbirth, the few wealthy citizens can avoid these risks through expensive health care. That will look very different from a prosperous, egalitarian country where cancer is one of the leading causes of death.

Your lifespan is related to that of your brother-in-law

The calculations are complicated, but the rationale behind it is simple: if genes play a role in a trait, you should be quite similar to your siblings and parents, a little less like your cousins, less like your second cousins, and so on. On. Ruby and his colleagues used the family tree data to investigate whether lifespans were comparable between more closely and more closely related relatives. This yielded heritability estimates similar to those calculated previously: sibling longevity was highly correlated, cousins ​​slightly less correlated, and so on.

But the longevity of spouses was also correlated. That could easily be explained by spouses who share the same household and lifestyle: eating the same healthy diet or smoking cigarettes together. But the researchers noticed something strange: The longevity of other family members is only related to marriage also correlated. That cannot be explained by genes, and it cannot be explained by a shared environment.

So Ruby and his colleagues began researching in-laws longevity. They looked at sisters-in-law and in-laws, then at relationships such as “a sibling’s husband’s sibling” (your brother’s wife’s sister) and “a husband’s sibling’s husband” (the husband of your husband’s sister). Even in these distant relationships, life expectancies were correlated — if your partner’s sibling’s husband has reached old age, that means you’re a little bit more likely to do the same.

What’s going on here is assortative mating: people are likely to marry people who match them on certain traits, such as education and wealth, and those traits, in turn, are related to longevity. That high level of assortative mating greatly pushed up the heritability estimate. Once they took this into consideration, Ruby and his colleagues arrived at a much lower figure of seven percent genetic influence — at most. That seven percent includes both genetic and non-genetic traits, such as the healthy or unhealthy habits that parents pass on to their children. Those two things can be difficult to separate, but it’s reasonable to assume that the contribution of genetics is only lower.

It’s an estimate that could change, and likely has already happened, because this study was based on a historical dataset of people born in very different health landscapes and very different marriage practices. The Ancestry.com database is also overwhelmingly populated with details of American families with European heritages, limiting generalization to other groups, countries, cultures, and times. But it is an essential observation to think about heredity statistics in general, because assortative mating encompasses all kinds of characteristics. There’s also a negative assortative pairing, also known as ‘attracting opposites’, to play with.

This may seem like a disappointing result for a company interested in the ‘biology that determines longevity’. But the processes of aging and disease are of course still biological, even if the causes of those processes lie less in our genes than previously thought. In fact, examining what makes up the vast majority of differences in people’s longevity could yield exactly the most exciting answers.

Genetics2018. DOI: 10.1534/genetics.118.301613 (About DOIs).

By akfire1

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