Tuesday , June 22 2021

Genetics plays fewer roles in the lifespan than we thought

Historic family trees bring useful new insights into longevity genetics, but represent the world with different health risks.
Enlarge / Historic family trees bring useful new insights into longevity genetics, but represent the world with different health risks.

A romantic scene that never happened: your eyes met. Your heart is pounding. This person is the person – you are sure of that, because you believe they will live at least 95 years old. That's what you always dreamed of.

Age usually does not appear on people's lists of what they are looking for at partners. But, according to a paper published this week in the journal Geneticslongevity is strongly correlated with marital relationships, which means that people are quite good at choosing partners who live the same life span. Failing to take into account that behavior means that estimates of genetic contributions to longevity have been substantially overinflated.

I know the second I see your blood

No one chooses partners based on how long they will live. As written by paper writers, age "cannot be observed to death, at that time the opportunity to mate has ended." But because anyone who has dated can tell you, people tend to marry their partners (or close to them) in characteristics such as wealth and education, which play a clear role in longevity.

J. Graham Ruby, lead author on paper, works for Calico Life Sciences, a research and development company funded by Alphabet. "Calico's mission is to utilize advanced technology to enhance our understanding of biology that controls age." So Ruby uses a large amount of data from Ancestry.com to investigate the role of genes in the life span of more than 400,000 people born in the 1800s and early 20th century.

When it comes to complex features such as age, a large number of genes will play a role, and so many environmental factors, so the role of genes is explained in terms of how much variability can be explained. Estimates of genetic influences have ranged from 15 to 30 percent, which means that up to 30 percent of the variation you see in the human life span can be explained by genetic differences among people.

Estimates vary partly due to differences in data sources and calculation methods and partly because statistics will not be the same across different populations: different countries in the most common causes of death, environmental risk factors faced by people, and how many different people are exposed to the same risk factors . For example, in poor countries with a high risk of infectious diseases and deaths during childbirth, some wealthy citizens can avoid this risk through expensive health care. That would look very different from a rich and egalitarian country where cancer is one of the biggest causes of death.

Your age is correlated with brother-in-law

The calculation is complicated, but the thinking behind it is simple: when genes play a role in a trait, you have to be very similar to your siblings and parents, a little less like your cousin, less like your second cousin, and so on. Ruby and her colleagues used family tree data to explore whether the same life span between closer relatives and distant relatives. This results in estimates of heritability that are similar to those calculated previously: the life span of siblings is highly correlated, first cousins ​​are slightly correlated, and so on.

But the couple's life span is also correlated. That can be easily explained by couples who share the same household and lifestyle: eating the same healthy food or smoking cigarettes together. But the researchers saw something strange: the life span of other relatives was only related to marriage too correlated. It cannot be explained by genes, and it cannot be explained by the common environment.

So Ruby and her colleagues began investigating the life-span of in-laws. They saw the brothers-in-law, and first cousins, and then further, in relationships such as "siblings of siblings" (your sister's sister's sister) and "spouse of sibling siblings" (husband of sister your husband). Even in this far-reaching relationship, life span is correlated – if your partner lives up to old age, that means you are a little more likely to do the same.

What happens here is assortative marriage: people tend to marry people who match certain characteristics, such as education and wealth, and these traits in turn are related to longevity. This high assortative marriage rate inflated estimates of heritability on a large scale. Once they take this into account, Ruby and her colleagues get the lowest seven percent genetic influence rate – at most. That's seven percent including genetics as well as non-genetic traits, such as healthy or unhealthy habits that parents give to their children. These two things can be complicated to separate, but it is fair to assume that genetic contributions alone are even lower.

These are estimates that can change, and may already exist, because this research is based on historical data sets of people born into very different health landscapes and very different marriages. The Ancestry.com database is also populated by a large number of American families with European heritage, which limits generalizations to other groups, countries, cultures and times. But this is an important observation to think about heritability statistics in general, because assortative marriage includes all types of characteristics. There is also an assortative negative marriage, also known as "opposite pull," for internal factors.

This may seem like a disappointing result for companies interested in "the biology that controls the lifetime." But of course, the aging process and disease are still biological, even if the cause of the process is lacking in our genes than previously thought. In fact, investigating what makes the most difference in a person's life span might be precisely what produces the most interesting answers.

Genetics, 2018. DOI: 10.1534 / genetics.118.301613 (About DOI).

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