Posted on Nov 06, 2018, 9 p.m.
Family tree of millions of people shows that genetics has limited influence on longevity in a study of Ancestry.com pedigree dataset that suggests similar lifespans between spouses may have inflated previous estimates of lifespan heritability, as published in the journal GENETICS.
Long lifespans tend to run in families, but as it turns out genetics has less influence on lifespan than what was previously thought, according to analysis of more than 400 million people with results suggesting heritability of lifespan is well below past estimates that failed to account for tendencies to select partners with traits similar to our own.
Many things can be learned about the biology of aging from genetics, but if the heritability of lifespan is low it tempers expectations; it helps to contextualize the questions that scientists studying aging can effectively ask says Graham Ruby.
Heritability is a measure of how much of the variation in a trait can be explained by genetic differences as opposed to non-genetic differences. Estimates on human lifespan heritability have previously ranged anywhere from between 15-30%.
Partnering with Ancestry allowed for gaining deeper insights by using their much larger dataset than that used in any other study conducted on longevity. 54 million subscriber generated public family trees representing 6 billion ancestors were the starting point for this study. Redundant entries were removed and those from people who were still living to stitch together the remaining pedigrees by Ancestry, which also removed all identifiable information leaving only the year of birth, death, place of birth, and familial connections that make up the tree structure itself before sharing the data with the Calico research team. In all a set of pedigrees including over 400 million people who were largely Americans of European descent were involved in the study, each being connected to another by either a parent-child or spouse-spouse relationship. Using this data the team estimated heritability from this tree by examining similarity of lifespan between relatives.
Combining mathematical and statistical modeling approaches relatives focused on who were born across the 19th and early 20th centuries. Heritability estimates for siblings and first cousins were found to be similar as previously reported, and as some studies have reported lifespans of spouses tended to be correlated, in fact they were found to be more similar than in siblings of opposite gender.
Spouses correlation may be due to non-genetic factors that accompany residing in the same household and shared environments; however this started to take more shape when the team compared different types of in-laws, some of which with quite remote relationships.
First hints of something more than shared genetics or environments being at play was in finding that siblings-in-law and first-cousins-in-law had correlated lifespans despite not being blood relatives and typically not sharing households. Dataset size allowed for zooming in in longevity correlations for other more remote relationship such as all forms of in-laws, first-cousins-once-removed-in-law, and different configurations of co-siblings-in-laws. Findings of a person’s sibling’s spouse’s sibling or their spouse’s sibling’s spouse had a similar lifespan to their own made it clear that there was something else at play.
Since they don’t share genetic backgrounds or households what would best account for lifespan similarity between individuals with these types of relationships? Using the large dataset the team performed analysis to detect assortative mating, which means the factors that are important to lifespan tend to be similar between mates, more specifically people tend to select partners with traits similar to that of their own; in this case longevity.
It is hard to guess longevity of a potential mate, since you can’t really tell assortative mating in humans must be based on other characteristics which could be genetic and/or sociocultural. If income influences lifespan that may be a non-genetic example as wealthy people tend to marry other wealthy people, and genetically controlled traits would include tall people tending to marry tall people; this would lead to correlated longevity and inflate estimates of lifespan heritability.
Adjusting for these effects of assortative mating the researchers analysis found that lifespan heritability is more likely to be no more than 7%, perhaps maybe even lower. Meaning how long you live has less to do with your genes than you may think.
Materials provided by Genetics Society of America.
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Journal Reference:Graham Ruby, Kevin M. Wright, Kristin A. Rand, Amir Kermany, Keith Noto, Don Curtis, Neal Varner, Daniel Garrigan, Dmitri Slinkov, Ilya Dorfman, Julie M. Granka, Jake Byrnes, Natalie Myres, Catherine Ball. Estimates of the Heritability of Human Longevity Are Substantially Inflated due to Assortative Mating. Genetics, 2018; 210 (3): 1109 DOI: 10.1534/genetics.118.301613