“‘Landmark’ Study Resolves a Major Mystery of How Genes Govern Human Height”, 2020-11-03 (; similar):
For height, DNA is largely destiny. Studies of identical and fraternal twins suggest up to 80% of variation in height is genetic. But the genes responsible have largely eluded researchers. Now, by amassing genome data for 4 million people—the largest such study ever—geneticists have accounted for a major share of this “missing heritability”, at least for people of European ancestry. In this group, they’ve identified nearly 10,000 DNA markers that appear to fully explain the influence of common genetic variants over height. “This is a genuine landmark”, says Daniel MacArthur of the Garvan Institute of Medical Research in Australia.
…The mystery of missing heritability dates back to the late 2000s…A number of possible explanations emerged, including rare gene variants missed by the GWA studies, gene-gene interactions, and that the twin studies were wrong. But Peter Visscher, leader of Yengo’s team, argued it was partly a matter of finding many more common variants with very small effects. He estimated that such variants should account for 40% to 50% of the genetic component of height. Picking out the faint signals would require studying the DNA of a huge number of people, however.
By 2018, Visscher’s team and other members of a global consortium called GIANT had pooled DNA data for 700,000 people and found 3,300 common markers that explained 25% of the variation in height. Now, by looking across DNA from 201 GWAS studies with 4.1 million participants, GIANT has brought the total to roughly 9,900 common markers, accounting for 40% of the variation. Other markers located nearby and likely inherited together account for another 10% of height variability. That’s still short of the 80% predicted by twin studies. But last year, Visscher’s group drew on whole-genome sequencing data of a smaller number of people to demonstrate that rare variants—those carried by fewer than one in 100 people—should explain another 30% of height’s variation. (The result was released in a March 2019 preprint that the team is revising.)
Some geneticists say they aren’t surprised that heritability gaps can be filled once enough people had their DNA scanned. “It was expected”, says Aravinda Chakravarti of New York University.