Sunday, April 21, 2024

Genes play a very small role in determining left-handedness

I am left-handed

NPR's Ayesha Rascoe speaks with Clyde Francks, a geneticist in the Netherlands, about the latest research into what makes people left or right-handed.


If you're left-handed, like me, you know you are one of a rare and special breed. Just 10% of the world's population is estimated to be left-handed, but many common conceptions about left-handedness turn out to be wrong, starting with that it's definitely hereditary.

CLYDE FRANCKS: We actually think that most of the left-handedness in the population is not caused by genetic variants.

RASCOE: Clyde Francks is a geneticist and neuroscientist at the Max Planck Institute for Psycholinguistics in the Netherlands. He led a team that just published a paper about left-handedness in the journal Nature Communications.

FRANCKS: It's probably just kind of random fluctuations of chemicals in the very early developing brain in the embryo.

RASCOE: That surprised me. My mother's right-handed, but all of her children are left-handed. We thought being left-handed must have something to do with the genes we inherited. And it's even stranger because we don't all have the same father.

FRANCKS: The heritability of left-handedness is actually quite low. So in studies of twins, it's been measured at about only 25%. So in most people who are left-handed, there will not be a simple genetic explanation just running through the generations in a clear way.

RASCOE: But in the new research, Francks and his team did discover one gene that sometimes has an effect on which hand is dominant.

FRANCKS: What we knew before this study was that there were various common variants in the genome that had very, very tiny effects on the probability of being left-handed. And so what we did in the latest study was a quite different approach. We were looking for variants in the genome that are very rare in the population and are located in the specific parts of the genome that code directly for the proteins that our bodies are made of. And those kinds of genetic variants can actually have quite large effects on human traits when they're present in a small number of people.

RASCOE: The gene they analyzed is called TUBB4B. If someone has a particular variant of this gene, Francks says that person is very likely to be left-handed. But very few people, even very few left-handed people, have this variant.

FRANCKS: They're very rare in the population, so they would only be accounting for about 1 in 1,000 left-handers at most.

RASCOE: It's still very much a mystery why the vast majority of left-handed people are that way. His idea about random fluctuations of chemicals in the embryo is also unproven. But what about this question?

I've also heard that left-handed people are more creative because the left side of the body's controlled by the right side of the brain, and that's the creative side. Is that true?

FRANCKS: Yeah. I mean, I don't think that's true. No.

RASCOE: (Laughter).

FRANCKS: I know that this is - it's a popular thing. That's too simple. The differences between the hemispheres of the brain are much more subtle and complex than that, and each side is doing important things in any particular task that you're doing.

RASCOE: OK, so - but we are very special if we're left-handed. Science has confirmed that, right?


FRANCKS: Well, 10%, you know? You decide how special that is.

RASCOE: Oh, well, thank you. I appreciate that. I'll take that. Thank you so much. Clyde Francks, a geneticist at the Max Planck Institute for Psycholinguistics in the Netherlands. Thank you so much for joining us.

FRANCKS: Thank you.

Schijven D, Soheili-Nezhad S, Fisher SE, Francks C. Exome-wide analysis implicates rare protein-altering variants in human handedness. Nat Commun. 2024 Apr 2;15(1):2632. doi: 10.1038/s41467-024-46277-w. PMID: 38565598; PMCID: PMC10987538.


Handedness is a manifestation of brain hemispheric specialization. Left-handedness occurs at increased rates in neurodevelopmental disorders. Genome-wide association studies have identified common genetic effects on handedness or brain asymmetry, which mostly involve variants outside protein-coding regions and may affect gene expression. Implicated genes include several that encode tubulins (microtubule components) or microtubule-associated proteins. Here we examine whether left-handedness is also influenced by rare coding variants (frequencies ≤ 1%), using exome data from 38,043 left-handed and 313,271 right-handed individuals from the UK Biobank. The beta-tubulin gene TUBB4B shows exome-wide significant association, with a rate of rare coding variants 2.7 times higher in left-handers than right-handers. The TUBB4B variants are mostly heterozygous missense changes, but include two frameshifts found only in left-handers. Other TUBB4B variants have been linked to sensorineural and/or ciliopathic disorders, but not the variants found here. Among genes previously implicated in autism or schizophrenia by exome screening, DSCAM and FOXP1 show evidence for rare coding variant association with left-handedness. The exome-wide heritability of left-handedness due to rare coding variants was 0.91%. This study reveals a role for rare, protein-altering variants in left-handedness, providing further evidence for the involvement of microtubules and disorder-relevant genes.

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