Brandon LeI think I’ve found some variants in the human genome associated with human brain development, and initial excitement is giving way to worry. I’m sweating whether this or that allele will be enriched within, or – god forbid – unique to Toscani Italians, Gujarati Indians living in Houston Texas, or whoever, because I don’t think I can handle the potential internet dumpster fire. Are my anxieties misplaced? You be the judge.
I’m trying to run a genome-wide association study (GWAS), a technique that scans the length of every chromosome looking for patterns of variation that predict the presence of a trait of interest, like height or risk for schizophrenia. Done well, GWAS provides powerful and unbiased maps of genotype-phenotype relationships and can provide unbiased hints about underlying biological mechanisms. To illustrate, one GWAS for type-2 diabetes risk identified a strong association signal in variants near the KLF14 regulatory gene. Follow-up experiments at this locus described a disease mechanism whereby the GWAS-identified variants changed fat cell metabolism by modulating KLF14 gene expression.
Seasoned geneticists are quick to remind scientists-in-training like me to relax and enjoy the ongoing “golden age” where next generation sequencing technologies have produced a glut of human genetic data just waiting to be associated with just about any phenotype that can be accurately measured. We’ve logged 179,364 associations to date since the first GWAS on macular degeneration in 2005. Most of these studies don’t ruffle too many feathers, but tackling certain complex phenotypes may invite uncomfortable questions at the intersection of morality, systemic inequality, and even the extent to which our genes define our destinies. Instead of avoiding “genetic taboos”, some geneticists stick their necks out to publish findings on intelligence, educational attainment, homosexual behavior, antisocial behavior and even income.
I’m also spooked when human genetics are subjected to ignorant interpretations of “race-science”. If a geneticist is fortunate enough to utilize data from humans of diverse ancestries (read: different so-called “races”) and results suggest differences across ancestral groups, their findings might be twisted into narratives attempting to justify intolerant viewpoints. One such saga started when population geneticists detected one of the strongest-ever signatures of positive selection in variation around the gene for the enzyme that breaks down milk sugars. Variants conferring persistent lactose tolerance enjoyed success within Northern European whites whose ancestors relied on dairy-farming. Years later, white supremacists stumbled across this paper and promptly heralded the discovery of a white-specific genetic profile. Thirsty for something to worship about themselves, they started chugging milk on youtube in celebration. Of course, they failed to pay attention when similar selective signatures flagged the lactase gene in decidedly not-so-white Iranians and Eastern Africans whose ancestors also were dairy farmers. In 2020, you can see why some scientists are nervous about the lines genetics draws between people, even when they may be blurrier than ever.
I’m trying to be just the right amount of worried when I’m prepping my dataset of human genotypes from diverse ancestries. And while I’m definitely not studying anything overtly prickly like intelligence, I am studying genetics that affects human brains. My GWAS seeks to identify genetic variation affecting the growth of progenitor cells that build the cerebral cortex – the brain area responsible for fancy human cognition. If I’m lucky, I’ll find genetic variants acting as switches and dials that tweak important cellular processes in brain development, and how those variants might affect a person’s risk for neuropsychiatric disorders. I’m not studying intelligence, but some distant cellular correlate of it. Look, I just want to figure out cool things about the human brain without the science getting bastardized into Breitbart click-bait, is that too much to ask? Probably, yes. Maybe anticipating scientific misinterpretations isn’t the worst use of time. It seems at least prudent to recognize that science won’t happen in a vacuum and that our results are destined to be set adrift into the cultural milieu. The reach and rate of spread of ideas both good and bad is greater than ever. Should it then fall heavily on us to protect our science against perversion? How and where do we do so? For now, I suppose we should at least try to accompany some science, for example GWAS on kindness or COVID-19 mortality, with careful and decidedly non-sloppy discussion.
Peer edited by Dominika Trzilova