Professor Nancy Cox from Vanderbilt Genetics Institute is calling for routine adoption of inexpensive genetic tests to eliminate the bias and misdiagnosis of lab tests calibrated largely using samples from white males.
She says it’s likely to be a widespread issue for Indigenous and ethnic groups worldwide. She presented her findings at the International Congress of Genetics in Melbourne, Australia.
Many African Americans undergo painful and expensive bone marrow biopsies because they have low white cell counts – a indicator of a range of possible diseases.
But about two thirds of African-Americans have lower white cell counts than Europeans because of genetic adaptations that reduce risk of malaria, so the lab test is really just confirming that they have ancestors from areas with endemic malaria.
Cox and her team are studying how lab tests for kidney disease, white cell counts, and other chronic conditions can lead to underdiagnosis and failure to treat or overdiagnosis and unneeded treatments due to the longstanding use of relatively small numbers of samples from white men used to establish reference ranges for lab tests.
“There was no ill will, no intent to do bad medicine, people just haven’t allowed for the diversity of humanity.”
Indigenous Australian Professor Alex Brown suggests that this is just one example of where the lack of appreciation and application of genomic variation across populations can lead to adverse outcomes for many communities. “Despite the increasingly central role of genomics in modern healthcare and biomedical research, the failure to understand diversity remains a key roadblock to ensuring all populations can benefit from what precision medicine could and should offer.” Professor Brown leads the new Australian Alliance for Indigenous Genomics (ALIGN).
Māori researchers Associate Professor Phillip Wilcox of the University of Otago says that about half the Māori they tested in one of their studies had a variant of a gene which meant that the prescription of any one of six commonly prescribed drugs would need to be changed. Some variants were much more common than what is typically observed in European populations on which most prescribing recommendations are based.
"I don't even know what to call this kind of disparity," says Cox. "It's not that these genetic variations are directly leading to disease, it is more a failure to understand the consequences of genetic diversity."
“Fundamentally we need to understand that humans are diverse, and we need to develop reference ranges for tests that reflect our diversity,” she says.
Cox is advocating 'individualised ranges'. This means that when you go to see your physician for some bloods, the numbers you get back will be assessed using scales calibrated just for you, based on your sex and age - but also, crucially, on your genetics.
But with medical systems under strain, we can't afford to add more labour to a doctor's day. Vanderbilt wants to develop protocols that will make bespoke tests quick and easy to administer.
"There are no simple solutions to complex problems," said Cox. "[But] we can't go on with our medical centre juggernaut... we ignore icebergs at our peril."
This press release is based on a plenary presenatation by Cox at the International Congress of Genetics in Melbourne, Australia on 21 July 2023. Brown and Wilcox also spoke at the Congress.