Where Your Ancestors Lived—More Than Your Race—May Explain Key Health Disparities

As a shy undergraduate at Harvard University in the late sixties, Constance Hilliard butted heads with the stodgy chairman of the history department. Convinced that there were untold stories buried in her ancestry that could yield far-reaching insights, she told the prominent historian that she wanted to major in African history. “But Africa doesn’t have a history,” she remembers him responding.

Hilliard knew that not only does Africa possess a rich and varied history, but it’s also the origin of all human history. Because the first Homo sapiens evolved there and migrated across the globe, our genome can be traced to the continent. The late sixties were a period of social upheaval, and Hilliard believed that a greater understanding of the interplay of African and American history could help address contemporary social issues in the United States.

Decades later, now a professor of history at the University of North Texas, Hilliard continues to pursue such lines of inquiry. In her newly published book, Ancestral Genomics: African American Health in the Age of Precision Medicine, she mines her decades of research to reveal remarkable findings, with practical implications, about the genetic and ecological roots of some of the most persistent issues plaguing American medicine.

Hilliard sees a “direct connection” between gaps in historical knowledge and “the medical community’s understanding of African American health.” As disproportionate mortality rates during the COVID-19 pandemic laid bare, the odds are often stacked against Black Americans in our country’s health-care system. Higher rates of hypertension, diabetes, and death from heart disease among Black Americans help explain why non-Hispanic white Americans live almost five years longer on average. Infant and maternal mortality rates are two and three times higher, respectively, for Black Americans compared to their white peers.

Hilliard’s inspiration for writing Ancestral Genomics grew out of a diagnosis she received in 2008, while spending a year in Japan as a Fulbright visiting scholar in the hilly coastal town of Nishihara. She’d been experiencing hip pain, so she went to see a Japanese doctor, who ordered a comprehensive medical exam, including blood tests. The joint pain could be explained by arthritis and was treatable, the doctor told her, but he had noticed something troubling in the lab reports. “You appear to be suffering from kidney failure,” he said.

This was the first Hilliard had heard of any trouble with her kidneys. When she returned to the U.S. a couple of weeks later, her primary care physician in Texas assured her there was nothing wrong with her kidneys. “I was in a very emotional place,” Hilliard recalls. “I was so relieved there was nothing wrong with me, but at the same time, I was genuinely confused, because he had showed me the fact that he had checked off African American on my lab forms, meaning that there was some special algorithm for African Americans.”

Though it had apparently helped clear up Hilliard’s misdiagnosis, such race-based algorithms—in this case, one that assumed that the normal range of the chemical waste product creatinine is higher in Black patients than in non-Hispanic white patients—have drawn criticism for not being based on sound science and for exacerbating health disparities. What’s more, Hilliard had been teaching her students for decades that race is a social construct, but here was a doctor saying that her race explained her diagnosis. The situation left her puzzled, and it sent her back to African manuscripts she’d studied as a young historian. “This was a narrative that could only be elucidated if a transdisciplinary approach involving historical and ecological knowledge was applied to the medical science,” she writes in Ancestral Genomics.

Hilliard had spent much of her early career studying the important medieval trade center of Timbuktu, located in interior West Africa, in what is Mali today. The city was home to a prosperous society that drew much of its wealth from the exchange of gold and salt, along trade routes that extended from sub-Saharan Africa to Europe. After convincing her Harvard professors to allow her to follow her academic passions, Hilliard had pored over ancient manuscripts from the region, translating the texts and deciphering buried clues from the past. When reconsidering the material shortly after her 2008 misdiagnosis, one of her important discoveries was that “it is not the gold that offers insights into Black health but rather the commodity that was so desperately scarce in the African interior that its elites readily traded their gold to obtain it—salt.”

For countless generations before the gold-salt trade emerged, the humans living in this region had evolved to subsist on a tiny fraction of the sodium consumed by their peers on the salt-rich coasts. Because the majority of Africans cast into American slavery came from the salt-poor interior of the continent, Hilliard writes, many Black Americans today likewise have much lower sodium needs than do their non-Black neighbors. The test that alarmed Hilliard’s Japanese doctor found elevated levels of creatinine, but research in the U.S. has found that these elevated levels can be normal among African Americans. That’s why physicians in the U.S. (unlike in Japan) adjust the “normal” range of creatinine in patients who self-identify as African American. But, according to Hilliard, it’s not the race of patients that doctors should take into account—it’s their specific ancestry.

Hilliard argues that the elevated creatinine levels found in many African Americans may be an indication of kidneys that evolved to survive in a salt-poor ecological region. An African American whose ancestors hail from, say, coastal Nigeria likely wouldn’t have the same creatinine levels. Hilliard references studies that have consistently found salt sensitivities in African Americans, which—when paired with the salt-heavy contemporary American diet—have led to higher blood pressure and increased rates of heart disease and kidney failure.

But Hilliard writes that, despite this evidence, “current medical research simply overlooks the unique ecological conditions of American Blacks’ genetic ancestry.” Focusing instead on social factors that may have an impact on heath, “millions of dollars are allocated to studies that continue to attribute this population’s salt-sensitive hypertension and kidney failure solely to stress resulting from racism,” she writes.

Hilliard traces these salt sensitivities to the APOL1 gene variant. She writes that if, through genetic testing, medical professionals can identify the patients who carry this gene, they can then make dietary and lifestyle recommendations that account for the genetic predisposition.

As she dug further into the ecological conditions unique to interior West Africa, Hilliard came to her next big revelation—this one involving dairy products. In parts of West and Central Africa’s “tsetse belt” today, 99 percent of the inhabitants are lactose intolerant. The tsetse fly endemic to the region carries a pathogen that causes a wasting disease in cattle. Until recently, it was virtually impossible to maintain a healthy herd of cattle there. “This harsh ecological environment accounts for the fact that West African food culture is devoid of dairy products,” Hilliard writes.

For millennia, those who lived in this region got by without milk. Hilliard makes a convincing case that the lactose intolerant genes persist in many African Americans and may be responsible for factors such as the prevalence among young Black women of the particularly aggressive triple-negative form of breast cancer. (Hilliard’s own mother died of breast cancer when she was just 51 years old.) Hilliard discovered that genetic researchers had found a gene variant among those of African descent (TRPV6a) that may account for higher calcium retention and higher prevalence of certain cancers, including triple-negative breast cancer and a severe form of prostate cancer.

From this information, Hilliard concluded that severe health disparities among racial groups in America may be explained, in large part, by inexact dietary guidelines for salt and dairy products. Rather than dividing patients into groups based on race, Hilliard writes that we should focus instead on what she calls ecological niche populations. Patients whose ancestors evolved in the same area will likely have similar genetic profiles and similar dietary needs and sensitivities. Hilliard recommends that doctors be equipped to consider such factors in developing guidelines on dietary calcium and sodium intake, as well as kidney transplant eligibility.

Linda Dairiki Shortliffe, a urologist and professor emerita at Stanford University’s medical school, says the implications of Hilliard’s research may extend well beyond salt and dairy products. She suspects genetic factors such as the ones Hilliard discusses in the book also play a major role in how the body metabolizes medicines. Shortliffe was a Harvard classmate of Hilliard’s and was surprised, years ago, to find the historian’s name in medical literature related to prostate cancer, one of Shortliffe’s areas of expertise early in her career.

Shortliffe describes Ancestral Genomics as a revelatory book. It demonstrates, in a way she hadn’t understood before, that so much of what we know about human health is based on the genetic data of those with European ancestry, which has fostered a system of care tailored to only one portion of the population. “I think the more that we find out about how both nutrition and drugs work, we’re finding that that is entwined with our basic genome,” she says.

While medicine is increasingly considering the distinct genetic profiles of patients of differing ancestral backgrounds, Debra Murray, a researcher in the molecular and human genetics department at Baylor College of Medicine, in Houston, concedes that “it’s a big issue” that hasn’t been adequately addressed. Hilliard’s book, she says, may help lead to practical medical guidelines for patients of African ancestry, who often face more obstacles and bleaker prognoses in the American health-care system. “The importance really is treating people,” she says.

Shortliffe notes that clinical trials need to be run to test the book’s conclusion that patients of interior West African ancestry should consider reducing dairy and sodium in their diets. She cautions that anyone who plans to make significant changes to what they drink or eat should first discuss it with their physician.

For Hilliard, the research has already informed her daily life. She has adjusted her diet in recent years. We’re animals, after all, she says, and we evolved to live and eat in ways specific to the ecosystems our forebears inhabited. She’s wary of overindulging in salt and dairy. She has also cut out meat from her diet, and she’s increased the amount and variety of vegetables she eats. She says much of her decades of complex research can be boiled down to a simple piece of advice: “Honor the staples and the food culture of our ancestors.”