Ethnicity, At its Heart

Ethnicity, At Its Heart Sonia Anand helped pioneer the largest study of heart risks worldwide—and couldn't believe what she found. Sonia Anand was perplexed. In 1997, the epidemiologist and MD at McMaster University found that when South Asians move to Canada, their risk of heart attack mysteriously spikes. Though heart disease is the number-one killer worldwide, the rate is 4 percent in rural India. When South Asians live in Canada, the rate jumps to 11 percent, which is double that of their white neighbors and almost six times as great as Chinese Canadians. Anand theorized that something in their new country is upping their chances for a heart attack. It could be the shift to a fattier Western diet or new stressors in the lives of immigrants. But the fact that the same environment affects different ethnic groups in different ways had Anand asking a far broader question. At least when it comes to heart disease, whites have been far overrepresented in the epidemiological literature, she says. She suspected that if nonwhites were subject to the same number of epidemiological studies, the statistics and risk factors might look very different. To answer that question, her advisor, world-renowned cardiologist and epidemiologist Salim Yusuf, launched a 52-country investigation called the INTERHEART Study that engaged hundreds of researchers worldwide. Anand took charge of the genetic portion of the investigation. And after 5 years, their findings came as a surprise. In some ways, Anand’s entire life had anticipated this moment. Of Indian descent, her parents moved from practicing medicine in Nigeria to practicing in a small town on the east coast of Nova Scotia in 1965. The family was among a handful of ethnic Indians living in the entire province. Her parents worked as a duo in the local hospital, her mother as an anesthesiologist and her father as a general surgeon. On busy days, Anand and her two older sisters would visit them in the cafeteria to eat Jell-O and stale sandwiches. “I don’t like hospital food to this day,” she jokes. Over lunch, however, her parents would tell stories of their practice in Africa and about the severe yet preventable diseases they treated. It sparked Anand’s desire to follow suit. “Growing up, we had this sort of global perspective of the world,” Anand says. When she began studying medicine at McMaster, she sought out a mentor who would foster her broad worldview. She found Yusuf, who had just come to the university from the US National Institutes of Health. He sent her to Bangalore on her first epidemiological study to compare the ways emergency room doctors treat heart attacks in Hamilton, Ontario and Bangalore. It turned out that Indian doctors were far faster at administering treatments. In response, Hamilton created an ER fast-track for patients with chest pains. Having seen how her research could save lives, Anand was hooked. She earned a PhD in epidemiology alongside her MD specializing in internal and vascular medicine. “I remember Sonia as a medical student,” says Hertzel Gerstein, a colleague and professor in the department of clinical epidemiology and biostatistics at McMaster. “People don’t change. People who are energetic, engaging, enthusiastic, and passionate when they’re young tend to stay that way as they get older, and she’s no exception.” Yusuf and Anand began their international study on the risk factors for heart attack among different ethnic groups in 1999. They tracked 30,000 people in communities around the world. Some 37 international organizations helped pay the initial $10 million bill. Since then, there’s never been a study of its scope. “INTERHEART really is the largest study that has a global perspective. I think other studies are evolving to do what it has done, but I don’t think they’ll really match it,” says Jaime Engert, a genetic epidemiologist at McGill University who worked on the study. The study proved that ethnicities worldwide share the same nine risk factors for heart disease. Cholesterol, diabetes, blood pressure, abdominal obesity, smoking, stress, exercise, diet, and alcohol accounted for 90 percent of heart attacks. The findings came as a revelation: though some groups were more susceptible to one factor or another (for example, Indians are prone to diabetes and the Chinese more likely to smoke cigarettes), no group showed novel risk factors. "Sonia always says, 'ethnicity is not just genes.' It's a reminder that it's also your cultural heritage," says Jaime Engert at McGill University. Anand spent the next 6 years analyzing the genes in her blood samples to understand how genetics among ethnicities play a role in heart disease. Within 103 genes, she genotyped 1,536 single nucleotide polymorphisms (SNPs) and associated 13 common SNPs with heart disease. Most relate to the way the body processes low-density lipoprotein (LDL) cholesterol. Four are responsible for producing apolipoprotein B, which carries cholesterol to the tissues in the body. Only one SNP has a direct relation to heart attack. Together, the genetic factors she tested increase the risk of heart attack by only 1.6 percent. The findings were extremely encouraging, she says. Factors that can’t change, like genetics, play a far smaller role than factors that can change, like behavior. The risk factors, however, doubly endanger South Asians. Not only do they suffer higher rates of diabetes, but the cutoff for a healthy body mass index (BMI) is 21, four points and 24 pounds less than the average white person. At that threshold, BMI starts to compound other risk factors, like blood pressure and cholesterol. Anand calls it the “Canadian tire.” And changes in lifestyles—not just in Canada, but in an urbanizing India—account for a lot of the problem. “I’ve been doing genetics for a long time, and we’re very interested in our ability now to have an accurate understanding of someone’s ethnicity through the genes,” says Engert. But “Sonia always says, ‘ethnicity is not just genes.’ It’s a reminder that it’s also your cultural heritage, the food you eat at home, the likelihood that you smoke or drink alcohol. These have a powerful cultural influence as well as a genetic influence.” Anand next plans to use the DNA samples from the INTERHEART study to investigate how genetics and environment interact to affect heart disease. “I’m known as a traditional epidemiologist who happens to understand genetics,” says Anand. “People had high hopes for the promise of genetics to help prevent and cure disease. But when you look at it, the classical public-health person might say, ‘What’s the big deal with your very expensive genetics research? You’ve only shown that they add a small predictive value.’ Having said that, we’ve only studied 100 genes and there are 30,000 in the human genome. We have a lot of work ahead of us.”

Ethnicity, At its Heart

Ethnicity, At Its Heart

Sonia Anand helped pioneer the largest study of heart risks worldwide—and couldn't believe what she found.

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Daniel Grushkin

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December 2010

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