Tagged Genetics and Heredity

Weight Has Greater Impact on Diabetes Than Heart Disease


Carrying excess weight may have a greater impact on the risk for diabetes than it does on the risk for heart disease or early death, a new study has found.

To look at the effect of obesity independent of genetics, Swedish researchers followed 4,046 pairs of identical twins whose average age was 58. One of the twins was overweight, and the other was not. Since identical twins have the same genes, their weight difference could not be attributed to genetics. The study is in JAMA Internal Medicine.

After accounting for physical activity, smoking and educational level, the researchers found that having a higher body mass index, or B.M.I. — even among those in the obese range of 30 or higher — was not associated with an increased risk for heart attack or death. But a high B.M.I. was associated with an increased risk for diabetes.

“Based on these results, the association between obesity and cardiovascular disease is explained by genetic, not environmental, factors,” said the lead author, Peter Nordstrom, a professor of geriatric medicine at Umea University. “Unfortunately, this also means that environmental factors that reduce obesity do not reduce the risk of cardiovascular disease or death. But they most certainly decrease the risk for diabetes.”

For Coffee Drinkers, the Buzz May Be in Your Genes


Credit Andrew Scrivani for The New York Times

Like most of my work, this article would not have been possible without coffee.

I’m never fully awake until I have had my morning cup of espresso. It makes me productive, energized and what I can only describe as mildly euphoric. But as one of the millions of caffeine-loving Americans who can measure out my life with coffee spoons, (to paraphrase T.S. Eliot), I have often wondered: How does my coffee habit impact my health?

The health community can’t quite agree on whether coffee is more potion or poison. The American Heart Association says the research on whether coffee causes heart disease is conflicting. The World Health Organization, which for years classified coffee as “possibly” carcinogenic, recently reversed itself, saying the evidence for a coffee-cancer link is “inadequate.” National dietary guidelines say that moderate coffee consumption may actually be good for you – even reducing chronic disease.

Why is there so much conflicting evidence about coffee? The answer may be in our genes.

About a decade ago, Ahmed El-Sohemy, a professor in the department of nutritional sciences at the University of Toronto, noticed the conflicting research on coffee and the widespread variation in how people respond to it. Some people avoid it because just one cup makes them jittery and anxious. Others can drink four cups of coffee and barely keep their eyes open. Some people thrive on it.

Dr. El-Sohemy suspected that the relationship between coffee and heart disease might also vary from one individual to the next. And he zeroed in on one gene in particular, CYP1A2, which controls an enzyme – also called CYP1A2 – that determines how quickly our bodies break down caffeine.

One variant of the gene causes the liver to metabolize caffeine very quickly. People who inherit two copies of the “fast” variant – one from each parent – are generally referred to as fast metabolizers. Their bodies metabolize caffeine about four times more quickly than people who inherit one or more copies of the slow variant of the gene. These people are called slow metabolizers.

With funding from the National Institutes of Health, Dr. El-Sohemy and his colleagues recruited 4,000 adults, including about 2,000 who had previously had a heart attack. Then they analyzed their genes and their coffee consumption. When they looked at the entire study population, they found that consuming four or more cups of coffee per day was associated with a 36 percent increased risk of a heart attack.

But when they split the subjects into two groups – fast and slow caffeine metabolizers – they found something striking: Heavy coffee consumption only seemed to be linked to a higher likelihood of heart attacks in the slow metabolizers.

“The increased risk that we saw among the entire population was driven entirely by the people that were slow metabolizers,” said Dr. El-Sohemy, who is also on the science advisory board at Nutrigenomix, a personalized nutrition company. “When you look at the fast metabolizers, there was absolutely no increased risk.”

The trend among fast metabolizers was quite the opposite. Those who drank one to three cups of coffee daily had a significantly reduced risk of heart attacks – suggesting that for them coffee was protective.

Dr. El-Sohemy suspects that because caffeine hangs around longer in a slow metabolizer, it has more time to act as a trigger of heart attacks. But fast metabolizers clear caffeine from their systems rapidly, allowing the antioxidants, polyphenols and coffee’s other healthful compounds to kick in without the side effects of caffeine, he said.

Other more recent research seems to point in the same direction. In Italy, a team of scientists looked at hypertension in 553 fast and slow caffeine metabolizers. Once again, the subjects’ genetic profiles predicted whether coffee was potentially harmful or healthful. Heavy and even moderate coffee drinkers were significantly more likely to have hypertension if they were slow metabolizers. But fast metabolizers saw their risk of hypertension fall as their coffee intake rose.

That is not to say that every coffee drinker should run out and have their CYP1A2 genes analyzed by one of the many direct-to-consumer genetic testing companies. Dr. Marilyn Cornelis, an assistant professor at the Northwestern University Feinberg School of Medicine, said her research had identified many genes involved in caffeine metabolism, and that relying on only one or two genetic factors could provide people with a false sense of reassurance.

“There are clearly other genetic and environmental factors contributing to differences in caffeine metabolism,” she said. “And these are not captured by existing tests.”

Nonetheless, this greater understanding of the link between coffee and genetics has opened up a wide new area of research. Scientists are now studying whether the CYP1A2 gene and others might mediate coffee’s influence on breast and ovarian cancer, Type 2 diabetes and even Parkinson’s disease.

It has also prompted a closer look at the effects of caffeine on exercise. Though it has long been accepted that caffeine enhances sports performance, research by Christopher J. Womack, a professor of kinesiology at James Madison University, suggests that endurance athletes who are fast caffeine metabolizers may benefit more than others.

In one study in 2012, Dr. Womack and his colleagues studied the effect of caffeine pills and placebos on the performance of male cyclists. Dr. Womack found that the slow metabolizers completed a 40-kilometer race on a stationary bike one minute faster on caffeine. But the fast metabolizers improved their time by four minutes.

Dr. Womack suspects that the fast metabolizers saw greater benefits because the rapid metabolism of caffeine further heightened their sympathetic nervous systems — which control the so-called fight or flight response.

“In the broad sense, the average person is going to perform better with caffeine,” he said. “Some people have a huge effect. Not surprisingly, it has something to do with our genetics.”

As an avid coffee consumer, I was curious about my own genes. Through a company called FitnessGenes, which analyzes 41 different genes related to diet and exercise – including CYP1A2 – I learned that I was a so-called fast caffeine metabolizer. The company says that 40 percent of people are fast metabolizers. About 45 percent have both a slow and a fast copy, and 15 percent carry two copies of the slow allele.

Dan Reardon, a medical doctor who founded FitnessGenes, said that, anecdotally, slow metabolizers who drink coffee tend to report a very gradual wakefulness, sometimes lasting hours. But fast metabolizers often experience something very different with coffee: an immediate spike in alertness followed at times by a relatively quick dip in energy.

While my DNA results suggested that my twice-daily espresso habit might be for the best, researchers have only just begun to understand how our genes and coffee habits interact. In a 2015 study, Dr. Cornelis and a team of international scientists identified eight genetic variants that appear to make people more likely to seek out coffee, including at least two variants that are involved in the psychologically rewarding effects of caffeine.

The research could help to explain why some people see little or no appeal in a freshly brewed cup of coffee – while others, like me, can hardly fathom a morning without it.

Eat Well is a new weekly column on the science and culture of eating.

To Stem Obesity, Start Before Birth


Credit Paul Rogers

To stem the current epidemic of obesity, there’s no arguing with the adage that an ounce of prevention is worth a pound of cure. As every overweight adult knows too well, shedding excess pounds and keeping them off is far harder than putting them on in the first place.

But assuring a leaner, healthier younger generation may often require starting even before a baby is born.

The overwhelming majority of babies are lean at birth, but by the time they reach kindergarten, many have acquired excess body fat that sets the stage for a lifelong weight problem.

Recent studies indicate that the reason so many American children become overweight is far more complicated than consuming more calories than they burn, although this is certainly an important factor. Rather, preventing children from acquiring excess body fat may have to start even before their mothers become pregnant.

Researchers are tracing the origins of being overweight and obese as far back as the pre-pregnancy weight of a child’s mother and father, and their explanations go beyond simple genetic inheritance. Twenty-three genes are known to increase the risk of becoming obese. These genes can act very early in development to accelerate weight gain in infancy and during middle childhood.

In the usual weight trajectory, children are born lean, get chubby during infancy, then become lean again as toddlers when they grow taller and become more active. Then, at or before age 10 or so, body fat increases in preparation for puberty – a phenomenon called adiposity rebound.

In children with obesity genes, “adiposity rebound occurs earlier and higher,” said Dr. Daniel W. Belsky, an epidemiologist at Duke University School of Medicine. “They stop getting leaner sooner and start putting on fat earlier and put on more of it.”

Still, twin and family studies have shown that many children with these genes remain lean. Furthermore, these same genes were undoubtedly around in the 1960s and 1970s when the obesity rate in children was a fraction of what it is today.

So what is different about the 2000s? Children today are surrounded by a surfeit of unwholesome, easy-to-consume calorie-dense foods and snacks accompanied by a deficit of opportunities to expend those extra calories through regular physical activity. And countering a calorie-rich, sedentary environment is now harder than it should be, with the current heavy emphasis on academics, parental reluctance to let children play outside unattended, and intense competition from electronics. All these circumstances may give obesity genes a greater chance to express themselves.

“There is no going back to a world in which calories are scarce and obtaining them is physically demanding,” Dr. Belsky wrote in an editorial in JAMA Pediatrics. “And governments and their publics have shown little enthusiasm for regulations restricting access to palatable, calorie-dense foods.”

Curbing consumption of sugar-sweetened beverages and keeping calorie-dense junk food out of the house and other settings where young children spend time is crucial. This is especially important for infants and children with large appetites that are not easily satisfied.

It’s also essential that parents model good eating habits, experts agree. “If you do it, they’ll do it,” David S. Ludwig, an obesity specialist at Children’s Hospital Boston, said. “Young children are like ducklings, they want to do what their mothers do.”

Equally important, Dr. Belsky said, is “allowing children in institutional settings – in day care, preschool and elementary school – to be as active as they choose to be rather than forcing them to sit quietly in chairs most of the day. Being physically active encourages a healthy metabolism. Active children are not constantly hungry.”

He added, “In the face of the obesity epidemic, eliminating the handful of opportunities for kids to be active during the day is a shame. Sedentary behavior becomes a life pattern.”

Another critical issue is the vicious cycle of overweight that starts with future mothers and fathers who are overweight or obese. “If we want healthy kids, we need healthy moms before pregnancy and during pregnancy,” Dr. Belsky said. “There are multiple pathways by which unhealthy levels of weight before and during pregnancy can influence a child’s weight going forward.”

As Dr. Ludwig explained, “Although genes are not modifiable, the weight of the mother before and during pregnancy is. Excessive weight gain during pregnancy predicts not just the baby’s birth weight but also the likelihood of obesity in middle childhood.”

The father’s weight is also turning out to be important, Dr. Ludwig said. “Acquired factors influence gene expression,” he said. “Being heavy alters DNA in the father’s sperm that changes gene expression and can be passed down to the next generation.”

Most, though not all, studies have linked a longer duration of breast-feeding to a reduced risk of overweight in children. Although Dr. Ludwig said that the effect “is not dramatic,” a more important benefit of breast-feeding may be “exposing the baby to a wider range of tastes based on what a mother is eating. If a breast-feeding mom eats a large variety of nutritious foods, the child is more likely to like them.”

Antibiotics given early in life, however, may counter any potential benefits of breast-feeding for weight gain, a new study found. Researchers at the University of Helsinki in Finland reported that when breast-fed infants are treated with antibiotics, the antibiotics kill off health-promoting bacteria that live in the gut. “The protective effects of breast-feeding against infections and overweight were weakened or completely eliminated by early-life antibiotic use,” the team wrote in JAMA Pediatrics last month.

Even if children have already started on a path of poor eating habits and excess weight gain, Dr. Ludwig said it is not too late to make healthful changes. As founder of the Optimal Weight for Life program and author of “Ending the Food Fight: Guide Your Child to a Healthy Weight in a Fast Food/Fake Food World,” he advocates an authoritative, but not an authoritarian, parenting style that eliminates stress and conflict over what and when a child eats.

“Never force food on a child,” he insists. “Stand your ground in a gentle but firm way and be prepared to do a little negotiating. When a child refuses to eat the dinner that’s served, put it away in the fridge to be eaten later. If the child says ‘I’m not going to eat it,’ the response should be, ‘Fine, just go to bed,’ not ‘O.K., I’ll make you mac and cheese.’

“Children should be allowed to control their bodies, but parents have to provide the guidance and control the environment,” Dr. Ludwig said.

This is the second of two columns on childhood obesity. Read the first: “The Urgency in Fighting Childhood Obesity.”


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Does Exercise During Pregnancy Lead to Exercise-Loving Offspring?


Credit Getty Images

Mice born to mothers that run during their pregnancies grow up to be rodents that love to run as adults, according to a thought-provoking new animal experiment, while pups with sedentary moms had a less-enthusiastic attitude toward exercise. Though it’s a long way from mice to people, the study’s findings hint at the possibility that to some extent our will to work out may be influenced by a mother’s exercise habits during pregnancy, and begin as early as in the womb.

Most of us have probably observed that activity patterns tend to run in families, a situation that has been confirmed in studies involving both people and animals. Children whose parents are sedentary often tend to be inactive themselves, whereas parents who are physically active typically have children who move around and exercise often.

Logically, home environment and nurture influence familial activity levels; children learn from and mimic their parents.

Recent science, however, suggests that there are other, deeper biological influences at work as well, including genetics. A number of studies have identified various snippets of DNA that, if someone carries them, predispose that person to be quite active, while other gene variations may nudge someone toward being a couch potato.

But scientists also have begun to wonder about the role of a process known as developmental programming. According to this theory, a growing baby’s body and its very DNA can be changed by the environment it experiences in the womb and immediately after birth. These changes may, in turn, affect lifelong health and disease risk. Mouse pups born to mothers that become overweight and metabolically unhealthy during pregnancy, for instance, are more likely to be overweight and diabetic as adults than genetically identical mice born to mothers that maintain a normal weight during pregnancy.

To what extent developmental programming might affect someone’s willingness to work out, though, had rarely been explored.

So for the new study, which was published this month in the FASEB Journal, researchers from Baylor University and Rice University in Houston gathered genetically identical female mice and put them in cages with running wheels. Mice like running, and most of these animals jogged about six miles a day. After a week with wheels, the females were matched with male mice from the same genetic line. Pregnancies ensued.

At that point, half of the pregnant mice had their running wheels locked so that they could not run freely during pregnancy.

The other mice were allowed to continue running at will throughout their pregnancies, and they did keep running, although their distance and speed declined as they grew heavy with young.

After the babies were born and weaned, the pups were removed to their own cages, without wheels. Their cages were separated from those of the adult mice, so the young mice would not have watched their mothers working out and tried to emulate them.

But at multiple points throughout their lives, this second generation of mice was moved for several days to special cages equipped with unlocked running wheels and monitors that tracked how much they moved when not on the wheels.

During the pups’ childhoods, the scientists noted few differences in exercise behavior between the young mice. But as the animals entered adolescence, those born to running moms started to become enthusiastic runners themselves, putting in more miles on the wheels than the other mice and moving around more frequently in their cages when they were not running.

These differences accelerated as the animals aged, so that during the rodent equivalent of middle age, the animals born to runners were running and moving around significantly more throughout the day than the other mice, even though all of them were genetically the same and had had identical upbringings.

The clear implication of these results is that “a mother’s physical activity during pregnancy likely affects the physical activity of her offspring,” said Robert Waterland, a professor of pediatrics and genetics at Baylor who led with study with his colleagues Jesse Eclarinal and Shaoyu Zhu.

In essence, baby mice with active moms had literally been born to run.

Of course, mice are not people, and this study can’t tell us whether similar programming occurs in our babies if we are active during pregnancy.

The study also can’t explain how exercise during pregnancy affects a developing infant’s later urge to work out. It may be, Dr. Waterman said, that the mother’s physical movements jiggle the womb slightly in ways that alter fetal brain development in parts of the brain devoted to motor control and behavior; or that certain biochemicals produced by the mom during exercise pass through the placenta, affecting the baby’s physiology and gene activity lifelong.

He and his colleagues hope to study those issues in future experiments.

But for now, he said, it’s important that no mother interpret these results as a criticism if she didn’t exercise much during pregnancy. Those of us who have borne children know how exhausting the experience can be. But, he said, if a pregnant woman — with her doctor’s blessings — can walk, jog, swim or otherwise be physically active, she may improve her own health and also, just possibly, instill an incipient love of exercise in the child growing within her.


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Meeting My DNA


Marie Tae McDermott and her dog, Cody, at Bushwhick Inlet Park in Brooklyn.

Marie Tae McDermott and her dog, Cody, at Bushwhick Inlet Park in Brooklyn.Credit Andrew Renneisen for The New York Times

I was adopted when I was 6 months old, so I don’t know much about my family medical history. I don’t know, for example, whether I’m at increased risk for breast cancer, heart disease, mental illness. But home DNA testing is changing all that.

The tests are sent through the mail, no lab visits required. And they’re not limited to the human genome.

I tested the DNA waters with Cody, my four-legged adoptee. After shelling out $69 for a Wisdom Panel DNA test kit, I swabbed the inside of Cody’s cheek with a cotton swab from the kit and dropped it in the mail. Six weeks later I received Cody’s genealogy chart by email. While I’d always considered him pure mutt, with his apple-shaped head and stocky middle, results showed an uninterrupted lineage of Chihuahuas going back three generations.

I could only hope for such clarity. I ordered a kit from 23andMe, one of a handful of companies that now offer home testing for humans. Unlike the other major genetic testing companies Ancestry and Family Tree DNA, 23andMe offers both health and ancestry results. The cost is $199.

As with Cody, I collected a saliva sample and dropped it in the mail. A few weeks later, I got an email saying my results were ready. I logged on to the website to see my ancestry composition distilled into a pie chart. The chart showed that my ancestors hailed from Korea, something I’d already been told. What I didn’t expect to see were the smaller slices indicating I had Japanese and Chinese ancestors scattered in. Seeing my genealogy for the first time was thrilling.

23andMe also scanned its database of others who had submitted their genetic material to the company for potential DNA matches. It identified over a hundred of my relatives, ranging from fourth to eighth cousins. 23andMe predicts that the average person has around half a million eighth cousins. The number gets exponentially larger as you go back generations. Some geneticists believe that all humans are at least 50th cousins with one another.

A messaging tool on the 23andMe website also allows you to connect with DNA relatives who’ve also taken the test. I eagerly exchanged messages with four of my distant cousins: the parent of a Chinese adoptee living in the Netherlands, the stepfather of a fifth cousin in the Philippines and a fellow Korean adoptee. Nobody could tell me more about my genealogy.

Only a fourth cousin named Henry who lives in California could shed light on a common ancestor who lived in Japan in the 1700s. He wrote in an email: “It would be an okay assumption that you may have genes to my father’s side, as his family was not in the bushi/samurai class, but comfortable merchants. Also, my patriarchal prefecture was sort of a ‘doorway’ to Japan.” Henry and I became Facebook friends, but I still have no tangible information about my ancestors.

Joy Lieberthal, a clinical social worker who specializes in issues related to adoption, said that for adoptees digging into their past, it’s important to look at the big picture. She explained that genetic testing kits really just give adoptees a history lesson in migration and land conflict over time, and that it’s important not to overstate the importance of the results. The bottom line: Just have fun with it.

In my health report, some of the inherited traits ranged from the frivolous (my sensitivity to bitter tastes) to T.M.I. (my type of earwax). It did pinpoint some of my physical attributes, like eye and hair color. It confirmed that I was lactose intolerant and predicted my athletic performance, based on my type of muscle fiber, compared to world class athletes. It suggested that, were I a runner, I would be better suited for sprinting than cross-country. It also confirmed that I lacked an enzyme to process and detoxify ethanol, making me sensitive to alcohol.

Over all, I was tested for 122 health risks and 53 inherited conditions. It showed I had a slightly higher than average risk for developing rheumatoid arthritis and ulcerative colitis and no inherited conditions. I had an elevated risk for developing restless leg syndrome. Was that why I felt that strange, jumpy sensation in my legs a few months ago? I made a note to mention this to my doctor at my next physical.

Through social media, I found other adoptees who had used DNA testing. An adoptee named Bee told me that her DNA test confirmed that she suffered from a rare and incurable genetic disease that affects her kidneys; with the results from her test, she was able to go to her doctor for an official diagnosis. She later learned that she had passed on the disease to her daughter, she told me.

Another adoptee named Janine, who was born in Korea and told by her adoptive parents that she was of mixed race, ordered a DNA kit so that she could learn about her biological father’s European lineage. Her ancestry results indicated she was 99.9 percent East Asian and only 0.1 percent European – hardly mixed race.

For me, DNA confirmed what I already knew: that the past is murky. After Henry’s email, follow-up messages from the relatives I was in contact with remained unanswered. It’s fun to think that I share some of my 20,000 genes with total strangers. But I think I’ll leave it at that. Piecing together a 20,000-piece jigsaw puzzle is a task too monumental to think about.

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Short Men, Overweight Women Face Lower Pay


Being tall is associated with higher income for men and being overweight is associated with lower income for women. A new study shows that height and weight may have a direct cause-and-effect relationship with pay.

The study used Mendelian randomization — a genetic technique that helps clarify the causal relationship between human characteristics — to show that genetically determined height and weight can directly affect worldly success.

British researchers studied 119,669 men and women who either had or did not have various genetic variants known to influence height and B.M.I.

The study, in BMJ, found that for each two and a half inches of genetically determined extra height, a man was 12 percent more likely to work in a high-status job and earned an average $1,611 more a year. In women, a 4.6-point increase in B.M.I. resulted in $4,200 less in annual income. These differences between the sexes strengthen the conclusion that the effect has a genetic basis, independent of environment.

That taller men and thinner women are more successful has been shown in several observational studies, and environmental factors are certainly involved.

“But your environment, your lifestyle, can’t change your genes,” said the senior author, Timothy M. Frayling, a professor of human genetics at the University of Exeter. “The data shows that there is a causal effect from being genetically a bit shorter or fatter that leads you to being worse off in life. Previously we didn’t know that.”