Posts Tagged ‘health’

By Yasemin Saplakoglu

Drinking a cup of tea or eating a handful of berries a day may help protect against heart disease, a new study suggests.

The research, presented November 10 at the American Heart Association’s Scientific Sessions annual meeting, found that daily consumption of small amounts of flavonoids — compounds found in berries, tea, chocolate, wine and many other fruits and plants — was associated with a lower risk of heart disease.

This association (which is not to be confused with a cause-and-effect finding) is not new; previous research has also found a link between flavonoids and heart disease risk. But the new study — one of the largest done to date — adds stronger evidence to the idea that flavonoids may protect the heart, said co-lead study author Nicola Bondonno, a postdoctoral researcher at the School of Biomedical Science at the University of Western Australia.

In the study, Bondonno and her team analyzed data from nearly 53,000 people who had participated in the long-running Danish Diet, Cancer and Health Study, which began in the 1990s. At the beginning of that study, participants filled out a questionnaire with information about what types of foods they ate and how often they ate them. The researchers then tracked the participants’ health for more than two decades.

After a 23-year follow-up period, around 12,000 of the participants had developed some sort of heart condition.

The researchers found that people who reported eating around 500 milligrams or more of flavonoids daily had a lower risk of developing ischemic heart disease (where the heart’s major blood vessels are narrowed, reducing blood flow to the heart), stroke and peripheral artery disease (where blood vessels in the body are narrowed, reducing blood flow throughout the body). This association was the greatest for the latter, the researchers found.

Bondonno noted that 500 mg of flavonoids is “very easy to eat in one day.” You would get that amount of flavonoids from “a cup of tea, a handful of blueberries, maybe some broccoli,” she said. They also found that, on average, it didn’t make too much of a difference how much more flavonoids healthy people consumed once they passed the 500 mg/day threshold.

The reason flavonoids could have a protective role against heart disease is because of their anti-inflammatory properties, Bondonno told Live Science. Inflammation is a risk factor for heart disease, she said.

The researchers noted that the association between flavonoids and reduced heart disease risk varied for different groups of people. The link between flavonoids and reduced risk of heart disease in smokers, for example, wasn’t observed at 500 mg of flavonoids a day; rather, smokers needed to eat more flavonoids for the link to be apparent. Similar results were seen in people who drank alcohol and in men. However, it was in these three groups that the researchers found that flavonoid intake was associated with the greatest reduction in risk.

In their analysis, Bondonno and her team made sure to take people’s whole diets into consideration, because people who tend to eat lots of fruits and vegetables (and in turn, consume a lot of flavonoids), tend to have better diets in general, eating more fiber and fish and less processed food, which are all “associated with heart disease,” Bondonno said. When they adjusted for these diets in their report, they found that the association between flavonoid intake and reduced heart disease risk was still there, but a bit weaker. In other words, flavonoids may not play as big a role in heart disease risk as a healthy diet would in general.

Further, the study was conducted only in Danish people, and though these results shouldn’t be extrapolated, “these kinds of associations have been seen in other populations,” Bondonno said.

The findings have not yet been published in a peer-reviewed journal.

https://www.livescience.com/64060-flavonoids-heart-health.html

Advertisements

Cannabis exposure during adolescence may interfere with the brain’s maturation, at least in rats, according to research presented at the Society for Neuroscience meeting in San Diego this week. Scientists find that a synthetic cannabinoid can throw dopamine signaling out of whack and alter the development of the prefrontal cortex.

As states continue to legalize both medical and recreational marijuana, more and more teens are using the drug. According to the Scripps Research Institute’s Michael Taffe, who moderated a press conference today (November 6), 35 percent of high school seniors in the US have smoked pot in the past year, and 14 percent say they have smoked it every day for a month at some point in their lives.

This has cannabis researchers interested in how marijuana use affects teens’ developing brains. In one study described during the event with reporters, José Fuentealba Evans of the Pontificia Universidad Católica de Chile and his colleagues injected adolescent rats with a synthetic cannabinoid and found that such exposure had a “huge increase” in dopaminergic activity in the nigrostriatal pathway of the striatum compared with rats that received a placebo, he explains. This excitatory circuit plays a role in reward processing and addiction, for example, and such changes may encourage risky behavior.

In another study presented today, Jamie Roitman’s group at the University of Illinois at Chicago found that rats given this same drug had fewer inhibitory neurons in regions of the prefrontal cortex, as well as reduced levels of the perineuronal nets that help stabilize those circuits, compared with control animals. This part of the brain, which matures late in development as excitatory synapses are pruned and inhibitory synapses proliferate, controls the highly active motivational circuits, such as the nigrostriatal pathway, that mature earlier, Roitman explains.

“Adolescence is much more dopamine controlled, as you’re waiting for the prefrontal cortex to come online and execute planning and control over behavior,” she tells The Scientist. Thus, adolescents who use cannabis may be “at risk of changing the structure of the brain while it’s maturing.”

https://www.the-scientist.com/news-opinion/cannabinoid-exposure-during-adolescence-disrupts-neural-regulation-65047

181307_web-1

Whiile human genetic mutations are involved in a small number of Parkinson’s disease (PD) cases, the vast majority of cases are of unknown environmental causes, prompting enormous interest in identifying environmental risk factors involved. The link between Helicobacter pylori (H. pylori) and gastric ulcers has been known for several decades, but new evidence suggests that this harmful bacterium may play a role in PD as well. A new review in the Journal of Parkinson’s Disease summarizes the current literature regarding the link between H. pylori and PD and explores the possible mechanisms behind the association.

In a comprehensive review of prior studies, investigators uncovered four key findings:

People with PD are 1.5-3-fold more likely to be infected with H. pylori than people without PD.
H. pylori-infected PD patients display worse motor functions than H. pylori-negative PD patients.
Eradication of H. pylori improved motor function in PD patients over PD patients whose H. pylori was not eradicated.
Eradication of H. pylori improved levodopa absorption in PD patients compared to PD patients whose H. pylori was not eradicated.
“This is an in-depth and comprehensive review that summarizes all the major papers in the medical literature on Parkinson’s disease and H. pylori, the common stomach bacterium that causes gastritis, ulcers and stomach cancer,” explained lead investigator David J. McGee, PhD, Associate Professor, Department of Microbiology and Immunology, LSU Health Sciences Center-Shreveport, Shreveport, LA, USA. “Our conclusion is that there is a strong enough link between the H. pylori and Parkinson’s disease that additional studies are warranted to determine the possible causal relationship.”

Investigators also analyzed existing studies to try and find possible testable pathways between the bacterial infection and Parkinson’s to lay the groundwork for future research. They found four main possible explanations for the association:

Bacterial toxins produced by H. pylori may damage neurons.

The infection triggers a massive inflammatory response that causes damage to the brain.

H. pylori may disrupt the normal gut microbial flora.

The bacteria might interfere with the absorption properties of levodopa, the medication commonly used to treat the symptoms of Parkinson’s disease.

The onset of PD is often preceded by gastrointestinal dysfunction, suggesting that the condition might originate in the gut and spread to the brain along the brain-gut axis. In the review, investigators note that this has been documented in rats.

Screening PD patients for the presence of H. pylori and subsequent treatment if positive with anti-H. pylori triple drug therapy, may contribute to improved levodopa absorption and ultimately improvement of PD symptoms, potentially leading to a longer life span in patients with PD.

“Evidence for a strong association among H. pylori chronic infection, peptic ulceration and exacerbation of PD symptoms is accumulating,” concluded Dr. McGee.

“However, the hypotheses that H. pylori infection is a predisposing factor, disease progression modifier, or even a direct cause of PD remain largely unexplored. This gut pathology may be multifactorial, involving H. pylori, intestinal microflora, inflammation, misfolding of alpha-synuclein in the gut and brain, cholesterol and other metabolites, and potential neurotoxins from bacteria or dietary sources. Eradication of H. pylori or return of the gut microflora to the proper balance in PD patients may ameliorate gut symptoms, L-dopa malabsorption, and motor dysfunction.”

https://scienmag.com/eradicating-helicobacter-pylori-infections-may-be-a-key-treatment-for-parkinsons-disease/

mice-x

by SUKANYA CHARUCHANDRA

The protein Bmal1, which helps regulate the body’s internal clock, is found in especially high levels in the brain and in skeletal muscles. Mice completely deficient in Bmal1 were known to suffer from sleep impairments, but the specifics at play weren’t clear. At the University of California, Los Angeles, Ketema Paul and colleagues looked to these mice for clues about the role Bmal1 plays in sleep regulation.

MUSCLE PLAY
When Paul’s team restored levels of the Bmal1 protein in the mice’s brains, their ability to rebound from a night of bad sleep remained poor. However, turning on production in skeletal muscles alone enabled mice to sleep longer and more deeply to recover after sleep loss.

SWEET DREAMS
For decades, scientists have thought sleep was controlled purely by the brain. But the new study indicates the ability to catch up on one’s sleep after a bout of sleeplessness is locked away in skeletal muscles, not the brain—at least for mice. “I think it’s a real paradigm shift for how we think about sleep,” says John Hogenesch, a chronobiologist at Cincinnati Children’s Hospital Medical Center who discovered the Bmal1 gene but was not involved in this study.

TARGET LOCKED
Paul’s group also found that having too much of the Bmal1 protein in their muscles not only made mice vigilant but also invulnerable to the effects of sleep loss, so that they remained alert even when sleep-deprived and slept fewer hours to regain lost sleep. “To me, that presents a potential target where you could treat sleep disorders,” says Paul, noting that an inability to recover from sleep loss can make us more susceptible to diseases.

The paper
J.C. Ehlen et al., “Bmal1 function in skeletal muscle regulates sleep,” eLife, 6:e26557, 2017.

https://www.the-scientist.com/the-literature/muscles-hold-a-key-to-sleep-recovery-64685?utm_campaign=TS_DAILY%20NEWSLETTER_2018&utm_source=hs_email&utm_medium=email&utm_content=66141129&_hsenc=p2ANqtz–EaFM3BB6i_l04LL2zbvjlEHCWVwrSrks2D9Aksml-wGa9f88gfOwPhtiPCXEMJRqzu6WG53_vzEvHht0oAGylLgMANQ&_hsmi=66141129

germ_custom-ce83850a07c80ed6e717ea56370b3c5140eb2f3f-s800-c85

by BRET STETKA

Dr. Leslie Norins is willing to hand over $1 million of his own money to anyone who can clarify something: Is Alzheimer’s disease, the most common form of dementia worldwide, caused by a germ?

By “germ” he means microbes like bacteria, viruses, fungi and parasites. In other words, Norins, a physician turned publisher, wants to know if Alzheimer’s is infectious.

It’s an idea that just a few years ago would’ve seemed to many an easy way to drain your research budget on bunk science. Money has poured into Alzheimer’s research for years, but until very recently not much of it went toward investigating infection in causing dementia.

But this “germ theory” of Alzheimer’s, as Norins calls it, has been fermenting in the literature for decades. Even early 20th century Czech physician Oskar Fischer — who, along with his German contemporary Dr. Alois Alzheimer, was integral in first describing the condition — noted a possible connection between the newly identified dementia and tuberculosis.

If the germ theory gets traction, even in some Alzheimer’s patients, it could trigger a seismic shift in how doctors understand and treat the disease.

For instance, would we see a day when dementia is prevented with a vaccine, or treated with antibiotics and antiviral medications? Norins thinks it’s worth looking into.

Norins received his medical degree from Duke in the early 1960s, and after a stint at the Centers for Disease Control and Prevention he fell into a lucrative career in medical publishing. He eventually settled in an admittedly aged community in Naples, Fla., where he took an interest in dementia and began reading up on the condition.

After scouring the medical literature he noticed a pattern.

“It appeared that many of the reported characteristics of Alzheimer’s disease were compatible with an infectious process,” Norins tells NPR. “I thought for sure this must have already been investigated, because millions and millions of dollars have been spent on Alzheimer’s research.”

But aside from scattered interest through the decades, this wasn’t the case.

In 2017, Norins launched Alzheimer’s Germ Quest Inc., a public benefit corporation he hopes will drive interest into the germ theory of Alzheimer’s, and through which his prize will be distributed. A white paper he penned for the site reads: “From a two-year review of the scientific literature, I believe it’s now clear that just one germ — identity not yet specified, and possibly not yet discovered — causes most AD. I’m calling it the ‘Alzheimer’s Germ.’ ”

Norins is quick to cite sources and studies supporting his claim, among them a 2010 study published in the Journal of Neurosurgery showing that neurosurgeons die from Alzheimer’s at a nearly 2 1/2 times higher rate than they do from other disorders.

Another study from that same year, published in The Journal of the American Geriatric Society, found that people whose spouses have dementia are at a 1.6 times greater risk for the condition themselves.

Contagion does come to mind. And Norins isn’t alone in his thinking.

In 2016, 32 researchers from universities around the world signed an editorial in the Journal of Alzheimer’s Disease calling for “further research on the role of infectious agents in [Alzheimer’s] causation.” Based on much of the same evidence Norins encountered, the authors concluded that clinical trials with antimicrobial drugs in Alzheimer’s are now justified.

NPR reported on an intriguing study published in Neuron in June that suggested that viral infection can influence the progression of Alzheimer’s. Led by Mount Sinai genetics professor Joel Dudley, the work was intended to compare the genomes of healthy brain tissue with that affected by dementia.

But something kept getting in the way: herpes.

Dudley’s team noticed an unexpectedly high level of viral DNA from two human herpes viruses, HHV-6 and HHV-7. The viruses are common and cause a rash called roseola in young children (not the sexually transmitted disease caused by other strains).

Some viruses have the ability to lie dormant in our neurons for decades by incorporating their genomes into our own. The classic example is chickenpox: A childhood viral infection resolves and lurks silently, returning years later as shingles, an excruciating rash. Like it or not, nearly all of us are chimeras with viral DNA speckling our genomes.

But having the herpes viruses alone doesn’t mean inevitable brain decline. After all, up to 75 percent of us may harbor HHV-6 .

But Dudley also noticed that herpes appeared to interact with human genes known to increase Alzheimer’s risk. Perhaps, he says, there is some toxic combination of genetic and infectious influence that results in the disease; a combination that sparks what some feel is the main contributor to the disease, an overactive immune system.

The hallmark pathology of Alzheimer’s is accumulation of a protein called amyloid in the brain. Many researchers have assumed these aggregates, or plaques, are simply a byproduct of some other process at the core of the disease. Other scientists posit that the protein itself contributes to the condition in some way.

The theory that amyloid is the root cause of Alzheimer’s is losing steam. But the protein may still contribute to the disease, even if it winds up being deemed infectious.

Work by Harvard neuroscientist Rudolph Tanzi suggests it might be a bit of both. Along with colleague Robert Moir, Tanzi has shown that amyloid is lethal to viruses and bacteria in the test tube, and also in mice. He now believes the protein is part of our ancient immune system that like antibodies, ramps up its activity to help fend off unwanted bugs.

So does that mean that the microbe is the cause of Alzheimer’s, and amyloid a harmless reaction to it? According to Tanzi it’s not that simple.

Tanzi believes that in many cases of Alzheimer’s, microbes are probably the initial seed that sets off a toxic tumble of molecular dominoes. Early in the disease amyloid protein builds up to fight infection, yet too much of the protein begins to impair function of neurons in the brain. The excess amyloid then causes another protein, called tau, to form tangles, which further harm brain cells.

But as Tanzi explains, the ultimate neurological insult in Alzheimer’s is the body’s reaction to this neurotoxic mess. All the excess protein revs up the immune system, causing inflammation — and it’s this inflammation that does the most damage to the Alzheimer’s-afflicted brain.

So what does this say about the future of treatment? Possibly a lot. Tanzi envisions a day when people are screened at, say, 50 years old. “If their brains are riddled with too much amyloid,” he says, “we knock it down a bit with antiviral medications. It’s just like how you are prescribed preventative drugs if your cholesterol is too high.”

Tanzi feels that microbes are just one possible seed for the complex pathology behind Alzheimer’s. Genetics may also play a role, as certain genes produce a type of amyloid more prone to clumping up. He also feels environmental factors like pollution might contribute.

Dr. James Burke, professor of medicine and psychiatry at Duke University’s Alzheimer’s Disease Research Center, isn’t willing to abandon the amyloid theory altogether, but agrees it’s time for the field to move on. “There may be many roads to developing Alzheimer’s disease and it would be shortsighted to focus just on amyloid and tau,” he says. “A million-dollar prize is attention- getting, but the reward for identifying a treatable target to delay or prevent Alzheimer’s disease is invaluable.”

Any treatment that disrupts the cascade leading to amyloid, tau and inflammation could theoretically benefit an at-risk brain. The vast majority of Alzheimer’s treatment trials have failed, including many targeting amyloid. But it could be that the patients included were too far along in their disease to reap any therapeutic benefit.

If a microbe is responsible for all or some cases of Alzheimer’s, perhaps future treatments or preventive approaches will prevent toxin protein buildup in the first place. Both Tanzi and Norins believe Alzheimer’s vaccines against viruses like herpes might one day become common practice.

In July of this year, in collaboration with Norins, the Infectious Diseases Society of America announced that they plan to offer two $50,000 grants supporting research into a microbial association with Alzheimer’s. According to Norins, this is the first acknowledgement by a leading infectious disease group that Alzheimer’s may be microbial in nature – or at least that it’s worth exploring.

“The important thing is not the amount of the money, which is a pittance compared with the $2 billion NIH spends on amyloid and tau research,” says Norins, “but rather the respectability and more mainstream status the grants confer on investigating of the infectious possibility. Remember when we thought ulcers were caused by stress?”

Ulcers, we now know, are caused by a germ.

https://www.npr.org/sections/health-shots/2018/09/09/645629133/infectious-theory-of-alzheimers-disease-draws-fresh-interest?ft=nprml&f=1001

The discovery sheds new light on the origins of this most common cause of dementia, a hallmark of which is the buildup of tangled tau protein filaments in the brain.

The finding could also lead to new treatments for Alzheimer’s and other diseases that progressively destroy brain tissue, conclude the researchers in a paper about their work that now features in the journal Neuron.

Scientists from Massachusetts General Hospital (MGH) in Charlestown and the Johns Hopkins School of Medicine in Baltimore, MD, led the study, which set out to investigate how tau protein might contribute to brain cell damage.

Alzheimer’s disease does not go away and gets worse over time. It is the sixth most common cause of death in adults in the United States, where an estimated 5.7 million people have the disease.

Exact causes of Alzheimer’s still unknown

Exactly what causes Alzheimer’s and other forms of dementia is still a mystery to science. Evidence suggests that a combination of environment, genes, and lifestyle is involved, with different factors having different amounts of influence in different people.

Most cases of Alzheimer’s do not show symptoms until people are in their 60s and older. The risk of getting the disease rises rapidly with age after this.

Brain studies of people with the disease — together with postmortem analyses of brain tissue — have revealed much about how Alzheimer’s changes and harms the brain.

“Age-related changes” include: inflammation; shrinkage in some brain regions; creation of unstable, short-lived molecules known as free radicals; and disruption of cellular energy production.

The brain of a person with Alzheimer’s disease also has two distinguishing features: plaques of amyloid protein that form between cells, and tangles of tau protein that form inside cells. The recent study concerns the latter.

Changes to tau behavior

Brain cells, or neurons, have internal structures known as microtubules that support the cell and its function. They are highly active cell components that help carry substances from the body of the cell out to the parts that connect it to other cells.

In healthy brain cells, tau protein normally “binds to and stabilizes” the microtubules. Tau behaves differently, however, in Alzheimer’s disease.

Changes in brain chemistry make tau protein molecules come away from the microtubules and stick to each other instead.

Eventually, the detached tau molecules form long filaments, or neurofibrillary tangles, that disrupt the brain cell’s ability to communicate with other cells.

The new study introduces the possibility that, in Alzheimer’s disease, tau disrupts yet another mechanism that involves communication between the nucleus of the brain cell and its body.

Communication with cell nucleus

The cell nucleus communicates with the rest of the cell using structures called nuclear pores, which comprise more than 400 different proteins and control the movement of molecules.

Studies on the causes of amyotrophic lateral sclerosis, frontotemporal, and other types of dementia have suggested that flaws in these nuclear pores are involved somehow.

The recent study reveals that animal and human cells with Alzheimer’s disease have faulty nuclear pores, and that the fault is linked to tau accumulation in the brain cell.

“Under disease conditions,” explains co-senior study author Bradley T. Hyman, the director of the Alzheimer’s Unit at MGH, “it appears that tau interacts with the nuclear pore and changes its properties.”

He and his colleagues discovered that the presence of tau disrupts the orderly structure of nuclear pores containing the major structural protein Nup98. In Alzheimer’s disease cells, there were fewer of these pores and those that were there tended to be stuck to each other.

‘Mislocalized’ Nup98
They also observed another curious change involving Nup98 inside Alzheimer’s disease brain cells. In cells with aggregated tau, the Nup98 was “mislocalized” instead of staying in the nuclear pore.

They revealed that this feature was more exaggerated in brain tissue of people who had died with more extreme forms of Alzheimer’s disease.

Finally, when they added human tau to living cultures of rodent brain cells, the researchers found that it caused mislocalization of Nup98 in the cell body and disrupted the transport of molecules into the nucleus.

This was evidence of a “functional link” between the presence of tau protein and damage to the nuclear transport mechanism.

The authors note, however, that it is not clear whether the Nup98-tau interaction uncovered in the study just occurs because of disease or whether it is a normal mechanism that behaves in an extreme fashion under disease conditions.

They conclude:

“Taken together, our data provide an unconventional mechanism for tau-induced neurodegeneration.”

https://www.medicalnewstoday.com/articles/322991.php

GWAS_ADN1.0

In the United States, around 735,000 people each year have a heart attack. In all, heart disease (and its complications, including heart attacks) kills 610,000 a year here, making it the leading cause of death in America and worldwide.

Preventing heart disease is a huge public health challenge. And right now doctors have good, but limited, options for finding out who is at greatest risk for it.

Doctors know that about half the risk for heart disease comes from lifestyle choices: how much, and what, a person is eating, how much alcohol they drink, if they smoke.

The other half is related to genetics, and it’s much harder to assess. You can ask a person about their family history of heart disease and can check for high blood pressure and obesity, which are also related to genetics. But up until the recent explosion in genetic science, it was hard to probe the genes themselves.

Last week, in the journal Nature Genetics, researchers at Harvard University and the Broad Institute published evidence that they can check out 6 million spots in a person’s genome to assess their risk for developing coronary artery disease, when the main blood vessel supplying the heart with oxygen gets clogged with plaque. It’s a precursor to a heart attack, when a clot cuts off blood flow to the heart, starving it of oxygen.

In the study, people who carried the greatest number of genetic variants suggestive of heart attack risk were three or more times likely to develop coronary artery disease than controls. The researchers argue that with this test, about one in 12 people could be identified as having a higher risk of heart attack based on their genetics alone.

“If you told me there was a genetic score that could identify 8 percent of the population with more than a threefold risk, I’d say, that’s amazing,” Robert Yeh, a cardiologist at the Smith Center for Outcomes Research in Cardiology, who was not involved in the study, says. Currently, the best commonly available genetic test for heart disease risk — which looks for a single gene linked to high cholesterol — can only detect increased risk in 0.4 percent of people.

“The big takeaway is that we can now capture the inherited component to heart attack risk with a single number,” Sekar Kathiresan, the Massachusetts General Hospital cardiologist and geneticist who led the study, says. With this new tool, Kathiresan hopes doctors could put those people at higher risk on cholesterol-lowering medications (statins) at an earlier age, or more easily persuade them to make lifestyle changes to lower their risk.

The new tool here is called a polygenic risk score, which you can think of as a tally of the tiny changes in your genome that are correlated with risk of developing a disease.

In the coming years, you’re going to hear a lot more about them. These scores, while increasingly helpful in some areas of medicine, come with a lot of caveats. Indeed, when you dig a bit deeper into this latest Nature Genetics paper, you find there’s a lot more work to do to validate polygenic risk scores for heart disease, so they will be useful and relevant to people around the globe. For one: This study was exclusively conducted with subjects in the UK of white European background. The predictions derived from this group do not necessarily transfer over to another. For this and other reasons, scientists skeptical of polygenic risk scores say they are not yet ready for the clinic — and wonder if they will ever be.

At the same time, it seems likely these polygenic risk scores are going to change the way we think about our health and our medical decision-making.

What’s a polygenic risk score?
Over the past decade, medical researchers have realized that our risk for many common conditions like heart disease and diabetes are not influenced by just one gene, or even a small handful of them. Instead, studies analyzing huge numbers of sequenced human genomes have found that there are hundreds of genes that work in constellation influencing our risk for diseases.

DNA is the recipe for our biology. But it turns out that recipe looks something like an M.C. Escher drawing, with a huge number of genes influencing life outcomes in hard-to-understand, hard-to-follow, interconnected ways.

That is, there can be hundreds of interrelated spots in the genome that are correlated with a person’s risk for heart disease, or raising or lowering their height by a millimeter. Scientists are getting better at identifying these spots in the genome that confer risk and are now trying to figure out if tallying up these genetic changes — in what’s known as a “polygenic risk score” — is useful in trying to predict, and prevent, disease. (They are also calculating them for behavioral traits like educational attainment.)

In developing polygenic risk scores, in many cases, genetics researchers often don’t know what the underlying genes do. All they know is that these genes are correlated with — which does not mean cause — the disease. “It’s pretty mindless,” says Cecile Janssens, an epidemiologist at Emory University who is critical of the hype of polygenic risk scores.

Proponents of polygenic scoring, though, argue that you don’t need to know what the genes are doing to make predictions off them.

“It’s all about getting a predictor and then repeating it in other groups,” Kathiresan says. “At the end of the day, I could just call it a magic number generator. It doesn’t exactly matter how I’m getting there, as long as it works in other groups equally well.”

That’s what happened in this latest paper. A polygenic risk score derived from huge genome-wide association studies predicted heart attack risk in nearly 300,000 people in the UK. (Read more about how scientists come up with polygenic risk scores here.)

How good is the prediction?
Because each change in the genome — called single nucleotide polymorphisms, or SNPs (pronounced “snip”) — confers such a tiny change in risk, adding more and more of them to the risk score yields diminishing returns. “We see this trend already for years — every new SNP that we discover has a smaller effect than we knew already,” Janssens, says.

In the recent Nature Genetics study, she points out, when the researchers increased the number of SNPs in their risk model from 74 to 6 million, the predictive power of the test only increased by a smidgen. Most of those SNPs have a predictive power of approximately zero.

Here’s a chart showing where the polygenic risk score for coronary artery disease matters most. Polygenic scores, like so many human traits, are normally distributed, meaning they follow the pattern of the bell curve. But a person’s risk for coronary artery disease really only starts to increase if they have the very highest number of SNPs that are correlated with heart disease risk. The top 8 percent of the participants had a three times greater risk of heart disease. The top 0.5 percent had five times the risk.

There are many caveats to this risk prediction, which the authors of the study acknowledge. One is that it’s currently unclear if predicting heart attack risk in this manner provides an additional benefit to the risk models derived from asking people simple questions about their lifestyle and family history. The researchers suspect it does, but they didn’t set up their study to test this question.

Another is that this risk model was developed and tested solely on people who had donated their medical and genetic information to the UK Biobank, which contains only genetic data of people of white, European ancestry. The predictive power of these tests is expected to diminish in people of African ancestry, Asian ancestry, and so on. Genetics researchers will need to repeat polygenic risk studies with data from these populations if these predictions are truly going to be useful and equitable.

And yet one more: We shouldn’t take it for granted that intervening with early medication or lifestyle changes for the people at highest risk will make a difference in lowering their risk. Other studies have found that people with higher genetic risk scores for atherosclerosis tend to receive a stronger benefit from statins. But the question needs further testing.

All that said, Yeh, the research cardiologist, says there’s still a lot of optimism around these scores. Current risk factors for heart disease, like high blood pressure or family history, don’t always help single out who truly is most at risk.

“The majority of being who develop coronary artery disease are not people who have a multitude of cardiac risk factors,” Yeh says. “About half of people have just one risk factor, high blood pressure alone. People like that, although they only have one cardiac risk factor, sometimes none, they wouldn’t think of themselves of [having] a very high elevated risk for coronary artery disease.”

A genetic risk factor could help narrow it down.

We’re going to start seeing more and more polygenic tests for disease risk
Polygenic risk scores, says Eric Topol, a cardiologist and geneticist with Scripps Research, “are going to take hold in common medical practice. It’s a matter of when, not if.”

And they’ll be used for conditions outside of heart disease. Indeed, in the latest Nature Genetics study, the researchers also calculated risk scores for diabetes, atrial fibrillation (irregular heart rhythm), inflammatory bowel disease, and breast cancer. The genetic tests for these conditions found fewer people at elevated risk than the tests for heart disease. And not every test will be equally predictive.

Kathiresan points out that while only 8 percent of the study participants were singled out for elevated risk for coronary artery disease, about 20 percent of all the participants were flagged as having elevated risk for at least one of the diseases listed above.

And while these scores are now being generated for all kinds of health and behavioral issues, medicine isn’t really ready to implement them. Huge questions remain. For instance, while it’s possible to do a genetic risk assessment of an infant, or even an embryo, does it make sense or is it even ethical for new parents to learn their embryos or newborns are at a threefold risk for heart disease?

Doctors will also have to think long and hard about how they discuss these kinds of risks with their patients. Scoring in the 70th percentile of risk for coronary artery disease may sound scary, but it won’t increase a person’s chances of getting that disease by all that much.

There are also likely to be unintended consequences of giving patients a new health metric to fear. Consider what happened with cholesterol, a risk factor for heart disease that people began being commonly tested for in the 1980s. Fear of cholesterol came to inspire low-fat food trends. Those dietary trends made food companies money, but they didn’t necessarily make people healthier, especially as many of the foods marketed as low-fat were still loaded with sugar.

What happens when some huckster starts selling vitamins to complement a polygenic risk score, or some other forms of woo? (Currently, you can buy a customized diet guide based on a sequencing of your DNA.) There’s a lot of education that needs to happen here to prevent genetic risk prediction from becoming genetic astrology.

For now, aside from a polygenic risk score for breast cancer, these tests don’t yet exist in the clinic. But they’re going to get easier and easier to discover on your own. If you have your genetics data from a commercial company like 23andMe, you can upload it to a number of sites on the internet to see your risk scores for a slew of traits and diseases. Kathiresan’s team is hoping to build a free tool for people to assess their coronary artery disease risk in this manner.

Here’s a reasonable fear: It’s going to be hard for consumers, without much input from doctors, to know when the risk scores matter and when they do not. Heck, you can currently take a genetics test for intelligence that really won’t tell you anything valuable. It’s possible to develop polygenic risk score for loneliness, baldness, marital status, or really any human trait that is even vaguely influenced by genes. It takes more information — like odds ratios — to know whether those scores really matter in your life.

It will also be hard to know what to do to diminish risk. A high polygenic score for breast cancer might mean a woman wants to make more frequent mammogram appointments, Janssens says. But the current recommendations for people at higher risk of heart disease are things everyone should be doing: living a healthy lifestyle free of tobacco.

“I actually think there’s going to be a whole [medical] field that emerges, kind of like radiology emerged in 1900 with the invention of X-rays,” Kathiresan says, “where [doctors] are basically interpreting that genetic information for medical risk.”

That field needs to start up soon, because there’s a lot more coming.

https://www.vox.com/science-and-health/2018/8/24/17759772/genetics-polygenic-risk-heart-disease-nature