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Study finds rare, but influential, genetic changes related to height

In the largest, deepest search to date, the international Genetic Investigation of Anthropometric Traits (GIANT) Consortium has uncovered 83 new DNA changes that affect human height. These changes are uncommon or rare, but they have potent effects, with some of them adjusting height by more than 2 cm (almost 8/10 of an inch).

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In the largest, deepest search to date, the international Genetic Investigation of Anthropometric Traits (GIANT) Consortium has uncovered 83 new DNA changes that affect human height. These changes are uncommon or rare, but they have potent effects, with some of them adjusting height by more than 2 cm (almost 8/10 of an inch). The 700,000-plus-person study also found several genes pointing to previously unknown biological pathways involved in skeletal growth. Findings were published online by Nature.

GIANT

“While our last study identified common height-related changes in the genome, this time we went for low-frequency and rare changes that directly alter proteins and tend to have stronger effects,” says Joel Hirschhorn, MD, PhD, of Boston Children’s Hospital and the Broad Institute of MIT and Harvard, chair of the GIANT Consortium and co-senior investigator on the study together with researchers at the Montreal Heart Institute, Queen Mary University, the University of Exeter, UK, and nearly 280 other research groups. “To identify these protein-altering changes, some of them very uncommon, required tremendous statistical power, which we achieved thanks to a strong international collaboration.”

Applying a new technology

In 2014, GIANT, studying roughly 250,000 people, brought the total number of known genetic variants to nearly 700 — in more than 400 spots in the genome. This effort involved a powerful method called genome-wide association study (GWAS), which rapidly scans across the genomes of large populations for markers that track with a particular trait. GWAS are good at finding common genetic variants, but nearly all of the identified variants alter height by less than 1 mm (less than 1/20 of an inch). GWAS studies are not as good at capturing uncommon genetic variants, which can have larger effects. Finally, the common variants that track with traits tend to lie mostly outside the protein-coding parts of genes, making it harder to figure out which genes they affect.

So in the new study, the GIANT investigators used a different technology: the ExomeChip, which tested for a catalogue of nearly 200,000 known variants that are less common and that alter the function of protein-coding genes. These variants point more directly to genes and can be used as a shortcut to figuring out which genes are important for a specific disease or trait. Most had not been assessed in prior genetic studies of height.

Using ExomeChip data from a total of 711,428 adults (an initial 460,000 people and about 250,000 more to validate the findings), the investigators identified 83 uncommon variants associated with adult height: 51 “low-frequency” variants (found in less than 5 percent of people) and 32 rare variants (found in less than 0.5 percent).

With these new findings, 27.4 percent of the heritability of height is now accounted for (up from 20 percent in earlier studies), with most heritability still explained by common variants.

Twenty-four of the newly discovered variants affect height by more than 1 cm (4/10 of an inch), larger effects than typically seen with common variants. “This finding matches a pattern seen in other genetic studies, where the more potent variants are rarer in the population,” says Hirschhorn, who is also an endocrinologist at Boston Children’s and a professor of pediatrics and genetics at Harvard Medical School.

Rare but potent clues to new biology

These rare variants not only had large effects but also pointed to dozens of genes as important for skeletal growth. Some of these genes were already known, but many (including SUSD5, GLT8D2, LOXL4, FIBIN, and SFRP4) have not previously been connected with skeletal growth.

One gene of particular interest, STC2, had two different DNA changes that both had larger effects on height. Though the variants are quite rare (frequency of 0.1 percent), people with either of these changes were 1-2 cm taller than non-carriers. Further investigations by co-authors Troels R. Kjaer and Claus Oxvig of Aarhus University (Denmark) suggested that the variants influence height by affecting the availability of growth factors in the blood. “The STC2 protein serves as a brake on human height, validating it as a potential drug target for short stature,” says Hirschhorn.

Height: A window into complex genetics

Why study height? Height is the “poster child” of complex genetic traits, meaning it is influenced by multiple genetic variants working together. It’s easy to measure, so makes a relatively simple model for understanding traits produced by not one gene, but many.

“Mastering the complex genetics of height may give us a blueprint for studying multifactorial disorders that have eluded our complete understanding, such as diabetes and heart disease,” says Hirschhorn.  “This study has shown that rare protein-altering variants can be helpful at finding some of the important genes, but also that even larger sample sizes will be needed to completely understand the genetic and biologic basis of human growth and other multifactorial diseases.”

Indeed, the GIANT consortium is already embarking on a GWAS of height with more than 2 million people, and other studies involving sequencing data are underway. “We predict that these more comprehensive studies will continue to enhance our understanding of human growth and how best to attain the biological insights that will inform treatments for common diseases,” says Hirschhorn.

In addition to Hirschhorn, the study’s co-senior authors include Timothy Frayling of the University of Exeter, Panos Deloukas of the Queen Mary University of London and Guillaume Lettre of the University of Montreal. Co-first authors were Eirini Marouli of Queen Mary University; Mariaelisa Graff of the University of North Carolina, Chapel Hill; Carolina Medina-Gomez of Erasmus Medical Center (Rotterdam, Netherlands); Ken Sin Lo of the Montreal Heart Institute; Andrew R Wood of the University of Exeter (U.K.), Troels R. Kjaer of Aarhus University (Denmark), Rebecca S. Fine of the Broad Institute, Boston Children’s Hospital and Harvard Medical School; and Yingchang Lu of Vanderbilt University (Nashville, TN) and the Icahn School of Medicine at Mount Sinai (New York). The study’s numerous funding sources include the National Institutes of Health, the Wellcome Trust, MRC, the European Research Council, the European Union, the Canadian Government, the Canadian Institutes of Health Research, the Danish Council, Novo Nordisk and the Lundbeck Foundation.

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‘Drunk riding’ behind almost half of fatal electric scooter crashes

Tatal crashes occur mainly in the evenings or through the night, and in all cases, no helmet has been worn.

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In almost half of all fatal electric scooter crashes in Sweden, the rider has been under the influence of alcohol. These fatal crashes occur mainly in the evenings or through the night, and in all cases, no helmet has been worn. This is shown by a new study from Chalmers University of Technology, in Sweden, and the Swedish Transport Administration. The study also states that most fatal crashes occur with private electric scooters, rather than rentals.

The researchers have analysed all fatal crashes involving electric scooters, electric bicycles and conventional bicycles in Sweden between 2016 and 2024.

Alcohol is often a factor in fatal crashes occurring with all three of these vehicle types – but the figures for electric scooters stand out. Of the fatal e-scooter crashes, 44 per cent of the riders were under the influence of alcohol, compared to 27 per cent among e-bike riders and 13 per cent among cyclists.

More specifically the levels of alcohol in the blood have been shown to be high across all three groups. Of the e-scooter riders that were under the influence of alcohol, the median blood alcohol content was 1.8 per mille. This can be compared to the legal limit of alcohol content in the blood for driving a car in Sweden, which is 0.2 per mille, above which it is considered drunk driving, and 1.0 per mille in the blood which is considered aggravated drunk driving.

“Alcohol intoxication is a common issue among all road users, but it appears to be particularly severe among riders of electric scooters. Not only were many fatally injured e‑scooter riders intoxicated, but their levels of intoxication were also extremely high,” says Marco Dozza, Professor of Active Safety and Road User Behaviour at Chalmers University of Technology, and senior researcher in the study.

Lack of helmets worn in those killed

The study also showed that helmet use in fatal crashes was very low. Of those fatally injured riding an e-scooter, none were wearing a helmet. And for those killed riding an e-bike or a bicycle, only about 25 per cent were wearing a helmet.

Head injuries were the most common cause of death in all groups.

“The numbers speak for themselves. Since the head is the area of the body that is most affected by a fatal injury and almost no one wears a helmet, we have a clear opportunity to save lives. A helmet is not a guarantee but improves the chances dramatically, so we should do everything we can to encourage helmet use,” says Rahul Rajendra Pai, doctoral student at Chalmers and first author of the study.

“I think many people don’t understand the danger of using an electric scooter under the influence of alcohol, and think that the vehicle doesn’t go that fast,” says Marco Dozza. “But it is enough hitting a stone on the road or a small hole in the ground to lose balance, especially when intoxicated, because alcohol slows down cognition and reactions. If you don’t wear a helmet, it may end up even worse”.

Different crash patterns for different vehicles

The study included 204 deaths, and the researchers saw clear differences between the three vehicle types in terms of rider and crash patterns.

In fatal crashes involving ordinary bicycles, the median age of the cyclist was 71 years old. The crashes often occurred on weekdays and usually involved collisions with motor vehicles.

Fatal e-scooter crashes looked different. The riders had a median age of 47.5 years old, and most of the crashes were single vehicle crashes that occurred at weekends, evenings and nights.

According to the researchers, the results indicate the need for measures and regulations to be adapted to the different types of vehicles.

“The typical fatal bicycle crash, with an elderly cyclist being hit by a motor vehicle in daylight, may require completely different countermeasures than the typical fatal electric scooter crash, where a younger rider crashes alone at night while intoxicated,” says Marco Dozza.

Fatal crashes most common with private electric scooters

Almost nine out of ten alcohol-related e-scooter deaths occurred with privately owned vehicles. Public debate and regulations have largely focused on rented electric scooters, and operators have introduced measures such as speed limits and night restrictions. However, these measures do not affect privately owned electric scooters.

According to the researchers, rules and measures can to some extent counteract crashes with electric scooters. Marco Dozza, for example, is leading an ongoing study on how today’s sensor technology in rented electric scooters can make it possible to detect impaired riding ability in real time.

“If a vehicle can identify that its rider is not in control, it is possible to take various measures before a crash occurs. That kind of intelligent intervention can save lives, and is within reach,” he says.

At the same time, he emphasises that neither rules nor sensor technology alone can solve the problem.

“The big challenge with electric scooter riding is social norms and rider behaviour, and this does not disappear with regulations. Training is an important key to understanding how the vehicle should be handled and what you can, and cannot, do.

Rikard Fredriksson, Senior Advisor in Vehicle Safety at the Swedish Transport Administration and co-author of the study, agrees: 

“Alcohol is still a major problem for road safety in Sweden. Alcohol is involved in about 20 per cent of all fatal road crashes. This study shows that the number of alcohol-related fatalities involving electric scooters is more than twice as high, at 44 per cent. We are committed to the development of technology to counteract electric scooter driving under the influence of alcohol. It is also important to always wear a helmet, and to use only a vehicle that cannot exceed legal speed,” he says.  

The study, “Three modes, three profiles: Characterizing fatal crashes on e-scooters, e-bikes and conventional bicycles in Sweden”, has been published in the Journal of Safety Research. The authors are Rahul Rajendra Pai and Marco Dozza at Chalmers University of Technology, Sweden, as well as Rikard Fredriksson at the Swedish Transport Administration and Chalmers University of Technology.

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Move to quit: Exercise boosts smoking quit rates

Researchers found that people taking part in exercise programs were 15% more likely to achieve continuous abstinence and 21% more likely to report not smoking over a seven-day period, compared with control groups.

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A pack-a-day smoker can spend around $14,000 a year on cigarettes, yet despite the financial and health costs, quitting remains one of the most difficult changes many people will ever attempt.

Now, new research from Adelaide University shows that exercise can help people quit smoking by reducing cigarette consumption, easing cravings and improving their chances of quitting.

Researchers found that people taking part in exercise programs were 15% more likely to achieve continuous abstinence and 21% more likely to report not smoking over a seven-day period, compared with control groups.

They also found that exercise could reduce cigarette consumption by two cigarettes per day, and that a single bout of exercise immediately reduced cigarette cravings for up to 30 minutes after exercise.

The systematic review and meta-analysis examined 59 randomised controlled trials involving more than 9000 participants, exploring the effects of both single bouts of exercise and long-term exercise programs on smoking cessation, cravings, withdrawal symptoms and mood.

Globally, tobacco smoking remains the leading preventable cause of premature morbidity and mortality, accounting for about 7 million deaths, including an estimated 1.6 million non-smokers who are exposed to second-hand smoke.

Around the world, e-cigarette use has now reached more than 100 million people.

The researchers say exercise should be viewed as an additional tool that can be used alongside established smoking cessation support.

Lead researcher, Dr Ben Singh said the findings provide smokers with a practical, low-cost tool that can support their quitting journey.

“Quitting smoking is one of the best things a person can do for their health, but it’s also one of the hardest,” Dr Singh said.

“Many smokers want to quit, but the current approaches don’t work for everyone. That’s why we need more strategies that people can incorporate into their daily lives at little or no cost.

“Something as simple as regular exercise can make a meaningful difference to people trying to quit, helping them manage cravings, smoke less and improve their chances of quitting.”

While smoking rates have reduced over the past two decadesdemand for e-cigarettes and heated-tobacco products have risen, targeting the younger generation.

Today, 80% of the 1.3 billion tobacco users worldwide live in low- and middle-income countries, yet in contrast, vaping has risen across many OECD countries.

Senior researcher Adelaide University’s Professor Carol Maher said exercise could be used strategically to ward off tobacco cravings.

“Quitting smoking does not have to begin and end with willpower alone,” Prof Maher said.

“Cravings can be difficult to manage, but they often pass. Our review found that even a single bout of exercise can reduce cravings for up to 30 minutes, which may help people get through some of the hardest moments of a quit attempt.

“Exercise should not replace evidence-based quit supports such as counselling and smoking cessation medication, but it may be a practical, low-cost strategy that people can use alongside them.”

The researchers say the next step is to test how exercise can be built into real-world quit programs, including digital, community and clinical services, and to examine whether it can also support people trying to quit vaping, where evidence is currently lacking.

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Why taking a sick day depends on more than being sick

The study revealed a clear divide: workers in casual and fixed term jobs take only around one day of sick leave a year on average, compared with about four days for permanent employees.

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As winter illness spreads and households face cost-of-living pressure, many Australians cannot treat a sick day as a simple health decision. They may be too sick to work – but their job is too insecure to stay home.

New research led by the University of Technology Sydney (UTS) shows the decision is heavily influenced by pay, job security and gender. The study, published in Applied Economics, examines how workers’ health and economic circumstances dictate how many sick days they actually take.

“Employers and policymakers often focus on reducing absence, but workers who attend while unwell may recover more slowly, spread infection to colleagues, and be less productive,” said lead researcher Dr Nancy Kong, a Senior Research Fellow at the UTS Centre for Health Economics Research & Evaluation.

Drawing on data from the Household, Income and Labour Dynamics in Australia (HILDA) survey from more than 15,000 Australians between 2005 and 2016, Dr Kong and her co-authors, Dr David Rowell from the University of Queensland and Professor Peter Zweifel from the University of Zurich, examined patterns of sick leave across the workforce. 

“We focused on this period to avoid the COVID years, when major changes in public health rules, workplace practices and leave policies occurred at the same time, and could have blurred the relationship between job conditions and sick leave,” said Dr Kong.

The study revealed a clear divide: workers in casual and fixed term jobs take only around one day of sick leave a year on average, compared with about four days for permanent employees.

Even accounting for variables such as occupation, job satisfaction, household circumstances, living arrangements, marital status, education and place of residence, non-permanent workers still take around three fewer sick days each year.

“This does not necessarily mean casual and fixed-term workers are healthier,” said Dr Kong.

“A more likely explanation is that taking time off is riskier when work is insecure. Non-permanent workers may have less access to paid sick leave. They may also worry that saying no to work, even when ill, could affect future hours or their chances of keeping their job.”

“For a permanent employee, staying home with influenza might be inconvenient; but for a casual worker it may trigger financial stress.”

The study also found that economic insecurity plays a role, with workers living in areas with higher unemployment tending to take less sick leave.

For instance, when the local unemployment rate rises by five percentage points, sick leave drops. While this amounts to a fraction of a day per individual, across a standard team this adds up to significant forgone recovery time.  

This pattern is consistent with a simple concern: when jobs feel harder to replace, workers may be less willing to take time off.

“They may worry that being absent could make them seem less reliable or increase the risk of losing work,” said Dr Kong.

The effect of wages proved more nuanced. Higher wages alone did not consistently dictate leave behaviour. However, among workers in poorer health, higher wages were strongly associated with taking more sick leave, suggesting higher income earners possess a financial buffer.

“Higher-paid workers generally have workplace support and leave entitlements that mean they are supported to take time off when they are unwell without fear of a potential financial penalty,” said Dr Kong.

The most consistent finding was a distinct gender gap.  Across every analysis, men take fewer sick days than women, averaging about half a day less per year (a 23% difference), even when matching with similar health and job circumstances.

“This may reflect differences in health needs, caring responsibilities or how likely people are to seek medical care,” Dr Kong said. 

“But it also points to workplace cultures and gender expectations about ‘toughness’, reliability and working through illness.”

Ultimately, the study highlights that sick leave rates are not simply a reflection of physical health. For employers, low sick leave rates should not be automatically viewed as a sign of success; they may also indicate a culture of fear.

“Workplace cultures should not reward people for attending when unwell or treat legitimate sick leave as a lack of commitment,” said Dr Kong.

“Reducing stigma is also particularly important in addressing the gender gap.”

Dr Kong said for policymakers, the study points to the importance of secure work, accessible paid leave and workplace practices that support people to recover when unwell.

This is particularly relevant during periods of increased cost-of-living pressure, workforce shortages and seasonal illness.

“A fair and effective sick leave system should support productivity while ensuring workers do not have to choose between protecting their health and protecting their income.”

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