How genetic analysis can help explain which people will benefit most and least from GLP-1 medications
By effectively controlling blood sugar and body weight, GLP-1 medications have revolutionized the management of type 2 diabetes and obesity and help to protect individuals from developing cardiovascular disease. However, not everyone responds to GLP-1s in the same way. Around 10% of people do not lose any weight, and some only experience weight loss initially, before their body weight plateaus. These differences may be explained by genetic factors.
In this study, scientists are searching for genetic predictors of weight loss among ~10,000 Kaiser Permanente Research Bank participants who were prescribed a GLP-1. Identifying genetic differences between people who lost weight and people who didn’t may help us better understand which treatment is best for each person; this is known as precision medicine. This kind of testing could streamline and improve treatment for diabetes and obesity. These discoveries could also shed light on the biological mechanisms that allow effective GLP-1 treatment. This understanding will improve scientists’ and physicians’ understanding of diseases and inform the design of next-generation treatments.
Telomere length, genetics, aging, and health
What are telomeres and how are they related to aging? Telomeres are protective “caps” on chromosomes that get shorter as we get older. The length of telomeres may indicate “biological aging.” Biological aging, in contrast to actual aging, or how many years someone has lived, refers to the fact that the aging process is very different for each of us. These differences are based on genes, various diseases people may develop over time, and different types of environmental exposures and trauma experienced in one’s lifetime.
Shorter telomeres have been linked to many age-related conditions, but most prior studies have focused on people of European ancestry. We still don’t fully understand how genetics, lifestyle, and social and neighborhood characteristics interact to shape telomere length and disease risk in people from different ancestries.
Using data from the Kaiser Permanente Research Bank, scientists will study how these different factors are linked to telomere length, which will clarify how various social and biological forces influence aging. This study could help create important scientific information that supports future research on specific health conditions and diseases. For example, patients and their families may benefit from learning information about disease risk and prevention that is more specific to them and their background. Clinicians and health systems may be able to use findings to improve screening and counseling for people from different ancestries. Researchers will gain clearer evidence about the pathways linking aging, environment, and genetics. Policymakers and public health leaders may use results to design more equitable, community-focused strategies. Ultimately, this work aims to reduce health disparities and improve aging outcomes for people of all backgrounds.
Which biological factors signal the risk for developing ALS?
Amyotrophic lateral sclerosis (ALS) is a devastating disease with no cure. Most studies of ALS use blood samples taken after someone is diagnosed, when a lot of nerve damage has already happened. This project will study blood samples from people before they developed ALS and compare them with samples from healthy people of the same age and sex. Using advanced protein-testing methods, scientists will search for early signs in the body that may predict who will develop ALS as well as any factors that may influence how quickly the disease progresses. They will also test whether certain immune and autoimmune conditions are connected to a higher risk of ALS. The results may lead to new ways to diagnose ALS earlier and identify people at risk, which could ultimately guide the development of better treatments. People with ALS, their families, and the broader medical community will benefit from the insights gained through this research.
A global study of the genetic and environmental factors that affect tobacco and alcohol use
Tobacco and alcohol use cause over 11 million deaths worldwide each year, making them the leading preventable causes of death. A person’s genes and environment affect whether they start smoking or drinking, why some people become heavy users, and why some people have trouble quitting. This research will combine genetic information from more than 5.5 million volunteers from many various backgrounds and countries.
By studying millions of genetic variations across various populations and environments, scientists hope to better understand which genetic factors increase the risk of tobacco and alcohol use. They will also study how genes and environmental factors — such as local laws, culture, and social habits — work together to increase or lower these risks.
Learning how genes and environmental factors affect cigarette smoking and alcohol use can help scientists create better ways to prevent these behaviors, improve predictions about who may be at risk, and develop treatments that work better for people from specific backgrounds and communities. Who will benefit? Everyone: people curious about their own risks, doctors seeking targeted therapies, public-health officials designing smarter policies, and researchers working to close health equity gaps across all populations.
