Can Your Genes Determine How Much You Smoke?

RGC research reveals rare variants in CHRNB3 gene associated with reduced cigarette consumption.

Regeneron

March 11, 2026

Key Findings:

Rare variants in the CHRNB3 gene may be linked to reduced cigarette consumption
Discovery made across three diverse population cohorts
Carriers of specific variants smoked up to 78% fewer cigarettes
Research highlights the importance of studying diverse ancestries

At Regeneron Genetics Center^® (RGC), we're constantly searching for genetic insights that could transform how we treat challenging conditions. Our latest discovery — rare genetic variants that naturally protect against heavy smoking — advances our understanding of the genetic components that may drive smoking behavior.

In a study published in Nature Communications, RGC scientists analyzed genetic data from traditionally understudied populations and identified rare variants in the CHRNB3 gene that are associated with significantly reduced cigarette consumption. The CHRNB3 gene encodes the β3 subunit of the nicotinic acetylcholine receptor, a key component in how nicotine affects the brain.

Scientist working at the Regeneron Genetics Center on gene CHRNB3

"We're interested in these protective genetic changes because they show us how some people may naturally resist addiction, offering insights into the biological targets that influence smoking patterns," said Giovanni Coppola, MD, Vice President, RGC. "The approach of developing therapies that mimic naturally occurring protective genetic variants has already proven effective in other areas, such as cholesterol-lowering medications developed after scientists identified people with genetic changes that naturally kept their cholesterol levels low."

How do shared genetic patterns strengthen this discovery?

What makes this finding compelling is that we observed it independently across three distinct population cohorts – the Mexico City Prospective Study (MCPS), which included participants of Indigenous Mexican ancestry, Biobank Japan, which included participants of East Asian ancestry, and the UK Biobank, which included participants of European ancestry – all showing remarkably similar effect sizes.

"The fact that three distinct variants — one enriched in people of Indigenous Mexican ancestry, one in East Asians, and an aggregate signal in Europeans — all point to the same gene and produce remarkably similar effect sizes is, in our view, one of the strongest aspects of this study," explained Giovanni. "In genetics, when nature independently arrives at the same answer across a variety of populations, it strongly suggests that we have identified something biologically fundamental rather than a statistical artifact."

In the MCPS, carriers of the Indigenous Mexican variant smoked, on average, about 21% fewer cigarettes per day compared to non-carriers. Even more strikingly, individuals who carried two copies of the variant — essentially a natural knockout of the gene — smoked approximately 78% fewer cigarettes per day.

How could this genetic discovery lead to potential treatment?

Person holding a lit cigarette over an ashtray

This research provides the first direct human genetic evidence that a loss of CHRNB3 function reduces cigarette consumption. These findings both advance our understanding of smoking behavior and highlight why studying diverse populations matters. Without including these underrepresented populations, these rare yet significant variants might have remained undiscovered."

"Genetic evidence suggests that inhibiting CHRNB3 could help reduce or stop smoking, but it's too early to confirm whether a treatment is possible and, if so, whether it would be efficacious or safe," Giovanni noted. "Several key questions remain, such as understanding how the gene influences smoking and its other roles in the brain."

Smoking addiction is a complex behavioral trait influenced by biological, psychological, and social factors, making it challenging to address with a single therapeutic approach. Although existing treatments demonstrate reasonable efficacy, the field has experienced minimal innovation over the past two decades. A fundamental challenge has been identifying new, robust biological targets that can be mimicked or targeted with therapies. Human genetics can offer a potential breakthrough path — by identifying individuals naturally protected from heavy smoking due to their genetic makeup, we can pinpoint precise biological mechanisms worth targeting, as demonstrated in our CHRNB3 study.

Why does genetic diversity matter in research?

Population diversity has always been a cornerstone of RGC's research strategy. This discovery of a rare variant underscores the critical importance of studying diverse ancestries.

"This study is a testament to the value of studying representative populations in genomic research," added Giovanni. "The key discovery—the p.Glu284Gly variant—exists almost exclusively in people of Indigenous Mexican ancestry. Had we only studied Europeans, as most genomic studies historically have, we would have missed it entirely. Representative research is not just an ethical imperative, it is a scientific one."

What could be the next steps for this research?

Potential next steps would include two complementary approaches. First, conducting thorough health assessments in Mexico could provide insights about people who have this protective variation, with particular interest in those rare individuals who carry two copies and are effectively natural knockouts of CHRNB3. At the same time, functional studies are needed to understand how the absence of this protein helps people smoke less.

"Findings like ours are a reminder that for many people, struggling to control how much they smoke is not a failure of willpower, it is biology," said Giovanni. "Some people are truly wired differently, and understanding that wiring is the first step toward developing better tools to help them."