Magazine: Spring 2026

Research: Teething Pain

Studies find factors underlying oral health challenges

By Michele Dula Baum

The Center for Oral Health in Research Appalachia (COHRA) was established in 2000 by the University of Pittsburgh and West Virginia University to investigate the genetic, microbial, and social factors contributing to high rates of tooth decay, known in dental parlance as caries.

“Appalachia has some of the worst health outcomes in the country and is very close to the bottom in terms of oral health,” says Distinguished Professor Mary Marazita, PhD, codirector of the Center for Craniofacial and Dental Genetics, School of Dental Medicine. “Our consortium was formed to tease out the factors that contribute to that poor oral health to see what we can do to improve it.”

Over the past 26 years, researchers affiliated with COHRA have been able to pinpoint important risk factors for dental disease, including fear and anxiety that can be transmitted across generations, as well as lack of access to fluoridated water or professional dental services. Several genetic areas of interest have also been identified that may play a role in a higher risk of caries as well as protection from decay.

COHRA investigators, including Marazita, who has a secondary appointment in the Department of Human Genetics, School of Public Health, and John Shaffer, PhD, department associate professor and vice chair for education, have coauthored hundreds of publications using COHRA data.

The Appalachian region spans 205,000 square miles stretching from the northern part of Mississippi, Alabama and Georgia up through the southern part of New York and includes all of West Virginia. Approximately 25 million people live in 420 counties and 13 states spread along the Appalachian mountain range.

“We started in West Virginia and very Western Pennsylvania and then added Pittsburgh, eventually, as the urban site, beginning in Braddock. Then we spread out to other clinics in the Pittsburgh area,” continues Marazita, explaining that the addition of Pittsburgh (the largest city in Appalachia) gave researchers an opportunity to compare rural and urban populations.

The COHRA 1 study cohort (2002-2009) surveyed more than 700 families from rural West Virginia, rural areas of Bradford and Burgettstown, Pennsylvania, and Braddock who had at least one child between the ages of 1 and 18. Assessments included interviews and questionnaires; a dental screening; collection of DNA and microbial samples; and collection of drinking water for analysis of fluoride content.

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"Children are especially vulnerable to tooth decay. Missed school is a huge problem."

John Shaffer

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"Appalachia has some of the worst health in the country and is very close to the bottom in terms of oral health." 

Mary Marazita

In 2011, the COHRA 2 study cohort began recruiting pregnant women from West Virginia and southwest Pennsylvania and followed them and their babies until the children reached age 6. Researchers collected similar data to COHRA 1, including medical, diet, childcare, and psychosocial specifics. “We collected lots of samples from people and from their houses, and we’re still analyzing them to this day,” says Marazita, explaining that as studies on these data progress, results will indicate interactions between the oral microbiome, host genetics, and a range of environmental factors that lead to high rates of caries in young Northern Appalachian children.

“There’s not one gene for cavities. That would be easy,” says Shaffer. “There’s certainly tens—probably hundreds—of genes that have a very small impact on cavities, but they all come together to create a profile for a particular person.”

Cavities are more than just a pain in the mouth. “Dental caries are responsible for the most missed days of work of any chronic human condition,” Marazita says.

“This is a thing I think a lot of people don’t appreciate because they’re not the ones that have untreated decay and are suffering,” adds Shaffer. “They’ve had a cavity that their dentist has spotted early, had a filling, and it’s never impacted their lives. They can’t even imagine.”

Children are especially vulnerable to tooth decay. “Missed school is a huge problem,” says Shaffer, adding that oral diseases include periodontitis and cancer. “We’re learning more about how someone’s oral health impacts their cardiovascular health, and very likely cognitive decline over time. It’s a chronic infection that’s bad for your body.”

With new R01 funding from the National Institute of Dental and Craniofacial Research, Shaffer and coprincipal investigator Kimon Divaris, DDS, PhD, chair of the Department of Pediatric Dentistry and Dental Public Health at the University of North Carolina, Chapel Hill, are taking the COHRA model of Appalachian studies international.

With $2.2 million over three years, the project, “Advancing the Genomics Knowledge Base for Oral Diseases,” will compile the largest genome-wide association scans of dental caries and periodontitis, develop polygenic risk scores, and identify gene-by-environment interactions in a research consortium of over 800,000 adult participants of at least 27 studies. Results may inform aspects of underlying biology, DNA-based risk assessment, and help design interventions to improve oral health.

“This is a precision medicine and public health kind of idea—to find out how we could tailor somebody’s treatment or preventive strategies toward their own specific genetics or risk profile,” says Shaffer.