By simultaneously investigating millions of gene variants in more than 5,000 individuals, researchers at the University of North Carolina at Chapel Hill reveal that genes responsible for nervous system development and immune function also play a role in an insidious gum disease known as chronic periodontitis.
The work is the first genome-wide association study of the disease, offering an unparalleled breadth of insight into its genetics and how it is affected by environmental factors such as smoking.
The study was led by Kimon Divaris, PhD, research assistant professor in the Department of Pediatric Dentistry, who received his doctorate in epidemiology at the Gillings School of Global Public Heath in December 2011. Andrew Olshan, PhD, epidemiology professor and chair of the department; Keri L. Monda, PhD, research assistant professor of epidemiology; Kari E. North, PhD, associate professor of epidemiology; and Ethan Lange, PhD, research assistant professor of biostatistics, are also co-authors of the study. Periodontitis is a serious infection and inflammation of the gums that can progressively destroy the bone and tissues that support your teeth, said Divaris, whose work appears in the March 4 issue of Human Molecular Genetics. Now we not only confirm that this is a heritable disease, which occurs in some form in nearly 50 percent of the population, but we also know which genes play a large role and that gives us pretty interesting clues about how the disease works and what we can do to better treat and prevent it.
Divaris and his team identified six genes and twelve pathways important to nervous system and immune function that are involved in the disease. Variants of those genes potentially could increase or decrease peoples risk of developing periodontitis, dependent upon how these genes interact with one another and with their environment.
Based on their findings, Divaris and his team propose that genes in the immune system and the nervous system play off one another to predispose people to chronic periodontitis and that smoking interacts with these genes to increase that risk. One hypothesis is that when bacteria that live on and beneath our gums become harmful, the nervous system sends signals to elicit an immune response to scale back the infection. That response leads to inflammation and possible destruction of the tooth-supporting gums and tissues.
The study employed, for the first time, a genome-wide association analysis approach a methodology that allowed the simultaneous investigation of millions of genetic markers (loci) across the human genome for potential associations with chronic periodontitis among a large sample of approximately 5,000 individuals enrolled in the Atherosclerosis Risk in Communities (ARIC) study. The investigation highlighted several novel regions of the human genome, genes and pathways that may be associated with increased risk for the development of periodontitis.
The study examined interactions between genetic and environmental effects and identified genome-wide significant synergistic effects between genetic factors and smoking. Additional analyses revealed a significant role of nervous system, neurotransmitter and immune response pathways in the risk for chronic periodontitis.
Olshan says the multidisciplinary approach was pivotal to the study's findings.
"Periodontitis and the general microbiome have emerged as major contributors to a variety of health conditions of public health significance," Olshan says. "We are very excited that the project has led to important findings. That it represents a collaborative effort by an epidemiology doctoral student and faculty members in the dental school and school of public health and utilizes a well-known epidemiologic cohort resource is especially noteworthy."
Genome-wide analyses for this study were undertaken at the genetic epidemiology laboratory at the UNC Gillings School of Global Public Health at the University of North Carolina at Chapel Hill. Funding was provided by multiple grants from the National Institutes of Health.
The manuscript is available online.
Olshan says the multidisciplinary approach was pivotal to the study's findings.
"Periodontitis and the general microbiome have emerged as major contributors to a variety of health conditions of public health significance," Olshan says. "We are very excited that the project has led to important findings. That it represents a collaborative effort by an epidemiology doctoral student and faculty members in the dental school and school of public health and utilizes a well-known epidemiologic cohort resource is especially noteworthy."
Genome-wide analyses for this study were undertaken at the genetic epidemiology laboratory at the UNC Gillings School of Global Public Health at the University of North Carolina at Chapel Hill. Funding was provided by multiple grants from the National Institutes of Health.
The manuscript is available online.
Gillings School of Global Public Health contact: David Pesci, director of communications, (919) 962-2600 or dpesci@unc.edu.