Researchers from North Carolina State University, UNC-Chapel Hill, and other institutions say they have taken the first steps toward creating a roadmap that may help scientists narrow down the genetic cause of numerous diseases. The work should also shed new light on how heredity and environment can affect gene expression, they add.

According to Fred Wright, Ph.D., NC State professor of statistics and biological sciences, director of NC State's Bioinformatics Center and co-first author of the study, “Everyone has the same set of genes. It's difficult to determine which genes are heritable, or controlled by your DNA, versus those that may be affected by the environment. Teasing out the difference between heredity and environment is key to narrowing the field when you're looking for a genetic relationship to a particular disease.”

Dr. Wright—with co-first author Patrick Sullivan, Ph.D., distinguished professor of genetics and psychiatry at UNC-Chapel Hill and director of the Center for Psychiatric Genomics, and national and international colleagues—analyzed blood sample data from 2,752 adult twins (both identical and fraternal) from the Netherlands Twin Register and an additional 1,895 participants from the Netherlands Study of Depression and Anxiety. For all 20,000 individual genes, they determined whether those genes were heritable or largely affected by environment.

“The most highly heritable genes (~777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation,” wrote the investigators. “The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness…. Our results provide a new resource toward understanding the genetic control of transcription.”

“Identical twins have identical DNA,” Dr. Wright explains, “so if a gene is heritable, its expression will be more similar in identical twins than in fraternal twins. This process allowed us to create a database of heritable genes, which we could then compare with genes that have been implicated in disease risk. We saw that heritable genes are more likely to be associated with disease—something that can help other researchers determine which genes to focus on in future studies.”

The study (“Heritability and genomics of gene expression in peripheral blood”) appears online in Nature Genetics.

“This is by far the largest twin study of gene expression ever published, enabling us to make a roadmap of genes versus environment,” according to Dr. Sullivan, adding that the study measured relationships with disease more precisely than had been previously possible, and uncovered important connections to recent human evolution and genetic influence in disease.

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