Media Contact: Ian Demsky

U-M among international group to find genetic variants that may contribute to mental illness

Several newly discovered genetic variants may increase the risk of developing bipolar disorder, schizophrenia or both, according to an international research consortium that includes the University of Michigan School of Public Health and U-M Health System.

Laura Scott, associate research scientist at U-M SPH, led the SPH group that participated along with more than 250 researchers from more than 20 countries that comprised the Psychiatric Genome-Wide Association Study Consortium. The various groups in the consortium found six variants not previously observed, and 11 variants total.

Researchers from U-M’s Molecular and Behavioral Neuroscience Institute included: Fan Meng, Ph.D., Robert C. Thompson, Ph.D., Margit Burmeister, Ph.D., Huda Akil, Ph.D. and Stanley J. Watson, M.D., Ph.D.

Scott said the U-M SPH study group focused on the bipolar analysis. She was one of the leaders of the consortium's bipolar analysis team, which also included biostatistics graduate student Phoenix Kwan and other members of the Michigan group. The team found two variants, one of which was novel, that were associated with increased risk of developing bipolar disorder and possibly other conditions.

The consortium's findings are published online in two papers in the journal Nature Genetics.

Together, the papers significantly advance understanding of what causes the two devastating brain disorders that each affect about 1 percent of the population. Family history, which reflects genetic inheritance, is a strong risk factor for both disorders, and the general assumption is that many genes, plus environmental factors, contribute to disease risk.

"The bipolar study's great strength truly is the large sample size that was brought together, 7,481 cases and 9,250 controls" Scott said.

Scott said the consortium's bipolar paper extends the findings of smaller studies from the Michigan study group, and other groups that examined genetic variants that occur frequently in the population. Research is underway at U-M SPH, led by Michael Boehnke, with collaborators at HudsonAlpha Institute for Biotechnology to learn about the genetic variants occur less frequently in people. The study team will perform whole genome sequencing of 2,000 bipolar cases and controls.

"To our knowledge, this is currently the largest whole genome sequencing project for bipolar disorder," Scott said. "The hypothesis is that there are bipolar risk variants that occur infrequently in the population but that these variants may actually have a stronger effect on bipolar disorder than the ones currently identified."

The genotyping and initial analyses of the samples contributed by Michigan was funded by the Pritzker Neuropsychatric Research Consortium. The consortium research was funded by several European, American and Australian funding bodies. Funds for coordination of the consortium were provided by the U.S. National Institute of Mental Health.

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