Researchers at the Johns Hopkins University School of
Medicine are one gene closer to
understanding schizophrenia and related disorders.
Reporting in the Jan. 9 issue of The American
Journal of Human Genetics, the team describes how a
variation in the neuregulin 3 gene influences
delusions associated with schizophrenia.
"Neuregulin 3 is clearly one more gene to add to the
few currently known to contribute to
schizophrenia," said David Valle, director of the
McKusick-Nathans Institute of Genetic Medicine at
Johns Hopkins. "There's much more to do, but we're making
Schizophrenia is a varied condition with a number of
symptoms not shared by all affected. This
could be one reason why it's been difficult to identify
genes that contribute to the condition.
To address this, the team first rigorously separated
the 73 different symptoms associated
with the condition into nine distinct factors: prodromal,
negative, delusion, affective, scholastic,
adolescent sociability, disorganization, disability and
Then, using genetic samples from more than 450 people
with schizophrenia and their parents as
well as unrelated nonaffected people for comparison, the
team focused on one region of chromosome
10 that previously had been implicated to contain genes
that contribute to the condition. They
analyzed more than 1,400 single nucleotide polymorphisms,
or SNPs for short, to see if any particular
SNPs were more frequently carried by schizophrenia patients
than unaffected people.
They found three SNPs strongly associated with
delusions, and all three SNPs are located in
the neuregulin 3 gene. In fact, of the team's top 20 most
significant SNPs, 13 of them are located at
or near this gene; but rather than being associated with
delusion, the other SNPs are associated with
scholastic, disorganization and hallucination factors.
"Neuregulin 3 makes sense because it's turned on
mostly in the central nervous system, and the
related gene neuregulin 1 also has been shown to be
associated with schizophrenia," said Dimitrios
Avramopoulos, an associate professor of
psychiatry and a member of the Institute of Genetic
"We're still at the stage of trying to understand the
disease, figuring out what goes wrong in
the brain," he said.
The next step for the team, Avramopoulos said, is to
follow up and sequence the neuregulin 3
gene from a number of the patients in this study to look
for rare genetic variants that might also
contribute to the condition.
This study was funded by the National Institutes of
Health, National Institute of Mental
Health, Wasie Foundation and National Alliance for Research
on Schizophrenia and Depression. In
addition to Avramopoulos and Valle, authors on the paper
are Pei-Lung Chen, Virginia K. Lasseter, John
A. McGrath, M. Daniele Fallin, Kung-Yee Liang, Gerald
Nestadt, Ningping Feng, Gary Steel, Andrew S.
Cutting, Paula Wolyniec and Ann E. Pulver, all of Johns