Schizophrenia is a mental disorder that affects how a person thinks, feels, and behaves. Many of the genetic variations that increase risk for schizophrenia
are rare, making it difficult to study their role in the disease.
overcome this, the Psychiatric Genomics Consortium, an international
team led by Jonathan Sebat at University of California San Diego
School of Medicine, analyzed the genomes of more than 41,000 people in
the largest genome-wide study of its kind to date.
‘Eight locations in the genome with copy number variants associated with schizophrenia risk have been identified by researchers.’
published in Nature Genetics
, reveals several regions of the genome where mutations increase schizophrenia risk between four- and 60-fold.
These mutations, known as copy number variants, are deletions or
duplications of the DNA sequence. A copy number variant may affect
dozens of genes, or it can disrupt or duplicate a single gene. This type
of variation can cause significant alterations to the genome and lead
to psychiatric disorders, said Sebat, who is a professor and chief of
the Beyster Center for Genomics of Neuropsychiatric Diseases at UC San
Diego School of Medicine. Sebat and other researchers previously
discovered that relatively large copy number variants occur more
frequently in schizophrenia than in the general population.
In this latest study, Sebat teamed up with more than 260 researchers
from around the world, part of the Psychiatric Genomics Consortium, to
analyze the genomes of 21,094 people with schizophrenia and 20,227
people without schizophrenia.
They found eight locations in the genome
with copy number variants associated with schizophrenia risk. Only a
small fraction of cases (1.4%) carried these variants. The
researchers also found that these copy number variants occurred more
frequently in genes involved in the function of synapses, the
connections between brain cells that transmit chemical messages.
With its large sample size, this study had the power to find copy
number variants with large effects that occur in more than 0.1%
of schizophrenia cases. However, the researchers said they are still
missing many variants. More analyses will be needed to detect risk
variants with smaller effects, or ultra-rare variants.
"This study represents a milestone that demonstrates what large
collaborations in psychiatric genetics can accomplish," Sebat said.
"We're confident that applying this same approach to a lot of new data
will help us discover additional genomic variations and identify
specific genes that play a role in schizophrenia and other psychiatric