By David Douglas
NEW YORK—A genome-wide association study (GWAS) in a largely Tamil population has implicated NAPRT1 as a novel schizophrenia-susceptibility gene, according to Australian and Indian researchers.
NAPRT1 "encodes an enzyme involved in vitamin B3 metabolism," Dr. Bryan J. Mowry of the University of Queensland, in Brisbane, explained in an email to Reuters Health. "We were also able to find this gene in a large dataset of schizophrenia patients with European ancestry."
The study, online July 3 in JAMA Psychiatry, involved more than 3,000 participants, of whom 1,321 had schizophrenia, 885 were family controls and 886 were unrelated controls. Starting in 2001, the research took place over the course of 18 years.
A significant new genome-wide association was observed between schizophrenia and the A allele of rs10866912 (odds ratio, 1.27). This allele directly modifies the abundance of the nicotinate phosphoribosyltransferase gene (NAPRT1) transcript in brain cortex.
"When we knocked out the NAPRT1 gene in zebrafish," continued Dr. Mowry, "brain development of the fish was impaired. We are now working to understand more deeply how this gene functions in the brain."
Because there is no other Indian schizophrenia GWAS, Dr. Mowry and his colleagues note in their paper, "It has not been possible to test replication of this finding." But, they add, "our locus was replicated in the European ancestry schizophrenia PGC2 GWAS with similar direction and smaller magnitude of effect," with a significant OR of 1.04.
"We'd like to look further into populations in India, to increase our sample size to see if we can replicate this result and discover additional variants that might be involved," Dr. Mowry added.
"There are no immediate benefits for clinical practice," he noted, "but this finding contributes to the expanding knowledge of potential underlying neurobiological mechanisms, which is essential for developing novel therapeutics."
An accompanying editorial notes that although many genetic risk factors for schizophrenia have already been reported, "the association at rs10866912 is new."
"First and foremost, replication in another independent South Indian sample is needed. It would also be of interest to investigate neighboring Indian ethnic groups with different ancestries," Dr. Vishwajit L. Nimgaonkar of the University of Pittsburgh School of Medicine, in Pennsylvania, and colleagues write.
SOURCE: https://bit.ly/2NM9wZB and https://bit.ly/2NMaaX1
JAMA Psychiatry 2019.
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