title: An exploratory association study of the influence of dysbindin and neuregulin polymorphisms on brain morphometry in patients with schizophrenia and healthy subjects from South India.
abstract: Multiple genetic risk variants may act in a convergent manner leading on to the pathophysiological alterations of brain structure and function in schizophrenia. We examined the effect of polymorphisms of two candidate genes that mediate glutamatergic signaling, viz., dysbindin (rs1011313) and neuregulin (rs35753505), on brain morphometry in patients with schizophrenia (N=38) and healthy subjects (N=37) from South India. Patients with schizophrenia showed trend-level (p<0.001 uncorrected, 20 voxel extent correction) volumetric reductions in multiple brain regions when compared to healthy control subjects. Trend-level volumetric differences were also noted between homozygotes of the risk allele (AA) of the neuregulin (NRG1) polymorphism and heterozygotes (AG), as well as homozygotes of the risk allele (CC) of the dysbindin (DTNBP1) polymorphism and heterozygotes (TC), irrespective of diagnosis. Moreover, an additive effect of the risk alleles on brain morphometry was also noted. These preliminary findings highlight the possible influence of polymorphisms of risk genes on brain morphometry in schizophrenia.
authors.affiliation: Multimodal Brain Image Analysis Laboratory (MBIAL), NIMHANS, Bangalore 560029, India; Department of Psychiatry, NIMHANS, Bangalore 560029, India. Electronic address: galaxie2485@yahoo.co.in.
authors.forename: Priyadarshini
authors.initials: P
authors.lastname: Thirunavukkarasu
authors.affiliation: Multimodal Brain Image Analysis Laboratory (MBIAL), NIMHANS, Bangalore 560029, India; Department of Psychiatry, NIMHANS, Bangalore 560029, India. Electronic address: av.anupa@gmail.com.
authors.forename: Anupa A
authors.initials: AA
authors.lastname: Vijayakumari
authors.affiliation: Multimodal Brain Image Analysis Laboratory (MBIAL), NIMHANS, Bangalore 560029, India; Department of Psychiatry, NIMHANS, Bangalore 560029, India; Department of Clinical Neuroscience, NIMHANS, Bangalore 560029, India. Electronic address: jpjnimhans@gmail.com.
authors.forename: John P
authors.initials: JP
authors.lastname: John
authors.affiliation: Multimodal Brain Image Analysis Laboratory (MBIAL), NIMHANS, Bangalore 560029, India; Department of Neurophysiology, NIMHANS, Bangalore 560029, India. Electronic address: hnharsha@gmail.com.
authors.forename: Harsha N
authors.initials: HN
authors.lastname: Halahalli
authors.affiliation: Department of Psychiatry, NIMHANS, Bangalore 560029, India; Molecular Genetics Laboratory, NIMHANS, Bangalore 560029, India. Electronic address: paul.pradipp@gmail.com.
authors.forename: Pradip
authors.initials: P
authors.lastname: Paul
authors.affiliation: Department of Psychiatry, NIMHANS, Bangalore 560029, India; Molecular Genetics Laboratory, NIMHANS, Bangalore 560029, India. Electronic address: sen.somdatta@gmail.com.
authors.forename: Somdatta
authors.initials: S
authors.lastname: Sen
authors.affiliation: Department of Psychiatry, NIMHANS, Bangalore 560029, India; Molecular Genetics Laboratory, NIMHANS, Bangalore 560029, India. Electronic address: meera.purushottam@gmail.com.
authors.forename: Meera
authors.initials: M
authors.lastname: Purushottam
authors.affiliation: Department of Psychiatry, NIMHANS, Bangalore 560029, India; Molecular Genetics Laboratory, NIMHANS, Bangalore 560029, India. Electronic address: sjain.nimhans@gmail.com.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Jain
mesh_terms: D000328:Adult; D000483:Alleles; D001921:Brain / Q000473:pathology*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D008279:Magnetic Resonance Imaging; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics*; D009929:Organ Size / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; C094131:NRG1 protein, human; D020890:Neuregulin-1
keywords: DTNBP1; Gray matter volumes; NRG1; Voxel based morphometry