Genetic markers of white matter integrity in schizophrenia revealed by parallel ICA.

Frontiers in Human Neuroscience
Cota Navin GuptaVince D Calhoun

Abstract

It is becoming a consensus that white matter integrity is compromised in schizophrenia (SZ), however the underlying genetics remains elusive. Evidence suggests a polygenic basis of the disorder, which involves various genetic variants with modest individual effect sizes. In this work, we used a multivariate approach, parallel independent component analysis (P-ICA), to explore the genetic underpinnings of white matter abnormalities in SZ. A pre-filtering step was first applied to locate 6527 single nucleotide polymorphisms (SNPs) discriminating patients from controls with a nominal uncorrected p-value of 0.01. These potential susceptibility loci were then investigated for associations with fractional anisotropy (FA) images in a cohort consisting of 73 SZ patients and 87 healthy controls (HC). A significant correlation (r = -0.37, p = 1.25 × 10(-6)) was identified between one genetic factor and one FA component after controlling for scanning site, ethnicity, age, and sex. The identified FA-SNP association remained stable in a 10-fold validation. A 5000-run permutation test yielded a p-value of 2.00 × 10(-4). The FA component reflected decreased white matter integrity in the forceps major for SZ patients. The SNP component was ove...Continue Reading

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Citations

Jan 7, 2016·Journal of Child Psychology and Psychiatry, and Allied Disciplines·Yihong Zhao, F Xavier Castellanos
Dec 15, 2015·NeuroImage·Paul M ThompsonUNKNOWN ENIGMA Consortium
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Feb 7, 2020·Neurology. Neuroimmunology and Neuroinflammation·Muthuraman MuthuramanSergiu Groppa
Dec 5, 2018·BMC Molecular Biology·Leiah M Luoma, Fred B Berry

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Methods Mentioned

BETA
imaging techniques
genotyping

Software Mentioned

PLINK
Dtifit
FNIRT ( FMRIB Non - linear Image Registration Tool ; FSL
ICA
SPM
Matlab
FMRIB Software Library ( FSL
BeadStudio
FSL
FLIRT Linear Image Registration Tool )

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