Genetic risk for schizophrenia is associated with increased proportion of indirect connections in brain networks revealed by a semi-metric analysis: evidence from population sample stratified for polygenic risk

S I Dimitriadis*, G Perry, T M Lancaster, K E Tansey, K D Singh, P Holmans, A Pocklington, G Davey Smith, S Zammit, J Hall, M C O'Donovan, M J Owen, D K Jones, D E Linden

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Research studies based on tractography have revealed a prominent reduction of asymmetry in some key white-matter tracts in schizophrenia (SCZ). However, we know little about the influence of common genetic risk factors for SCZ on the efficiency of routing on structural brain networks (SBNs). Here, we use a novel recall-by-genotype approach, where we sample young adults from a population-based cohort (ALSPAC:N genotyped = 8,365) based on their burden of common SCZ risk alleles as defined by polygenic risk score (PRS). We compared 181 individuals at extremes of low (N = 91) or high (N = 90) SCZ-PRS under a robust diffusion MRI-based graph theoretical SBN framework. We applied a semi-metric analysis revealing higher SMR values for the high SCZ-PRS group compared with the low SCZ-PRS group in the left hemisphere. Furthermore, a hemispheric asymmetry index showed a higher leftward preponderance of indirect connections for the high SCZ-PRS group compared with the low SCZ-PRS group (PFDR < 0.05). These findings might indicate less efficient structural connectivity in the higher genetic risk group. This is the first study in a population-based sample that reveals differences in the efficiency of SBNs associated with common genetic risk variants for SCZ.

Original languageEnglish
Article numberbhac256
Number of pages15
JournalCerebral Cortex
Publication statusE-pub ahead of print - 14 Jul 2022


  • AGE
  • Avon Longitudinal Study of Parents and Children (ALSPAC)
  • brain connectomics
  • diffusion magnetic resonance imaging (dMRI)
  • genetic risk for schizophrenia
  • schizophrenia
  • semi-metric percentage
  • structural brain networks
  • tractography

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