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

Stavros L. Dimitriadis; Gavin Perry; Thomas Lancaster; Katherine Tansey; Khuraijam Dhanachandra Singh; P Holmans; Andrew Pocklington; George Davey Smith; Stanley  Zammit; J. Hall; Michael C O'Donovan; MJ Owen; Derek K.   Jones; DE Linden

doi:10.1093/cercor/bhac256

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

Stavros L. Dimitriadis^*, Gavin Perry, Thomas Lancaster, Katherine Tansey, Khuraijam Dhanachandra Singh, P Holmans, Andrew Pocklington, George Davey Smith, Stanley Zammit, J. Hall, Michael C O'Donovan, MJ Owen, Derek K. Jones, DE Linden

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

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

Original language	English
Article number	bhac256
Number of pages	15
Journal	Cerebral Cortex
DOIs	https://doi.org/10.1093/cercor/bhac256
Publication status	Published - 14 Jul 2022

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Bristol Population Health Science Institute

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

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Dimitriadis, S. L., Perry, G., Lancaster, T., Tansey, K., Singh, K. D., Holmans, P., Pocklington, A., Davey Smith, G., Zammit, S., Hall, J., O'Donovan, M. C., Owen, MJ., Jones, D. K., & Linden, DE. (2022). 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. Cerebral Cortex, Article bhac256. https://doi.org/10.1093/cercor/bhac256

@article{f3c4a0773eb2417cae94d9177c08a4c7,

title = "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",

abstract = "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 ",

author = "Dimitriadis, {Stavros L.} and Gavin Perry and Thomas Lancaster and Katherine Tansey and Singh, {Khuraijam Dhanachandra} and P Holmans and Andrew Pocklington and {Davey Smith}, George and Stanley Zammit and J. Hall and O'Donovan, {Michael C} and MJ Owen and Jones, {Derek K.} and DE Linden",

year = "2022",

month = jul,

day = "14",

doi = "10.1093/cercor/bhac256",

language = "English",

journal = "Cerebral Cortex",

issn = "1047-3211",

publisher = "Oxford University Press",

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Dimitriadis, SL, Perry, G, Lancaster, T, Tansey, K, Singh, KD, Holmans, P, Pocklington, A, Davey Smith, G, Zammit, S, Hall, J, O'Donovan, MC, Owen, MJ, Jones, DK & Linden, DE 2022, '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', Cerebral Cortex. https://doi.org/10.1093/cercor/bhac256

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. / Dimitriadis, Stavros L.; Perry, Gavin; Lancaster, Thomas et al.
In: Cerebral Cortex, 14.07.2022.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Genetic risk for schizophrenia is associated with increased proportion of indirect connections in brain networks revealed by a semi-metric analysis

T2 - Evidence from population sample stratified for polygenic risk

AU - Dimitriadis, Stavros L.

AU - Perry, Gavin

AU - Lancaster, Thomas

AU - Tansey, Katherine

AU - Singh, Khuraijam Dhanachandra

AU - Holmans, P

AU - Pocklington, Andrew

AU - Davey Smith, George

AU - Zammit, Stanley

AU - Hall, J.

AU - O'Donovan, Michael C

AU - Owen, MJ

AU - Jones, Derek K.

AU - Linden, DE

PY - 2022/7/14

Y1 - 2022/7/14

N2 - 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

AB - 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

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DO - 10.1093/cercor/bhac256

M3 - Article (Academic Journal)

C2 - 35830871

SN - 1047-3211

JO - Cerebral Cortex

JF - Cerebral Cortex

M1 - bhac256

ER -

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

Abstract

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

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