Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk

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Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk. / Miles, Amy E; Dos Santos, Fernanda C; Byrne, Enda M et al.

I: Neuropsychopharmacology, Bind 46, Nr. 13, 12.2021, s. 2304-2311.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Miles, AE, Dos Santos, FC, Byrne, EM, Renteria, ME, McIntosh, AM, Adams, MJ, Pistis, G, Castelao, E, Preisig, M, Baune, BT, Schubert, KO, Lewis, CM, Jones, LA, Jones, I, Uher, R, Smoller, JW, Perlis, RH, Levinson, DF, Potash, JB, Weissman, MM, Shi, J, Lewis, G, Penninx, BWJH, Boomsma, DI, Hamilton, SP, Sibille, E, Hariri, AR, Nikolova, YS & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2021, 'Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk', Neuropsychopharmacology, bind 46, nr. 13, s. 2304-2311. https://doi.org/10.1038/s41386-021-01189-x

APA

Miles, A. E., Dos Santos, F. C., Byrne, E. M., Renteria, M. E., McIntosh, A. M., Adams, M. J., Pistis, G., Castelao, E., Preisig, M., Baune, B. T., Schubert, K. O., Lewis, C. M., Jones, L. A., Jones, I., Uher, R., Smoller, J. W., Perlis, R. H., Levinson, D. F., Potash, J. B., ... Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2021). Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk. Neuropsychopharmacology, 46(13), 2304-2311. https://doi.org/10.1038/s41386-021-01189-x

CBE

Miles AE, Dos Santos FC, Byrne EM, Renteria ME, McIntosh AM, Adams MJ, Pistis G, Castelao E, Preisig M, Baune BT, et al. 2021. Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk. Neuropsychopharmacology. 46(13):2304-2311. https://doi.org/10.1038/s41386-021-01189-x

MLA

Vancouver

Miles AE, Dos Santos FC, Byrne EM, Renteria ME, McIntosh AM, Adams MJ et al. Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk. Neuropsychopharmacology. 2021 dec.;46(13):2304-2311. https://doi.org/10.1038/s41386-021-01189-x

Author

Miles, Amy E ; Dos Santos, Fernanda C ; Byrne, Enda M et al. / Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk. I: Neuropsychopharmacology. 2021 ; Bind 46, Nr. 13. s. 2304-2311.

Bibtex

@article{66539d559957499aab06086c3cec983c,
title = "Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk",
abstract = "Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing 'depression-like' shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = -3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997-1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10-4) in one cohort (N = 762, 48% men). Depression-like shifts in cortical gene expression have sex-specific effects on brain morphology and may contribute to broad depression vulnerability in men.",
keywords = "AMYGDALA, ASSOCIATION, DISORDERS, DSM-IV, ONSET, Genetic Predisposition to Disease, Humans, Transcriptome, Male, Multifactorial Inheritance, Depressive Disorder, Major/genetics, Young Adult, Brain/diagnostic imaging, Depression/genetics, Female",
author = "Miles, {Amy E} and {Dos Santos}, {Fernanda C} and Byrne, {Enda M} and Renteria, {Miguel E} and McIntosh, {Andrew M} and Adams, {Mark J} and Giorgio Pistis and Enrique Castelao and Martin Preisig and Baune, {Bernhard T} and Schubert, {K Oliver} and Lewis, {Cathryn M} and Jones, {Lisa A} and Ian Jones and Rudolf Uher and Smoller, {Jordan W} and Perlis, {Roy H} and Levinson, {Douglas F} and Potash, {James B} and Weissman, {Myrna M} and Jianxin Shi and Glyn Lewis and Penninx, {Brenda W J H} and Boomsma, {Dorret I} and Hamilton, {Steven P} and Etienne Sibille and Hariri, {Ahmad R} and Nikolova, {Yuliya S} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Manuel Mattheisen and Esben Agerbo and Buttensch{\o}n, {Henriette N{\o}rm{\o}lle} and Christensen, {Jane Hvarregaard} and Jakob Grove and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Per Qvist and Mortensen, {Preben Bo} and Anders B{\o}rglum",
note = "{\textcopyright} 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.",
year = "2021",
month = dec,
doi = "10.1038/s41386-021-01189-x",
language = "English",
volume = "46",
pages = "2304--2311",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "13",

}

RIS

TY - JOUR

T1 - Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk

AU - Miles, Amy E

AU - Dos Santos, Fernanda C

AU - Byrne, Enda M

AU - Renteria, Miguel E

AU - McIntosh, Andrew M

AU - Adams, Mark J

AU - Pistis, Giorgio

AU - Castelao, Enrique

AU - Preisig, Martin

AU - Baune, Bernhard T

AU - Schubert, K Oliver

AU - Lewis, Cathryn M

AU - Jones, Lisa A

AU - Jones, Ian

AU - Uher, Rudolf

AU - Smoller, Jordan W

AU - Perlis, Roy H

AU - Levinson, Douglas F

AU - Potash, James B

AU - Weissman, Myrna M

AU - Shi, Jianxin

AU - Lewis, Glyn

AU - Penninx, Brenda W J H

AU - Boomsma, Dorret I

AU - Hamilton, Steven P

AU - Sibille, Etienne

AU - Hariri, Ahmad R

AU - Nikolova, Yuliya S

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Mattheisen, Manuel

AU - Agerbo, Esben

AU - Buttenschøn, Henriette Nørmølle

AU - Christensen, Jane Hvarregaard

AU - Grove, Jakob

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - Qvist, Per

AU - Mortensen, Preben Bo

AU - Børglum, Anders

N1 - © 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.

PY - 2021/12

Y1 - 2021/12

N2 - Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing 'depression-like' shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = -3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997-1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10-4) in one cohort (N = 762, 48% men). Depression-like shifts in cortical gene expression have sex-specific effects on brain morphology and may contribute to broad depression vulnerability in men.

AB - Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing 'depression-like' shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = -3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997-1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10-4) in one cohort (N = 762, 48% men). Depression-like shifts in cortical gene expression have sex-specific effects on brain morphology and may contribute to broad depression vulnerability in men.

KW - AMYGDALA

KW - ASSOCIATION

KW - DISORDERS

KW - DSM-IV

KW - ONSET

KW - Genetic Predisposition to Disease

KW - Humans

KW - Transcriptome

KW - Male

KW - Multifactorial Inheritance

KW - Depressive Disorder, Major/genetics

KW - Young Adult

KW - Brain/diagnostic imaging

KW - Depression/genetics

KW - Female

U2 - 10.1038/s41386-021-01189-x

DO - 10.1038/s41386-021-01189-x

M3 - Journal article

C2 - 34588609

VL - 46

SP - 2304

EP - 2311

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 13

ER -