Insulinopathies of the brain?: Genetic overlap between somatic insulin-related and neuropsychiatric disorders

Giuseppe Fanelli; Barbara Franke; Ward De Witte; I Hyun Ruisch; Jan Haavik; Veerle van Gils; Willemijn J Jansen; Stephanie J B Vos; Lars Lind; Jan K Buitelaar; Tobias Banaschewski; Søren Dalsgaard; Alessandro Serretti; Nina Roth Mota; Geert Poelmans; Janita Bralten

doi:10.1038/s41398-022-01817-0

Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders

Giuseppe Fanelli, Barbara Franke, Ward De Witte, I Hyun Ruisch, Jan Haavik, Veerle van Gils, Willemijn J Jansen, Stephanie J B Vos, Lars Lind, Jan K Buitelaar, Tobias Banaschewski, Søren Dalsgaard, Alessandro Serretti, Nina Roth Mota, Geert Poelmans, Janita Bralten

73 Citations (Scopus)

Abstract

The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer's disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain "insulinopathies" were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (rg = -0.315, p = 3.9 × 10-8), OCD and obesity (rg = -0.379, p = 3.4 × 10-5), and OCD and T2DM (rg = -0.172, p = 3 × 10-4). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p

Original language	English
Article number	59
Journal	Translational psychiatry
Volume	12
Issue number	1
Pages (from-to)	59
ISSN	2158-3188
DOIs	https://doi.org/10.1038/s41398-022-01817-0
Publication status	Published - 14 Feb 2022
Externally published	Yes

Keywords

Attention Deficit Disorder with Hyperactivity/psychology
Autism Spectrum Disorder/psychology
Brain
Depressive Disorder, Major/genetics
Diabetes Mellitus, Type 2/genetics
Genome-Wide Association Study
Humans
Insulin

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Fanelli, G., Franke, B., De Witte, W., Ruisch, I. H., Haavik, J., van Gils, V., Jansen, W. J., Vos, S. J. B., Lind, L., Buitelaar, J. K., Banaschewski, T., Dalsgaard, S., Serretti, A., Mota, N. R., Poelmans, G., & Bralten, J. (2022). Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders. Translational psychiatry, 12(1), 59. Article 59. https://doi.org/10.1038/s41398-022-01817-0

Fanelli, G, Franke, B, De Witte, W, Ruisch, IH, Haavik, J, van Gils, V, Jansen, WJ, Vos, SJB, Lind, L, Buitelaar, JK, Banaschewski, T, Dalsgaard, S, Serretti, A, Mota, NR, Poelmans, G & Bralten, J 2022, 'Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders', Translational psychiatry, vol. 12, no. 1, 59, pp. 59. https://doi.org/10.1038/s41398-022-01817-0

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abstract = "The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer's disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain {"}insulinopathies{"} were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (rg = -0.315, p = 3.9 × 10-8), OCD and obesity (rg = -0.379, p = 3.4 × 10-5), and OCD and T2DM (rg = -0.172, p = 3 × 10-4). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p ",

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T1 - Insulinopathies of the brain?

T2 - Genetic overlap between somatic insulin-related and neuropsychiatric disorders

AU - Fanelli, Giuseppe

AU - Franke, Barbara

AU - De Witte, Ward

AU - Ruisch, I Hyun

AU - Haavik, Jan

AU - van Gils, Veerle

AU - Jansen, Willemijn J

AU - Vos, Stephanie J B

AU - Lind, Lars

AU - Buitelaar, Jan K

AU - Banaschewski, Tobias

AU - Dalsgaard, Søren

AU - Serretti, Alessandro

AU - Mota, Nina Roth

AU - Poelmans, Geert

AU - Bralten, Janita

PY - 2022/2/14

Y1 - 2022/2/14

N2 - The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer's disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain "insulinopathies" were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (rg = -0.315, p = 3.9 × 10-8), OCD and obesity (rg = -0.379, p = 3.4 × 10-5), and OCD and T2DM (rg = -0.172, p = 3 × 10-4). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p

AB - The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer's disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain "insulinopathies" were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (rg = -0.315, p = 3.9 × 10-8), OCD and obesity (rg = -0.379, p = 3.4 × 10-5), and OCD and T2DM (rg = -0.172, p = 3 × 10-4). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p

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KW - Autism Spectrum Disorder/psychology

KW - Brain

KW - Depressive Disorder, Major/genetics

KW - Diabetes Mellitus, Type 2/genetics

KW - Genome-Wide Association Study

KW - Humans

KW - Insulin

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DO - 10.1038/s41398-022-01817-0

M3 - Journal article

C2 - 35165256

SN - 2158-3188

VL - 12

SP - 59

JO - Translational psychiatry

JF - Translational psychiatry

IS - 1

M1 - 59

ER -

Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders

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Keywords

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