Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity

iPSYCH-Broad Consortium; Esben Agerbo; Anders D. Børglum; Ditte Demontis

doi:10.1038/s41598-022-26845-0

Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity

iPSYCH-Broad Consortium, Esben Agerbo, Anders D. Børglum, Ditte Demontis^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Cognitive functions of individuals with psychiatric disorders differ from that of the general population. Such cognitive differences often manifest early in life as differential school performance and have a strong genetic basis. Here we measured genetic predictors of school performance in 30,982 individuals in English, Danish and mathematics via a genome-wide association study (GWAS) and studied their relationship with risk for six major psychiatric disorders. When decomposing the school performance into math and language-specific performances, we observed phenotypically and genetically a strong negative correlation between math performance and risk for most psychiatric disorders. But language performance correlated positively with risk for certain disorders, especially schizophrenia, which we replicate in an independent sample (n = 4547). We also found that the genetic variants relating to increased risk for schizophrenia and better language performance are overrepresented in individuals involved in creative professions (n = 2953) compared to the general population (n = 164,622). The findings together suggest that language ability, creativity and psychopathology might stem from overlapping genetic roots.

Original language	English
Article number	429
Journal	Scientific Reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-26845-0
Publication status	Published - 9 Jan 2023

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@article{1167fcc01b194975b9d3d6210cf1af55,

title = "Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity",

abstract = "Cognitive functions of individuals with psychiatric disorders differ from that of the general population. Such cognitive differences often manifest early in life as differential school performance and have a strong genetic basis. Here we measured genetic predictors of school performance in 30,982 individuals in English, Danish and mathematics via a genome-wide association study (GWAS) and studied their relationship with risk for six major psychiatric disorders. When decomposing the school performance into math and language-specific performances, we observed phenotypically and genetically a strong negative correlation between math performance and risk for most psychiatric disorders. But language performance correlated positively with risk for certain disorders, especially schizophrenia, which we replicate in an independent sample (n = 4547). We also found that the genetic variants relating to increased risk for schizophrenia and better language performance are overrepresented in individuals involved in creative professions (n = 2953) compared to the general population (n = 164,622). The findings together suggest that language ability, creativity and psychopathology might stem from overlapping genetic roots.",

author = "Rajagopal, {Veera M.} and Andrea Ganna and Coleman, {Jonathan R.I.} and Andrea Allegrini and Georgios Voloudakis and Jakob Grove and Als, {Thomas D.} and Horsdal, {Henriette T.} and Liselotte Petersen and Vivek Appadurai and Andrew Schork and Alfonso Buil and Bulik, {Cynthia M.} and Jonas Bybjerg-Grauholm and Marie B{\ae}kvad-Hansen and Hougaard, {David M.} and Ole Mors and Merete Nordentoft and Thomas Werge and {iPSYCH-Broad Consortium} and Mortensen, {Preben Bo} and Gerome Breen and Panos Roussos and Robert Plomin and Esben Agerbo and B{\o}rglum, {Anders D.} and Ditte Demontis",

note = "Funding Information: (1) The iPSYCH project is funded by the Lundbeck Foundation (grant numbers R102-A9118 and R155-2014-1724) and the universities and university hospitals of Aarhus and Copenhagen. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. Data handling and analysis on the GenomeDK HPC facility was supported by NIMH (1U01MH109514-01 to Michael O{\textquoteright}Donovan and ADB). High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine, Aarhus University and Central Region Denmark, and Centre for Integrative Sequencing, iSEQ, Aarhus University (grant to ADB). (2) The Anorexia Nervosa Genetics Initiative (ANGI) was an initiative of the Klarman Family Foundation. (3) The PhD fellowship of V.M.R was fully funded by the Graduate School of Health, Aarhus University, Aarhus, Denmark. (4) G.V is supported by the Leon Levy Foundation (Leon Levy Fellowship in Neuroscience) and by NIH grant R01MH109677. (5) P.R is supported by the National Institutes of Health (R01AG050986 Roussos, R01MH109677 Roussos, U01MH116442 Roussos, R01MH110921 Roussos) and the Veterans Affairs (Merit grant BX004189 and BX002395 Roussos). (6) We gratefully acknowledge the ongoing contribution of the participants in the Twins Early Development Study (TEDS) and their families. TEDS is supported by a programme grant to RP from the UK Medical Research Council (MR/M021475/1 and previously G0901245), with additional support from the US National Institutes of Health (AG046938). The research leading to these results has also received funding from the European Research Council under the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007- 2013)/grant agreement n° 602768 and ERC grant agreement n° 295366. (7) R.P is supported by a Medical Research Council Professorship award (G19/2). This project has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 721567. (8) A.G.A. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie grant agreement no. 721567. (9) The authors acknowledge use of the research computing facility at King{\textquoteright}s College London, Rosalind ( https://rosalind.kcl.ac.uk ), which is delivered in partnership with the National Institute for Health Research (NIHR) Biomedical Research Centres at South London & Maudsley and Guy{\textquoteright}s & St. Thomas{\textquoteright} NHS Foundation Trusts, and part-funded by capital equipment grants from the Maudsley Charity (award 980) and Guy{\textquoteright}s & St. Thomas{\textquoteright} Charity (TR130505). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, King{\textquoteright}s College London, or the Department of Health and Social Care. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = jan,

day = "9",

doi = "10.1038/s41598-022-26845-0",

language = "English",

volume = "13",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity

AU - Rajagopal, Veera M.

AU - Ganna, Andrea

AU - Coleman, Jonathan R.I.

AU - Allegrini, Andrea

AU - Voloudakis, Georgios

AU - Grove, Jakob

AU - Als, Thomas D.

AU - Horsdal, Henriette T.

AU - Petersen, Liselotte

AU - Appadurai, Vivek

AU - Schork, Andrew

AU - Buil, Alfonso

AU - Bulik, Cynthia M.

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Hougaard, David M.

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - iPSYCH-Broad Consortium

AU - Mortensen, Preben Bo

AU - Breen, Gerome

AU - Roussos, Panos

AU - Plomin, Robert

AU - Agerbo, Esben

AU - Børglum, Anders D.

AU - Demontis, Ditte

N1 - Funding Information: (1) The iPSYCH project is funded by the Lundbeck Foundation (grant numbers R102-A9118 and R155-2014-1724) and the universities and university hospitals of Aarhus and Copenhagen. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. Data handling and analysis on the GenomeDK HPC facility was supported by NIMH (1U01MH109514-01 to Michael O’Donovan and ADB). High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine, Aarhus University and Central Region Denmark, and Centre for Integrative Sequencing, iSEQ, Aarhus University (grant to ADB). (2) The Anorexia Nervosa Genetics Initiative (ANGI) was an initiative of the Klarman Family Foundation. (3) The PhD fellowship of V.M.R was fully funded by the Graduate School of Health, Aarhus University, Aarhus, Denmark. (4) G.V is supported by the Leon Levy Foundation (Leon Levy Fellowship in Neuroscience) and by NIH grant R01MH109677. (5) P.R is supported by the National Institutes of Health (R01AG050986 Roussos, R01MH109677 Roussos, U01MH116442 Roussos, R01MH110921 Roussos) and the Veterans Affairs (Merit grant BX004189 and BX002395 Roussos). (6) We gratefully acknowledge the ongoing contribution of the participants in the Twins Early Development Study (TEDS) and their families. TEDS is supported by a programme grant to RP from the UK Medical Research Council (MR/M021475/1 and previously G0901245), with additional support from the US National Institutes of Health (AG046938). The research leading to these results has also received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007- 2013)/grant agreement n° 602768 and ERC grant agreement n° 295366. (7) R.P is supported by a Medical Research Council Professorship award (G19/2). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 721567. (8) A.G.A. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie grant agreement no. 721567. (9) The authors acknowledge use of the research computing facility at King’s College London, Rosalind ( https://rosalind.kcl.ac.uk ), which is delivered in partnership with the National Institute for Health Research (NIHR) Biomedical Research Centres at South London & Maudsley and Guy’s & St. Thomas’ NHS Foundation Trusts, and part-funded by capital equipment grants from the Maudsley Charity (award 980) and Guy’s & St. Thomas’ Charity (TR130505). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, King’s College London, or the Department of Health and Social Care. Publisher Copyright: © 2023, The Author(s).

PY - 2023/1/9

Y1 - 2023/1/9

N2 - Cognitive functions of individuals with psychiatric disorders differ from that of the general population. Such cognitive differences often manifest early in life as differential school performance and have a strong genetic basis. Here we measured genetic predictors of school performance in 30,982 individuals in English, Danish and mathematics via a genome-wide association study (GWAS) and studied their relationship with risk for six major psychiatric disorders. When decomposing the school performance into math and language-specific performances, we observed phenotypically and genetically a strong negative correlation between math performance and risk for most psychiatric disorders. But language performance correlated positively with risk for certain disorders, especially schizophrenia, which we replicate in an independent sample (n = 4547). We also found that the genetic variants relating to increased risk for schizophrenia and better language performance are overrepresented in individuals involved in creative professions (n = 2953) compared to the general population (n = 164,622). The findings together suggest that language ability, creativity and psychopathology might stem from overlapping genetic roots.

AB - Cognitive functions of individuals with psychiatric disorders differ from that of the general population. Such cognitive differences often manifest early in life as differential school performance and have a strong genetic basis. Here we measured genetic predictors of school performance in 30,982 individuals in English, Danish and mathematics via a genome-wide association study (GWAS) and studied their relationship with risk for six major psychiatric disorders. When decomposing the school performance into math and language-specific performances, we observed phenotypically and genetically a strong negative correlation between math performance and risk for most psychiatric disorders. But language performance correlated positively with risk for certain disorders, especially schizophrenia, which we replicate in an independent sample (n = 4547). We also found that the genetic variants relating to increased risk for schizophrenia and better language performance are overrepresented in individuals involved in creative professions (n = 2953) compared to the general population (n = 164,622). The findings together suggest that language ability, creativity and psychopathology might stem from overlapping genetic roots.

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U2 - 10.1038/s41598-022-26845-0

DO - 10.1038/s41598-022-26845-0

M3 - Article

C2 - 36624241

AN - SCOPUS:85145957547

SN - 2045-2322

VL - 13

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 429

ER -

Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity

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