IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26755-1.html
   My bibliography  Save this article

Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy

Author

Listed:
  • Ellen Verhoef

    (Max Planck Institute for Psycholinguistics
    International Max Planck Research School for Language Sciences)

  • Jakob Grove

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    iSEQ, Aarhus University
    Center for Genomics and Personalized Medicine
    Aarhus University)

  • Chin Yang Shapland

    (University of Bristol
    University of Bristol)

  • Ditte Demontis

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    iSEQ, Aarhus University
    Center for Genomics and Personalized Medicine)

  • Stephen Burgess

    (University of Cambridge
    University of Cambridge)

  • Dheeraj Rai

    (University of Bristol
    University of Bristol
    Avon and Wiltshire Partnership NHS Mental Health Trust)

  • Anders D. Børglum

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    iSEQ, Aarhus University
    Center for Genomics and Personalized Medicine)

  • Beate St Pourcain

    (Max Planck Institute for Psycholinguistics
    University of Bristol
    Radboud University)

Abstract

Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are complex co-occurring neurodevelopmental conditions. Their genetic architectures reveal striking similarities but also differences, including strong, discordant polygenic associations with educational attainment (EA). To study genetic mechanisms that present as ASD-related positive and ADHD-related negative genetic correlations with EA, we carry out multivariable regression analyses using genome-wide summary statistics (N = 10,610–766,345). Our results show that EA-related genetic variation is shared across ASD and ADHD architectures, involving identical marker alleles. However, the polygenic association profile with EA, across shared marker alleles, is discordant for ASD versus ADHD risk, indicating independent effects. At the single-variant level, our results suggest either biological pleiotropy or co-localisation of different risk variants, implicating MIR19A/19B microRNA mechanisms. At the polygenic level, they point to a polygenic form of pleiotropy that contributes to the detectable genome-wide correlation between ASD and ADHD and is consistent with effect cancellation across EA-related regions.

Suggested Citation

  • Ellen Verhoef & Jakob Grove & Chin Yang Shapland & Ditte Demontis & Stephen Burgess & Dheeraj Rai & Anders D. Børglum & Beate St Pourcain, 2021. "Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26755-1
    DOI: 10.1038/s41467-021-26755-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26755-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-26755-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Christiaan A de Leeuw & Joris M Mooij & Tom Heskes & Danielle Posthuma, 2015. "MAGMA: Generalized Gene-Set Analysis of GWAS Data," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-19, April.
    2. Lorraine Southam & Arthur Gilly & Dániel Süveges & Aliki-Eleni Farmaki & Jeremy Schwartzentruber & Ioanna Tachmazidou & Angela Matchan & Nigel W. Rayner & Emmanouil Tsafantakis & Maria Karaleftheri & , 2017. "Whole genome sequencing and imputation in isolated populations identify genetic associations with medically-relevant complex traits," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    3. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Shahram Bahrami & Kaja Nordengen & Jaroslav Rokicki & Alexey A. Shadrin & Zillur Rahman & Olav B. Smeland & Piotr P. Jaholkowski & Nadine Parker & Pravesh Parekh & Kevin S. O’Connell & Torbjørn Elvsås, 2024. "The genetic landscape of basal ganglia and implications for common brain disorders," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Eva-Maria Stauffer & Richard A. I. Bethlehem & Lena Dorfschmidt & Hyejung Won & Varun Warrier & Edward T. Bullmore, 2023. "The genetic relationships between brain structure and schizophrenia," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Xiaofeng Zhu & Yihe Yang & Noah Lorincz-Comi & Gen Li & Amy R. Bentley & Paul S. de Vries & Michael Brown & Alanna C. Morrison & Charles N. Rotimi & W. James Gauderman & Dabeeru C. Rao & Hugues Aschar, 2024. "An approach to identify gene-environment interactions and reveal new biological insight in complex traits," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Sophie A. Riesmeijer & Zoha Kamali & Michael Ng & Dmitriy Drichel & Bram Piersma & Kerstin Becker & Thomas B. Layton & Jagdeep Nanchahal & Michael Nothnagel & Ahmad Vaez & Hans Christian Hennies & Pau, 2024. "A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren’s disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Zhiqiang Sha & Dick Schijven & Amaia Carrion-Castillo & Marc Joliot & Bernard Mazoyer & Simon E. Fisher & Fabrice Crivello & Clyde Francks, 2021. "The genetic architecture of structural left–right asymmetry of the human brain," Nature Human Behaviour, Nature, vol. 5(9), pages 1226-1239, September.
    6. Qiao Fan & Hengtong Li & Xiaomeng Wang & Yih-Chung Tham & Kelvin Yi Chong Teo & Masayuki Yasuda & Weng Khong Lim & Yuet Ping Kwan & Jing Xian Teo & Ching-Jou Chen & Li Jia Chen & Jeeyun Ahn & Sonia Da, 2023. "Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    7. Catherine M. Francis & Matthias E. Futschik & Jian Huang & Wenjia Bai & Muralidharan Sargurupremraj & Alexander Teumer & Monique M. B. Breteler & Enrico Petretto & Amanda S. R. Ho & Philippe Amouyel &, 2022. "Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    8. Palwende Romuald Boua & Jean-Tristan Brandenburg & Ananyo Choudhury & Hermann Sorgho & Engelbert A. Nonterah & Godfred Agongo & Gershim Asiki & Lisa Micklesfield & Solomon Choma & Francesc Xavier Góme, 2022. "Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    9. Sarah Grosche & Ingo Marenholz & Jorge Esparza-Gordillo & Aleix Arnau-Soler & Erola Pairo-Castineira & Franz Rüschendorf & Tarunveer S. Ahluwalia & Catarina Almqvist & Andreas Arnold & Hansjörg Baurec, 2021. "Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    10. Richard Burns & William J. Young & Nay Aung & Luis R. Lopes & Perry M. Elliott & Petros Syrris & Roberto Barriales-Villa & Catrin Sohrabi & Steffen E. Petersen & Julia Ramírez & Alistair Young & Patri, 2024. "Genetic basis of right and left ventricular heart shape," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    11. Ville Salo & Juhani Määttä & Eeva Sliz & Ene Reimann & Reedik Mägi & Kadri Reis & Abdelrahman G. Elhanas & Anu Reigo & Priit Palta & Tõnu Esko & Jaro Karppinen & Johannes Kettunen, 2024. "Genome-wide meta-analysis conducted in three large biobanks expands the genetic landscape of lumbar disc herniations," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    12. Hung-Lin Chen & Hsiu-Yin Chiang & David Ray Chang & Chi-Fung Cheng & Charles C. N. Wang & Tzu-Pin Lu & Chien-Yueh Lee & Amrita Chattopadhyay & Yu-Ting Lin & Che-Chen Lin & Pei-Tzu Yu & Chien-Fong Huan, 2024. "Discovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    13. Yu Huang & Denis Plotnikov & Huan Wang & Danli Shi & Cong Li & Xueli Zhang & Xiayin Zhang & Shulin Tang & Xianwen Shang & Yijun Hu & Honghua Yu & Hongyang Zhang & Jeremy A. Guggenheim & Mingguang He, 2024. "GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    14. Chun Chieh Fan & Robert Loughnan & Carolina Makowski & Diliana Pecheva & Chi-Hua Chen & Donald J. Hagler & Wesley K. Thompson & Nadine Parker & Dennis van der Meer & Oleksandr Frei & Ole A. Andreassen, 2022. "Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    15. Charley Xia & Sarah J. Pickett & David C. M. Liewald & Alexander Weiss & Gavin Hudson & W. David Hill, 2023. "The contributions of mitochondrial and nuclear mitochondrial genetic variation to neuroticism," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Dennis Meer & Oleksandr Frei & Tobias Kaufmann & Alexey A. Shadrin & Anna Devor & Olav B. Smeland & Wesley K. Thompson & Chun Chieh Fan & Dominic Holland & Lars T. Westlye & Ole A. Andreassen & Anders, 2020. "Understanding the genetic determinants of the brain with MOSTest," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    17. Tzu-Ting Chen & Jaeyoung Kim & Max Lam & Yi-Fang Chuang & Yen-Ling Chiu & Shu-Chin Lin & Sang-Hyuk Jung & Beomsu Kim & Soyeon Kim & Chamlee Cho & Injeong Shim & Sanghyeon Park & Yeeun Ahn & Aysu Okbay, 2024. "Shared genetic architectures of educational attainment in East Asian and European populations," Nature Human Behaviour, Nature, vol. 8(3), pages 562-575, March.
    18. William R. Reay & Michael P. Geaghan & Murray J. Cairns, 2022. "The genetic architecture of pneumonia susceptibility implicates mucin biology and a relationship with psychiatric illness," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    19. Nagel, Mats, 2020. "Changing perspectives: Towards detailed phenotyping in genetics," Thesis Commons a4nz2, Center for Open Science.
    20. Rebecca Shafee & Dustin Moraczewski & Siyuan Liu & Travis Mallard & Adam Thomas & Armin Raznahan, 2024. "A sex-stratified analysis of the genetic architecture of human brain anatomy," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26755-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.