IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34418-y.html
   My bibliography  Save this article

Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology

Author

Listed:
  • Max Lam

    (The Zucker Hillside Hospital, Northwell
    Feinstein Institutes for Medical Research
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Chia-Yen Chen

    (Translational Biology, Research and Development, Biogen Inc)

  • W. David Hill

    (University of Edinburgh)

  • Charley Xia

    (University of Edinburgh)

  • Ruoyu Tian

    (Computational Biology and Human Genetics, Dewpoint Therapeutics)

  • Daniel F. Levey

    (Yale University School of Medicine
    VA Connecticut Healthcare System)

  • Joel Gelernter

    (Yale University School of Medicine
    VA Connecticut Healthcare System
    Yale University School of Medicine
    Yale University School of Medicine)

  • Murray B. Stein

    (VA San Diego Healthcare System
    University of California, San Diego
    University of California San Diego)

  • Alexander S. Hatoum

    (Washington University in St. Louis Medical School)

  • Hailiang Huang

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Anil K. Malhotra

    (The Zucker Hillside Hospital, Northwell
    Feinstein Institutes for Medical Research
    Zucker School of Medicine at Hofstra/Norwell
    Zucker School of Medicine at Hofstra/Norwell)

  • Heiko Runz

    (Translational Biology, Research and Development, Biogen Inc)

  • Tian Ge

    (Broad Institute of MIT and Harvard
    Center for Genomic Medicine, Massachusetts General Hospital
    Massachusetts General Hospital, Harvard Medical School)

  • Todd Lencz

    (The Zucker Hillside Hospital, Northwell
    Feinstein Institutes for Medical Research
    Zucker School of Medicine at Hofstra/Norwell
    Zucker School of Medicine at Hofstra/Norwell)

Abstract

Cognitive deficits are known to be related to most forms of psychopathology. Here, we perform local genetic correlation analysis as a means of identifying independent segments of the genome that show biologically interpretable pleiotropic associations between cognitive dimensions and psychopathology. We identify collective segments of the genome, which we call “meta-loci”, showing differential pleiotropic patterns for psychopathology relative to either cognitive task performance (CTP) or performance on a non-cognitive factor (NCF) derived from educational attainment. We observe that neurodevelopmental gene sets expressed during the prenatal-early childhood period predominate in CTP-relevant meta-loci, while post-natal gene sets are more involved in NCF-relevant meta-loci. Further, we demonstrate that neurodevelopmental gene sets are dissociable across CTP meta-loci with respect to their spatial distribution across the brain. Additionally, we find that GABA-ergic, cholinergic, and glutamatergic genes drive pleiotropic relationships within dissociable meta-loci.

Suggested Citation

  • Max Lam & Chia-Yen Chen & W. David Hill & Charley Xia & Ruoyu Tian & Daniel F. Levey & Joel Gelernter & Murray B. Stein & Alexander S. Hatoum & Hailiang Huang & Anil K. Malhotra & Heiko Runz & Tian Ge, 2022. "Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34418-y
    DOI: 10.1038/s41467-022-34418-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34418-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-34418-y?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. Michael J. Hawrylycz & Ed S. Lein & Angela L. Guillozet-Bongaarts & Elaine H. Shen & Lydia Ng & Jeremy A. Miller & Louie N. van de Lagemaat & Kimberly A. Smith & Amanda Ebbert & Zackery L. Riley & Chr, 2012. "An anatomically comprehensive atlas of the adult human brain transcriptome," Nature, Nature, vol. 489(7416), pages 391-399, September.
    2. Alvaro N. Barbeira & Scott P. Dickinson & Rodrigo Bonazzola & Jiamao Zheng & Heather E. Wheeler & Jason M. Torres & Eric S. Torstenson & Kaanan P. Shah & Tzintzuni Garcia & Todd L. Edwards & Eli A. St, 2018. "Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics," Nature Communications, Nature, vol. 9(1), pages 1-20, December.
    3. Bates, Douglas & Mächler, Martin & Bolker, Ben & Walker, Steve, 2015. "Fitting Linear Mixed-Effects Models Using lme4," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 67(i01).
    4. Michael W. Dorrity & Lauren M. Saunders & Christine Queitsch & Stanley Fields & Cole Trapnell, 2020. "Dimensionality reduction by UMAP to visualize physical and genetic interactions," Nature Communications, Nature, vol. 11(1), pages 1-6, December.
    5. Lê, Sébastien & Josse, Julie & Husson, François, 2008. "FactoMineR: An R Package for Multivariate Analysis," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 25(i01).
    6. 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.
    7. Jeremy A. Miller & Song-Lin Ding & Susan M. Sunkin & Kimberly A. Smith & Lydia Ng & Aaron Szafer & Amanda Ebbert & Zackery L. Riley & Joshua J. Royall & Kaylynn Aiona & James M. Arnold & Crissa Bennet, 2014. "Transcriptional landscape of the prenatal human brain," Nature, Nature, vol. 508(7495), pages 199-206, April.
    8. Saori Sakaue & Jun Hirata & Masahiro Kanai & Ken Suzuki & Masato Akiyama & Chun Lai Too & Thurayya Arayssi & Mohammed Hammoudeh & Samar Al Emadi & Basel K. Masri & Hussein Halabi & Humeira Badsha & Im, 2020. "Dimensionality reduction reveals fine-scale structure in the Japanese population with consequences for polygenic risk prediction," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    9. 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.
    10. Vassily Trubetskoy & Antonio F. Pardiñas & Ting Qi & Georgia Panagiotaropoulou & Swapnil Awasthi & Tim B. Bigdeli & Julien Bryois & Chia-Yen Chen & Charlotte A. Dennison & Lynsey S. Hall & Max Lam & K, 2022. "Mapping genomic loci implicates genes and synaptic biology in schizophrenia," Nature, Nature, vol. 604(7906), pages 502-508, April.
    11. V. Bansal & M. Mitjans & C. A. P. Burik & R. K. Linnér & A. Okbay & C. A. Rietveld & M. Begemann & S. Bonn & S. Ripke & R. Vlaming & M. G. Nivard & H. Ehrenreich & P. D. Koellinger, 2018. "Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    12. Andrew D. Grotzinger & Mijke Rhemtulla & Ronald Vlaming & Stuart J. Ritchie & Travis T. Mallard & W. David Hill & Hill F. Ip & Riccardo E. Marioni & Andrew M. McIntosh & Ian J. Deary & Philipp D. Koel, 2019. "Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits," Nature Human Behaviour, Nature, vol. 3(5), pages 513-525, May.
    13. Ting Qi & Yang Wu & Jian Zeng & Futao Zhang & Angli Xue & Longda Jiang & Zhihong Zhu & Kathryn Kemper & Loic Yengo & Zhili Zheng & Riccardo E. Marioni & Grant W. Montgomery & Ian J. Deary & Naomi R. W, 2018. "Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    14. W. David Hill & Neil M. Davies & Stuart J. Ritchie & Nathan G. Skene & Julien Bryois & Steven Bell & Emanuele Di Angelantonio & David J. Roberts & Shen Xueyi & Gail Davies & David C. M. Liewald & Davi, 2019. "Genome-wide analysis identifies molecular systems and 149 genetic loci associated with income," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Mingyang Li & Xixi Dang & Yiwei Chen & Zhifan Chen & Xinyi Xu & Zhiyong Zhao & Dan Wu, 2024. "Cognitive processing speed and accuracy are intrinsically different in genetic architecture and brain phenotypes," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

    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. Gianmarco Mignogna & Caitlin E. Carey & Robbee Wedow & Nikolas Baya & Mattia Cordioli & Nicola Pirastu & Rino Bellocco & Kathryn Fiuza Malerbi & Michel G. Nivard & Benjamin M. Neale & Raymond K. Walte, 2023. "Patterns of item nonresponse behaviour to survey questionnaires are systematic and associated with genetic loci," Nature Human Behaviour, Nature, vol. 7(8), pages 1371-1387, August.
    2. Caitlin E. Carey & Rebecca Shafee & Robbee Wedow & Amanda Elliott & Duncan S. Palmer & John Compitello & Masahiro Kanai & Liam Abbott & Patrick Schultz & Konrad J. Karczewski & Samuel C. Bryant & Caro, 2024. "Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation," Nature Human Behaviour, Nature, vol. 8(8), pages 1599-1615, August.
    3. Yash Patel & Jean Shin & Eeva Sliz & Ariana Tang & Aniket Mishra & Rui Xia & Edith Hofer & Hema Sekhar Reddy Rajula & Ruiqi Wang & Frauke Beyer & Katrin Horn & Max Riedl & Jing Yu & Henry Völzke & Rob, 2024. "Genetic risk factors underlying white matter hyperintensities and cortical atrophy," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. 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.
    5. Mattia Marchi & Anne Alkema & Charley Xia & Chris H. L. Thio & Li-Yu Chen & Winni Schalkwijk & Gian M. Galeazzi & Silvia Ferrari & Luca Pingani & Hyeokmoon Kweon & Sara Evans-Lacko & W. David Hill & M, 2024. "Investigating the impact of poverty on mental illness in the UK Biobank using Mendelian randomization," Nature Human Behaviour, Nature, vol. 8(9), pages 1771-1783, September.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. Mingyang Li & Xixi Dang & Yiwei Chen & Zhifan Chen & Xinyi Xu & Zhiyong Zhao & Dan Wu, 2024. "Cognitive processing speed and accuracy are intrinsically different in genetic architecture and brain phenotypes," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    11. G. Ball & S. Oldham & V. Kyriakopoulou & L. Z. J. Williams & V. Karolis & A. Price & J. Hutter & M. L. Seal & A. Alexander-Bloch & J. V. Hajnal & A. D. Edwards & E. C. Robinson & J. Seidlitz, 2024. "Molecular signatures of cortical expansion in the human foetal brain," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    12. 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.
    13. Marika Vitali & Paolo Bosi & Elena Santacroce & Paolo Trevisi, 2021. "The multivariate approach identifies relationships between pre-slaughter factors, body lesions, ham defects and carcass traits in pigs," PLOS ONE, Public Library of Science, vol. 16(5), pages 1-14, May.
    14. Michael G. Levin & Noah L. Tsao & Pankhuri Singhal & Chang Liu & Ha My T. Vy & Ishan Paranjpe & Joshua D. Backman & Tiffany R. Bellomo & William P. Bone & Kiran J. Biddinger & Qin Hui & Ozan Dikilitas, 2022. "Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    15. Claire H Luby & Julie C Dawson & Irwin L Goldman, 2016. "Assessment and Accessibility of Phenotypic and Genotypic Diversity of Carrot (Daucus carota L. var. sativus) Cultivars Commercially Available in the United States," PLOS ONE, Public Library of Science, vol. 11(12), pages 1-19, December.
    16. Wendiao Zhang & Ming Zhang & Zhenhong Xu & Hongye Yan & Huimin Wang & Jiamei Jiang & Juan Wan & Beisha Tang & Chunyu Liu & Chao Chen & Qingtuan Meng, 2023. "Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    17. Annabelle Jade Bladon & Essam Yassin Mohammed & Belayet Hossain & Golam Kibria & Liaquat Ali & E J Milner-Gulland, 2018. "Evaluating the ecological and social targeting of a compensation scheme in Bangladesh," PLOS ONE, Public Library of Science, vol. 13(6), pages 1-19, June.
    18. Tingting Bo & Jie Li & Ganlu Hu & Ge Zhang & Wei Wang & Qian Lv & Shaoling Zhao & Junjie Ma & Meng Qin & Xiaohui Yao & Meiyun Wang & Guang-Zhong Wang & Zheng Wang, 2023. "Brain-wide and cell-specific transcriptomic insights into MRI-derived cortical morphology in macaque monkeys," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    19. Kristina M. Garske & Asha Kar & Caroline Comenho & Brunilda Balliu & David Z. Pan & Yash V. Bhagat & Gregory Rosenberg & Amogha Koka & Sankha Subhra Das & Zong Miao & Janet S. Sinsheimer & Jaakko Kapr, 2023. "Increased body mass index is linked to systemic inflammation through altered chromatin co-accessibility in human preadipocytes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    20. 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.

    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:13:y:2022:i:1:d:10.1038_s41467-022-34418-y. 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.