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A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Author

Listed:
  • Xueyi Shen

    (University of Edinburgh)

  • David M. Howard

    (University of Edinburgh
    King’s College London)

  • Mark J. Adams

    (University of Edinburgh)

  • W. David Hill

    (University of Edinburgh
    University of Edinburgh)

  • Toni-Kim Clarke

    (University of Edinburgh)

  • Ian J. Deary

    (University of Edinburgh
    University of Edinburgh)

  • Heather C. Whalley

    (University of Edinburgh)

  • Andrew M. McIntosh

    (University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

Abstract

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR

Suggested Citation

  • Xueyi Shen & David M. Howard & Mark J. Adams & W. David Hill & Toni-Kim Clarke & Ian J. Deary & Heather C. Whalley & Andrew M. McIntosh, 2020. "A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16022-0
    DOI: 10.1038/s41467-020-16022-0
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    Cited by:

    1. Peter Zhukovsky & Earvin S. Tio & Gillian Coughlan & David A. Bennett & Yanling Wang & Timothy J. Hohman & Diego A. Pizzagalli & Benoit H. Mulsant & Aristotle N. Voineskos & Daniel Felsky, 2024. "Genetic influences on brain and cognitive health and their interactions with cardiovascular conditions and depression," Nature Communications, Nature, vol. 15(1), pages 1-11, 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. Weikang Gong & Yan Fu & Bang-Sheng Wu & Jingnan Du & Liu Yang & Ya-Ru Zhang & Shi-Dong Chen & JuJiao Kang & Ying Mao & Qiang Dong & Lan Tan & Jianfeng Feng & Wei Cheng & Jin-Tai Yu, 2024. "Whole-exome sequencing identifies protein-coding variants associated with brain iron in 29,828 individuals," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Guanghao Qi & Surya B. Chhetri & Debashree Ray & Diptavo Dutta & Alexis Battle & Samsiddhi Bhattacharjee & Nilanjan Chatterjee, 2024. "Genome-wide large-scale multi-trait analysis characterizes global patterns of pleiotropy and unique trait-specific variants," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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