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Multi-level genomic analyses suggest new genetic variants involved in human memory

European Journal of Human Geneticsvolume 26pages16681678 (2018) | Download Citation

Abstract

Development of high-throughput genotyping platforms provides an opportunity to identify new genetic elements related to complex cognitive functions. Taking advantage of multi-level genomic analysis, here we studied the genetic basis of human short-term (STM, n = 1623) and long-term (LTM, n = 1522) memory functions. Heritability estimation based on single nucleotide polymorphism showed moderate (61%, standard error 35%) heritability of short-term memory but almost zero heritability of long-term memory. We further performed a two-step genome-wide association study, but failed to find any SNPs that could pass genome-wide significance and survive replication at the same time. However, suggestive significance for rs7011450 was found in the shared component of the two STM tasks. Further inspections on its nearby gene zinc finger and at-hook domain containing and SNPs around this gene showed suggestive association with STM. In LTM, a polymorphism within branched chain amino acid transaminase 2 showed suggestive significance in the discovery cohort and has been replicated in another independent population of 1862. Furthermore, we performed a pathway analysis based on the current genomic data and found pathways including mTOR signaling and axon guidance significantly associated with STM capacity. These findings warrant further replication in other larger populations.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Project 31421003); the Beijing Innovation Center for Genomics at Peking University; the Applied Development Program from the Science and Technology Committee of Chongqing (cstc2014yykfB10003 and cstc2015shms-ztzx10006); and the Program of Mass Creativities Workshops from the Science and Technology Committee of Chongqing. We are grateful to Zhangyan Guan and Huizhen Yang for help with DNA preparation. Zijian Zhu thanks the Chinese Scholarship Council (CSC, No. 201709920075) and the German Academic Research Foundation (DAAD, No. 91658524) for financial support.

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Author notes

  1. These authors contributed equally: Zijian Zhu, Biqing Chen.

  2. These authors jointly supervised this work: Zijian Zhu, Biqing Chen.

Affiliations

  1. PKU-IDG/McGovern Institute for Brain Research, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Beijing Innovation Center for Genomics, Peking University, 100871, Beijing, China

    • Zijian Zhu
    • , Biqing Chen
    • , Hongming Yan
    • , Wan Fang
    • , Wenxia Zhang
    •  & Yi Rao
  2. Central Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, 210029, Nanjing, China

    • Biqing Chen
  3. College of Laboratory Medicine, Chongqing Medical University, 400016, Chongqing, China

    • Qin Zhou
    • , Han Lei
    • , Ailong Huang
    •  & Tingmei Chen
  4. University-Town Hospital of Chongqing Medical University, 401331, Chongqing, China

    • Shanbi Zhou
  5. State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, 510515, Guangzhou, China

    • Tianming Gao
  6. Biostime institute of nutrition and care, 510623, Guangzhou, China

    • Liang Chen
  7. School of Traditional Chinese Medicine, Southern Medical University, 510515, Guangzhou, China

    • Jieyu Chen
  8. Division of Molecular Nephrology and Creative Training Center for Undergraduates, M.O.E. Key Laboratory of Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, 400016, Chongqing, China

    • Dongsheng Ni
    • , Yuping Gu
    •  & Jianing Liu

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The authors declare that they have no conflict of interest.

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Correspondence to Zijian Zhu or Biqing Chen.

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DOI

https://doi.org/10.1038/s41431-018-0201-8