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, nā=ā1623) and long-term (LTM, nā=ā1522) 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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Supplementary Figure 1 Quantile-Quantile (Q-Q) plots of memory-related phenotypes. (a) Q-Q plot for STM measured in Digit Span task; (b) Q-Q plot for STM measured in Visuospatial memory task; (c) Q-Q plot for the shared component of STM measured in Digit Span task and in Visuospatial memory task; (d) Q-Q plot for LTM measurements. The red line represents null hypothesis. Blue dots represent results assuming an additive genetic model; orange dots represent results assuming a dominant/recessive genetic model. Plots were generated in R
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Zhu, Z., Chen, B., Yan, H. et al. Multi-level genomic analyses suggest new genetic variants involved in human memory. Eur J Hum Genet 26, 1668ā1678 (2018). https://doi.org/10.1038/s41431-018-0201-8
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DOI: https://doi.org/10.1038/s41431-018-0201-8
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