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The association between DNA methylation and human height and a prospective model of DNA methylation-based height prediction

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Abstract

As a vital anthropometric characteristic, human height information not only helps to understand overall developmental status and genetic risk factors, but is also important for forensic DNA phenotyping. We utilized linear regression analysis to test the association between each CpG probe and the height phenotype. Next, we designed a methylation sequencing panel targeting 959 CpGs and subsequent height inference models were constructed for the Chinese population. A total of 11,730 height-associated sites were identified. By employing KPCA and deep neural networks, a prediction model was developed, of which the cross-validation RMSE, MAE and R2 were 5.62 cm, 4.45 cm and 0.64, respectively. Genetic factors could explain 39.4% of the methylation level variance of sites used in the height inference models. Collectively, we demonstrated an association between height and DNA methylation status through an EWAS analysis. Targeted methylation sequencing of only 959 CpGs combined with deep learning techniques could provide a model to estimate human height with higher accuracy than SNP-based prediction models.

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Data availability

The raw sequence data generated in this study have been submitted to the Genome Sequence Archive in National Genomics Data Center, China National Center for Bioinformation / Beijing Institute of Genomics, Chinese Academy of Sciences (GSA-Human; https://ngdc.cncb.ac.cn/gsa-human) under accession number HRA004165.

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Acknowledgements

We thank Dr. Sarah Voisin for providing height information of the participants within their study (GEO Accession GSE73103). The authors would like to express their gratitude to EditSprings for the expert linguistic services provided. This work was supported by the National Natural Science Foundation of China (82072118); the S&T Program of Hebei (225A5602D); and the Natural Science Foundation of Hebei Province (H2021206451).

Funding

This work was supported by the National Natural Science Foundation of China (82072118); the S&T Program of Hebei (225A5602D); and the Natural Science Foundation of Hebei Province (H2021206451).

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Authors and Affiliations

  1. College of Forensic Medicine, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Hebei Medical University, Chinese Academy of Medical Sciences, Shijiazhuang, 050017, Hebei, China

    Zhonghua Wang, Guangping Fu, Guanju Ma, Qian Wang, Chaolong Lu, Lihong Fu, Xiaojing Zhang, Bin Cong & Shujin Li

  2. Physical Examination Center of Shijiazhuang People’s Hospital, Shijiazhuang, 050011, Hebei, China

    Chunyan Wang

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  1. Zhonghua Wang
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Contributions

Zhonghua Wang, Bin Cong and Shujin Li designed research; Zhonghua Wang, Guangping Fu, Guanju Ma, Qian Wang, Chaolong Lu and Lihong Fu performed research; Chunyan Wwang collected blood samples; Zhonghua Wang analyzed data; Zhonghua Wang and Shujin Li wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Shujin Li.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Medical Ethics Committee of Hebei Medical University (No. 20190013).

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Wang, Z., Fu, G., Ma, G. et al. The association between DNA methylation and human height and a prospective model of DNA methylation-based height prediction. Hum. Genet. 143, 401–421 (2024). https://doi.org/10.1007/s00439-024-02659-0

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  • DOI: https://doi.org/10.1007/s00439-024-02659-0

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