NDLI: Exploring the novel SNPs in neuroticism and birth weight based on GWAS datasets

Content Provider	Springer Nature : BioMed Central
Author	Zhou, Xiao-Ying Liu, Rui-Ke Zeng, Chun-Ping
Abstract	Objectives Epidemiological studies have confirmed that low birth weight (BW) is related to neuroticism and they may have a common genetic mechanism based on phenotypic correlation research. We conducted our study on a European population with 159,208 neuroticism and 289,142 birth weight samples. In this study, we aimed to identify new neuroticism single nucleotide polymorphisms (SNPs) and pleiotropic SNPs associated with neuroticism and BW and to provide more theoretical basis for the pathogenesis of the disease. Methods We estimated the pleiotropic enrichment between neuroticism and BW in two independent Genome-wide association studies (GWAS) when the statistical thresholds were Conditional False Discovery Rate (cFDR) < 0.01 and Conjunctional Conditional False Discovery Rate (ccFDR) < 0.05. We performed gene annotation and gene functional analysis on the selected significant SNPs to determine the biological role of gene function and pathogenesis. Two-sample Mendelian Randomization (TSMR) analysis was performed to explore the causal relationship between the neuroticism and BW. Results The conditional quantile–quantile plots (Q-Q plot) indicated that neuroticism and BW have strong genetic pleiotropy enrichment trends. With the threshold of cFDR < 0.001, we identified 126 SNPs related to neuroticism and 172 SNPs related to BW. With the threshold of ccFDR < 0.05, we identified 62 SNPs related to both neuroticism and BW. Among these SNPs, rs8039305 and rs35755513 have eQTL (expressed quantitative trait loci) and meQTL (methylation quantitative trait loci) effects simultaneously. Through GO enrichment analysis we also found that the two pathways of positive regulation of “mesenchymal cell proliferation” and “DNA-binding transcription factor activity” were significantly enriched in neuroticism and BW. Mendelian randomization analysis results indicate that there is no obvious causal relationship between neuroticism and birth weight. Conclusion We found 126 SNPs related to neuroticism, 172 SNPs related to BW and 62 SNPs associated with both neuroticism and BW, which provided a theoretical basis for their genetic mechanism and novel potential targets for treatment/intervention development.
Related Links	https://bmcmedgenomics.biomedcentral.com/counter/pdf/10.1186/s12920-023-01591-y.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	17558794
DOI	10.1186/s12920-023-01591-y
Journal	BMC Medical Genomics
Issue Number	1
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2023-07-15
Access Restriction	Open
Subject Keyword	Human Genetics Microarrays Gene Expression Neuroticism Birth weight Conditional FDR Genome-wide association study (GWAS)
Content Type	Text
Resource Type	Article
Subject	Genetics (clinical) Genetics
Journal Impact Factor	2.1/2023
5-Year Journal Impact Factor	2.5/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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