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Identification of putative genetic variants in major depressive disorder patients in Pakistan

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Abstract

Background

Major depressive disorder (MDD) is a polygenic, and highly prevalent disorder affecting 322 million people globally. It results in several psychological changes which adversely affect different dimensions of life and may lead to suicide.

Methods

Whole exome sequencing of 15 MDD patients, enrolled at the Dr. A. Q. Khan Institute of Behavioral Sciences, Karachi, was performed using NextSeq500. Different bioinformatics tools and databases like ANNOVAR, ALoFT, and GWAS were used to identify both common and rare variants associated with the pathogenesis of MDD.

Results

A total of 1985 variations were identified in 479 MDD-related genes. Several SNPs including rs1079610, rs11750538, rs1799913, rs1801131, rs2230267, rs2231187, rs3819976, rs4314963, rs56265970, rs587780434, rs6330, rs75111588, rs7596487, and rs9624909 were prioritized due to their deleteriousness and frequency difference between the patients and the South Asian population. A non-synonymous variation rs56265970 (BCR) had 26% frequency in patients and was not found in the South Asian population; a multiallelic UTR-5′ insertion rs587780434 (RELN) was present with an allelic frequency of 70% in patients whereas 22% in the SAS population. Genetic alterations in PABPC1 genes, a stress-associated gene also had higher allele frequency in the cases than in the normal population.

Conclusion

This present study identifies both common and rare variants in the genes associated with the pathogenesis of MDD in Pakistani patients. Genetic variations in BCR, RELN, and stress-associated PABPC1 suggest potential roles in the pathogenesis of MDD.

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Data availability

The raw data that support the findings of this study has been deposited in the NCBI SRA archive under the BioProject PRJNA774142.

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Acknowledgements

We would like to extend our special gratitude to the medical staff and authorities of Dr. Abdul Qadir Khan Institute of Behavioral Sciences, Karachi for permitting us to collect blood samples on their premises.

Funding

The study was performed with the funding provided by The Searle Company Limited (TSCL), Karachi, Pakistan to the institute (Research Project ID 8211).

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Author notes

  1. Sarah Rizwan Qazi and Muhammad Irfan have contributed equally to this study.

Authors and Affiliations

  1. Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan

    Sarah Rizwan Qazi, Muhammad Irfan, Muhammad Jahanzaib, Maleeha Zaman Khan, Mahrukh Nasir, Muhammad Shakeel & Ishtiaq Ahmad Khan

  2. Dr. A. Q. Khan Institute of Behavioral Sciences, Dow University of Health Sciences, Karachi, 75280, Pakistan

    Zoobia Ramzan

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  1. Sarah Rizwan Qazi
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Correspondence to Ishtiaq Ahmad Khan.

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The procedures performed in this study involving human participants were in accordance with the Institutional Ethical Committee (Study accession number IEC-046-HB-2019), and with the 1964 Helsinki declaration and its later amendments.

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Qazi, S.R., Irfan, M., Ramzan, Z. et al. Identification of putative genetic variants in major depressive disorder patients in Pakistan. Mol Biol Rep 49, 2283–2292 (2022). https://doi.org/10.1007/s11033-021-07050-0

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