Genome-scale copy number variant analysis in schizophrenia patients and controls from South India

Minali Singh; Dibyabhabha Pradhan; Poornima Kkani; Gundugurti Prasad Rao; Naveen Kumar Dhagudu; Lov Kumar; Chellamuthu Ramasubramanian; Srinivasan Ganesh Kumar; Surekha Sonttineni; Kommu Naga Mohan

doi:10.3389/fnmol.2023.1268827

Genome-scale copy number variant analysis in schizophrenia patients and controls from South India

Front Mol Neurosci. 2023 Dec 21:16:1268827. doi: 10.3389/fnmol.2023.1268827. eCollection 2023.

Affiliations

¹ Molecular Biology and Genetics Laboratory, Department of Biological Sciences, Birla Institute of Technology and Science, Pilani - Hyderabad Campus, Hyderabad, India.
² Centralized Core Research Facility, All India Institute of Medical Sciences, New Delhi, India.
³ Department of Zoology, Thiagarajar College, Madurai, India.
⁴ Asha Hospital Institute of Medical Psychology, Hyderabad, India.
⁵ ESIC Medical College and Hospital, Hyderabad, India.
⁶ Department of Computer Engineering, National Institute of Technology, Kurukshetra, India.
⁷ Department of Psychiatry, M.S. Chellamuthu Trust and Research Foundation, Madurai, India.
⁸ Centre for Human Disease Research, Birla Institute of Technology and Science, Pilani - Hyderabad Campus, Hyderabad, India.

Abstract

Copy number variants (CNVs) are among the main genetic factors identified in schizophrenia (SZ) through genome-scale studies conducted mostly in Caucasian populations. However, to date, there have been no genome-scale CNV reports on patients from India. To address this shortcoming, we generated, for the first time, genome-scale CNV data for 168 SZ patients and 168 controls from South India. In total, 63 different CNVs were identified in 56 patients and 46 controls with a significantly higher proportion of medium-sized deletions (100 kb-1 Mb) after multiple testing (FDR = 2.7E-4) in patients. Of these, 13 CNVs were previously reported; however, when searched against GWAS, transcriptome, exome, and DNA methylation studies, another 17 CNVs with candidate genes were identified. Of the total 30 CNVs, 28 were present in 38 patients and 12 in 27 controls, indicating a significantly higher representation in the former (p = 1.87E-5). Only 4q35.1-q35.2 duplications were significant (p = 0.020) and observed in 11 controls and 2 patients. Among the others that are not significant, a few examples of patient-specific and previously reported CNVs include deletions of 11q14.1 (DLG2), 22q11.21, and 14q21.1 (LRFN5). 16p13.3 deletion (RBFOX1), 3p14.2 duplication (CADPS), and 7p11.2 duplication (CCT6A) were some of the novel CNVs containing candidate genes. However, these observations need to be replicated in a larger sample size. In conclusion, this report constitutes an important foundation for future CNV studies in a relatively unexplored population. In addition, the data indicate that there are advantages in using an integrated approach for better identification of candidate CNVs for SZ and other mental health disorders.

Keywords: CNVs; India; PsychArray; case–control studies; deletions; duplications; schizophrenia.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was partially supported by grants from Department of Science and Technology (DST-India), Indian Council for Medical Research (ICMR-India), and Centre for Human Disease Research (CHDR) BITS-Pilaniand BITS Pilani Hyderabad Campus. MS was supported by fellowships from BITS Pilani and Indian Council of Medical Research.