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. 2023 Jun 15;23(1):290.
doi: 10.1186/s12887-023-04095-x.

Case-control association study of congenital heart disease from a tertiary paediatric cardiac centre from North India

Prachi Kukshal  1 , Radha O Joshi  2 , Ajay Kumar  3 , Shadab Ahamad  3 , Prabhatha Rashmi Murthy  4 , Yogesh Sathe  5 , Krishna Manohar  5 , Soma Guhathakurta  3 , Subramanian Chellappan  6
Affiliations

Case-control association study of congenital heart disease from a tertiary paediatric cardiac centre from North India

Prachi Kukshal et al. BMC Pediatr. .

Abstract

Background: Congenital Heart diseases (CHDs) account for 1/3rd of all congenital birth defects. Etiopathogenesis of CHDs remain elusive despite extensive investigations globally. Phenotypic heterogeneity witnessed in this developmental disorder reiterate gene-environment interactions with periconceptional factors as risk conferring; and genetic analysis of both sporadic and familial forms of CHD suggest its multigenic basis. Significant association of de novo and inherited variants have been observed. Approximately 1/5th of CHDs are documented in the ethnically distinct Indian population but genetic insights have been very limited. This pilot case-control based association study was undertaken to investigate the status of Caucasian SNPs in a north Indian cohort.

Method: A total of 306 CHD cases sub-classified into n = 198 acyanotic and n = 108 cyanotic types were recruited from a dedicated tertiary paediatric cardiac centre in Palwal, Haryana. 23 SNPs primarily prioritized from Genome-wide association studies (GWAS) on Caucasians were genotyped using Agena MassARRAY Technology and test of association was performed with adequately numbered controls.

Results: Fifty percent of the studied SNPs were substantially associated in either allelic, genotypic or sub-phenotype categories validating their strong correlation with disease manifestation. Of note, strongest allelic association was observed for rs73118372 in CRELD1 (p < 0.0001) on Chr3, rs28711516 in MYH6 (p = 0.00083) and rs735712 in MYH7 (p = 0.0009) both on Chr 14 and were also significantly associated with acyanotic, and cyanotic categories separately. rs28711516 (p = 0.003) and rs735712 (p = 0.002) also showed genotypic association. Strongest association was observed with rs735712(p = 0.003) in VSD and maximum association was observed for ASD sub-phenotypes.

Conclusions: Caucasian findings were partly replicated in the north Indian population. The findings suggest the contribution of genetic, environmental and sociodemographic factors, warranting continued investigations in this study population.

Keywords: Case–control association; Congenital Heart Disease; GWAS variants; North India.

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Conflict of interest statement

The Authors have no potential competing interests to declare.

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