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Published on: March 10, 2020
Case-control association study of congenital heart disease from a tertiary paediatric cardiac centre from North India
Prachi Kukshal1, Radha O Joshi2, Ajay Kumar3
1Sri Sathya Sai Sanjeevani Research Foundation, NH-2, Delhi-Mathura Highway, Baghola, Haryana, District Palwal, Pin- 121102, India. prachi7k@gmail.com.
Insights
This study investigated genetic factors in congenital heart diseases (CHDs) in North India. Certain Caucasian single nucleotide polymorphisms (SNPs) showed significant associations, suggesting shared genetic contributions to CHDs across populations.
Area of Science:
- Genetics
- Cardiology
- Pediatrics
Background:
- Congenital heart diseases (CHDs) represent a significant portion of birth defects, with complex and often elusive etiopathogenesis.
- Phenotypic variability in CHDs suggests gene-environment interactions, with genetic analyses indicating a multigenic basis.
- Limited genetic insights exist for CHDs in the Indian population, despite their high prevalence.
Purpose of the Study:
- To investigate the association of Caucasian single nucleotide polymorphisms (SNPs) with congenital heart diseases in a North Indian cohort.
- To explore potential shared genetic risk factors for CHDs between Caucasian and North Indian populations.
- To identify specific SNPs associated with different subtypes of CHDs.
Main Methods:
- A case-control study involving 306 CHD cases (198 acyanotic, 108 cyanotic) and controls from North India.
- Genotyping of 23 SNPs, previously identified through Genome-wide association studies (GWAS) in Caucasian populations, using Agena MassARRAY Technology.
- Statistical analysis to test for associations between SNPs and CHD phenotypes.
Main Results:
- Fifty percent of the studied SNPs demonstrated significant associations with CHD, either in allelic, genotypic, or sub-phenotype analyses.
- Strongest allelic associations were found for rs73118372 (CRELD1), rs28711516 (MYH6), and rs735712 (MYH7), with significant links to both acyanotic and cyanotic CHD.
- Specific SNPs, rs28711516 and rs735712, also showed genotypic associations, and rs735712 was most strongly associated with ventricular septal defects (VSD) and atrial septal defects (ASD).
Conclusions:
- Findings partially replicate Caucasian genetic associations in the North Indian population, indicating shared genetic underpinnings for CHDs.
- The results underscore the contribution of genetic factors, alongside environmental and sociodemographic influences, in CHD development.
- Further research in this population is warranted to elucidate the complex etiology of CHDs.
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.
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