Journal of Environmental Biology

Genetic architecture of childhood intelligence: A comprehensive analysis of GWAS-derived genes and their functional implications

S. Puthalapattu¹, P. Dinesh²*, E.V. Ravikanth³ and S. Vasishta⁴     

¹Department of Anaesthesiology, Apollo Institute of Medical Sciences and Research Chittoor, Murukambattu - 517 127, India

²Department of Psychiatry, Apollo Institute of Medical Sciences and Research Chittoor, Murukambattu - 517 1 27, India

³Department of Dermatology, Apollo Institute of Medical Sciences and Research Chittoor, Murukambattu - 517 127, India

⁴Department of Biochemistry, Apollo Institute of Medical Sciences and Research, Chittoor, Murukambattu - 517 127, India

Received: 29 November 2025                   Revised: 04 May 2026                   Accepted: 13 May 2026

*Corresponding Author Email: dinesh_p@aimsrchittoor.edu.in                  *ORCiD: https://orcid.org/0000-0001-8809-2197

Abstract

Aim: Childhood intelligence is a key neuro-developmental trait influencing the academic performance and broader life outcomes. Despite evidence of substantial heritability from twin and family studies, its underlying genetic framework remains incompletely characterised. This study examined the genes implicated in genome-wide association studies (GWAS) of intelligence and explored their functional relevance through integrative bioinformatic approaches.

Methodology: GWAS-implicated genes were subjected to layered bioinformatic analyses, encompassing gene ontology enrichment, pathway mapping, and protein–protein interaction (PPI) network assessment. Particular focus was directed towards KCNA1, KCNA5, LRPPRC, ESF1, RAPGEF2 and ABRA, given their recurrent appearance across studies and putative neurobiological relevance.

Results: Functional annotation revealed significant enrichment for potassium ion transport (p = 0.0012), voltage-gated potassium channel activity (p = 0.00055), and neuronal projection development (p = 0.0244). KCNA1 and KCNA5 mapped to voltage-gated potassium channel complexes, whilst RAPGEF2 showed associations with forebrain neuron differentiation and cAMP/cGMP signalling. LRPPRC was predominantly linked to mitochondrial processes and early developmental regulation.

Interpretation: These findings suggest childhood intelligence is shaped through coordinated regulation of neuronal excitability, intracellular signalling and developmental energy metabolism, offering molecular context for cognitive development and directions for future gene–environment interaction research.

Key words: Childhood intelligence, GWAS, Genetic pathways, Neurodevelopment, Potassium channels

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