Effects of DISC1 and hypoxia-sensitive genes on dermatoglyphics and cognitive function in schizophrenia

Dermatoglyphics are considered neurodevelopmental markers due to their shared ectodermal origin with the central nervous system. After birth, dermatoglyphics remain unchanged, as stable indicators of genetic and environmental influences shaping early development. Their simplification, disruption, or asymmetry has been associated with schizophrenia (SZ) risk. Polymorphic variability at DISC1 and other prenatal risk-sensitive genes has also been linked to SZ. This study investigated the influence of DISC1 and other hypoxia-related genes on SZ risk through a family-based analysis of dermatoglyphic and cognitive markers. The sample included 61 nuclear families with one offspring diagnosed with SZ-spectrum disorders (n = 208). The dermatoglyphic variables assessed were: finger pattern intensity (PII), total a-b ridge count (TABRC) and its fluctuating asymmetry (FA_ABRC), ATD angle and dissociations. Five single nucleotide polymorphisms were genotyped at DISC1 and 18 at DISC1-interactome genes (AKT1, BDNF, COMT, NOS1AP, and RGS4), linked to SZ and hypoxia response. We analysed intrafamily transmission of genetic variants with dermatoglyphic variables and their effect on cognition. Our analyses showed that DISC1-rs999710 allelic variability is co-transmitted with dermatoglyphic markers previously associated with neurodevelopment deviances (lower PII and wider ATD angle) to the affected offspring, and that other genes (BDNF, NOS1AP and RGS4) contribute additively to these effects. Also, our data indicate a link between less complex finger patterns and poorer memory performance, while the DISC1-rs999710 and RGS4-rs10917670 combination relates to lower attention scores. These findings highlight the role of DISC1 in dermatoglyphic trait transmission in SZ and the additive effects of interacting hypoxia-related genes, underscoring neurodevelopmental markers' relevance in SZ and cognition.