The tangential growth of the human visual cortex and maternal smoking during pregnancy.

Exposure to maternal cigarette smoking in utero is a prenatal adversity due, in part, to the pharmacological effects of nicotine. During gestation, thalamocortical inputs-generated by cholinergic retinal waves-contribute to the development of the visual cortex (V1). First, we investigated the relationship between prenatal exposure to maternal cigarette smoking (PEMCS) and the tangential growth of V1. We observed a robust association between PEMCS and V1 surface area in the UK Biobank (n = 26,987 adults, 30% exposed) and replicated this relationship in the Saguenay Youth Study (n = 944 adolescents, 47% exposed). Subsequent in silico analyses suggested that PEMCS may influence V1 prenatal growth by disrupting the proliferation of intermediate progenitor cells and inhibitory neurons. Second, we explored the role of cholinergic retinal waves as a mechanistic pathway underlying this exposure-outcome relationship. To do so, we used causal variants in genes sensitive to retinal waves (identified in retinal ganglion cells). These variants were related to V1 surface area only among exposed individuals; deletions in these genes and putative loss-of-function single-nucleotide variants were associated with lower V1 surface area. These results suggest that PEMCS influences the prenatal tangential growth of the human V1 via the retina.