Although survival rates for infants born extremely preterm (less than 28 weeks of pregnancy) had improved in recent decades, neurodevelopmental impairment remained a major issue. Children born severely preterm from early childhood to maturity were at substantial risk of cognitive impairment. However, there was little evidence of hereditary variables linked to cognitive impairment in the population. To begin, researchers employed a latent profile analysis (LPA) method to describe neurocognitive function in children born extremely preterm at the age of 10. The children were divided into 2 groups: those with no or minor cognitive impairment and those with moderate-to-severe cognitive impairment. Second, on samples with genotyping array data (n=528), investigators did TOPMed-based genotype imputation. Finally, for LPA-inferred cognitive impairment, they conducted a genome-wide association study (GWAS). Finally, computational analysis investigated the mechanisms behind the variation x LPA relationship. TEA domain transcription factor 4 (TEAD4 at rs11829294, P=2.40e-8) and syntaxin 18 (STX18 at rs79453226, P=1.91e-8) were shown to have genome-wide significance (P<5e-8). Tetraspanin 9 (TSPAN9) and protein arginine methyltransferase 8 (PRMT8) were putative functional genes underpinning the GWAS signal at the TEAD4 locus, according to an integrative using brain expression quantitative trait loci (eQTL), chromatin conformation, and epigenomic annotations. The study team combined genetics data with an LPA-inferred phenotype in a computational approach for the first time. The research revealed that rs11829294 and its LD partners might have played a function in gene regulation that affected neurocognitive impairment in very preterm babies.


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