Genome-wide profiling and identification of Single Nucleotide Polymorphisms (SNPs) relevant to susceptibility to neurodevelopmental disorders
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Institute for Maternal and Child health IRCCS “Burlo Garofolo”, Trieste, Italy
Publication date: 2021-09-27
Public Health Toxicol 2021;1(Supplement 1):A61
The research is based on the study of the interplay between genetic variability and co-exposure to chemicals for extended period of time and how this contributes to the development or exacerbation of central nervous system disorders during child development. Identification of single nucleotide polymorphisms (SNPs) may help predict an individual’s susceptibility to environmental pollutants, and the risk of onset of neurodevelopmental disorders. Genome-wide association studies (GWASs) have identified a large number of genetic variants, significantly associated with a wide range of complex traits. However, these variants typically have a small effect and correspond to a small fraction of truly associated variants, meaning that they have limited predictive power. Therefore, our approach to this constraint is the polygenic risk score (PRS) application which is an estimate of an individual’s genetic liability to a trait or disease, calculated according to their genotype profile and relevant GWAS data.

Cord blood/tissue and saliva samples from the Italian (604 samples), Slovenian (249 samples) and Croatian (149 samples) PHIME cohorts were collected for DNA extraction. All samples (total 1002) were genotyped with Infinium Global Screening arrays by Illumina (Illumina Inc., San Diego, CA, USA). Genotype imputation was followed in order to estimate missing genotypes from the genotype reference panel. Reference data were obtained from a GWAS meta-analysis, in 269,867 individuals which identifies new genetic and functional links to intelligence. Both reference data and our PHIME target data underwent quality control using Genome studio, plink and R software, where SNPs and individuals were removed due to mismatching, duplicate and ambiguous SNPs or sample overlap and relatedness. Using a linear mixed model in the genome-wide complex trait analysis software, PRSice-2, PRS analysis was applied on the remaining samples (983 individuals), in order to explain the heritability of children cognitive scores at 18 months of age by evaluating the effects of all SNPs simultaneously.

Cognitive scores of 983 children were normally distributed and the value range was from 70 to 145. A multiple linear regression model was applied to find the relationship between children cognitive scores and a variety of explanatory variables. Statistically significant associations were found between cognitive scores and PRS scores (p=0.000212), maternal age at delivery (p=0.000640) and child fresh and homogenized fish intake, p=0.016357 and p=0.07626, respectively. While, no association was found between cognitive scores and THg cord blood levels, maternal BMI, maternal alcohol consumption, child birthweight and birth length (p>0.05).

We found some evidence that the health outcome of our study is directly associated with the genotype profile and can be adversely influenced by the maternal age as well as, by child fish consumption.