ABSTRACT
A better understanding of genetic influences on early white matter development could significantly advance our understanding of neurological and psychiatric conditions characterized by altered integrity of axonal pathways. We conducted a genome-wide association study (GWAS) of diffusion tensor imaging (DTI) phenotypes in 471 neonates. We used a hierarchical functional principal regression model (HFPRM) to perform joint analysis of 44 fiber bundles. HFPRM revealed a latent measure of white matter microstructure that explained approximately 50% of variation in our tractography-based measures and accounted for a large proportion of heritable variation in each individual bundle. An intronic SNP in PSMF1 on chromosome 20 exceeded the conventional GWAS threshold of 5 x 10-8 (p = 4.61 x 10-8). Additional loci nearing genome-wide significance were located near genes with known roles in axon growth and guidance, fasciculation, and myelination.
Subject(s)
Genome-Wide Association Study , White Matter/ultrastructure , Axons/physiology , Chromosomes, Human, Pair 20/genetics , Diffusion Magnetic Resonance Imaging , Diffusion Tensor Imaging , Female , Humans , Image Processing, Computer-Assisted , Infant , Infant, Newborn , Male , Myelin Sheath/physiology , Nerve Fibers/physiology , Phenotype , Polymorphism, Single Nucleotide , Proteasome Endopeptidase Complex/genetics , Regression AnalysisABSTRACT
Three series of experiments were carried out. Each experiment consisted of six or seven tests where four or five containers were fitted with thermocouples and five were fitted with biological indicator units (BIU). The sterilization value (F0) delivered to cans of peas in brine was calculated from heat penetration data. The heat penetration data were analyzed for test-to-test reproducibility within each experimental series. Sterilization values for all tests were calculated from the BIU test results. The sterilizing values F0 (PHY) determined from physical (PHY) heat penetration data were compared with sterilizing values F0 (BIO) determined using the BIUs, both on the basis of accuracy and variability. The mean F0 (PHY) - F0 (BIO) was + 1.2 min. The mean coefficient of variation of the F0 (PHY) was 0.03 and the F (BIO) was 0.06.
