RT Journal Article SR Electronic T1 Brain White Matter Development Is Associated with a Human-Specific Haplotype Increasing the Synthesis of Long Chain Fatty Acids JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6367 OP 6376 DO 10.1523/JNEUROSCI.2818-13.2014 VO 34 IS 18 A1 Bart D. Peters A1 Aristotle N. Voineskos A1 Philip R. Szeszko A1 Tristram A. Lett A1 Pamela DeRosse A1 Saurav Guha A1 Katherine H. Karlsgodt A1 Toshikazu Ikuta A1 Daniel Felsky A1 Majnu John A1 David J. Rotenberg A1 James L. Kennedy A1 Todd Lencz A1 Anil K. Malhotra YR 2014 UL http://www.jneurosci.org/content/34/18/6367.abstract AB The genetic and molecular pathways driving human brain white matter (WM) development are only beginning to be discovered. Long chain polyunsaturated fatty acids (LC-PUFAs) have been implicated in myelination in animal models and humans. The biosynthesis of LC-PUFAs is regulated by the fatty acid desaturase (FADS) genes, of which a human-specific haplotype is strongly associated with ω-3 and ω-6 LC-PUFA concentrations in blood. To investigate the relationship between LC-PUFA synthesis and human brain WM development, we examined whether this FADS haplotype is associated with age-related WM differences across the life span in healthy individuals 9–86 years of age (n = 207). Diffusion tensor imaging was performed to measure fractional anisotropy (FA), a putative measure of myelination, of the cerebral WM tracts. FADS haplotype status was determined with a single nucleotide polymorphism (rs174583) that tags this haplotype. Overall, normal age-related WM differences were observed, including higher FA values in early adulthood compared with childhood, followed by lower FA values across older age ranges. However, individuals homozygous for the minor allele (associated with lower LC-PUFA concentrations) did not display these normal age-related WM differences (significant age × genotype interactions, pcorrected < 0.05). These findings suggest that LC-PUFAs are involved in human brain WM development from childhood into adulthood. This haplotype and LC-PUFAs may play a role in myelin-related disorders of neurodevelopmental origin.