Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men.Peer reviewe

Identification of NCAN as a candidate gene for developmental dyslexia

A whole-genome linkage analysis in a Finnish pedigree of eight cases with developmental dyslexia (DD) revealed several regions shared by the affected individuals. Analysis of coding variants from two affected individuals identified rs146011974G >A (Ala1039Thr), a rare variant within the NCAN gene co-segregating with DD in the pedigree. This variant prompted us to consider this gene as a putative candidate for DD. The RNA expression pattern of the NCAN gene in human tissues was highly correlated (R > 0.8) with that of the previously suggested DD susceptibility genes KIAA0319, CTNND2, CNTNAP2 and GRIN2B. We investigated the association of common variation in NCAN to brain structures in two data sets: young adults (Brainchild study, Sweden) and infants (FinnBrain study, Finland). In young adults, we found associations between a common genetic variant in NCAN, rs1064395, and white matter volume in the left and right temporoparietal as well as the left inferior frontal brain regions. In infants, this same variant was found to be associated with cingulate and prefrontal grey matter volumes. Our results suggest NCAN as a new candidate gene for DD and indicate that NCAN variants affect brain structure.Peer reviewe