For a study, the researchers sought to advance the general analytic framework by developing new methods in application to XYY syndrome—a sex chromosome aneuploidy known to increase the risk for psychopathology. The researchers further, analyzed a range of cognitive and behavioral domains in XYY probands and their non-carrier family members (n=58 families), including the general cognitive ability (FSIQ), as well as continuous measures of traits associated with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Proband scores were shifted from family scores with effect sizes varying between 0.9 and 2.4 across traits. Only FSIQ and vocabulary scores showed a significant positive correlation between probands and non-carrier relatives across families (R2~0.4). Variability in family FSIQ also cross-predicted variability in proband ASD trait severity. Cluster analysis across all trait-relative pairings revealed that variability in parental psychopathology was more weakly coupled to their XYY versus their euploid offspring. Researchers presented a suite of generalizable methods for modeling variable penetrance in aneuploidy and copy number variations (CNV) carriers using family data. The methods updated estimates of phenotypic penetrance for XYY and suggested that the predictive utility of family data was likely to vary for different traits and gene dosage disorders. 

 

Link:jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-021-09360-7