Age-Dependent Pleiotropy Between General Cognitive Function and Major XXXX .

@entity146 @entity73 @entity72 @entity161 @entity195
BACKGROUND: General @entity73 predicts @entity146 across the life course. This study examines the role of pleiotropy in explaining the link between @entity73 and @entity146 . METHODS: We used two large genome-wide association study data sets on @entity73 -one from older age, n = 53,949, and one from childhood, n = 12,441. We also used genome-wide association study data on educational attainment, n = 95,427, to examine the validity of its use as a proxy phenotype for @entity73 . Using a new method, linkage disequilibrium regression, we derived genetic correlations, free from the confounding of clinical state between @entity146 and @entity73 . RESULTS: We found a genetic correlation of .711, (p = 2.26e-12) across the life course for general @entity73 . We also showed a positive genetic correlation between @entity72 and @entity73 in childhood (rg = .360, p = .0009) and for educational attainment (rg = .322, p = 1.37e-5) but not in older age. In @entity161 , we found a negative genetic correlation between older age @entity73 (rg = -.231, p = 3.81e-12) but not in childhood or for educational attainment. For @entity195 , we found negative genetic correlations with childhood @entity73 (rg = -.341, p = .001), educational attainment (rg = -.324, p = 1.15e-5), and with older age @entity73 (rg = -.324, p = 1.78e-5). CONCLUSIONS: The pleiotropy exhibited between @entity73 and @entity146 changed across the life course. These age-dependent associations might explain why negative selection has not removed variants causally associated with @entity72 or @entity161 .
