Emma E.M. Knowles, Melanie A. Carless, Marcio A.A. de Almeida, Joanne E. Curran, D. Reese McKay, Emma Sprooten, Thomas D. Dyer, Harald H. Go¨ring, Rene Olvera, Peter Fox, Laura Almasy, Ravi Duggirala, Jack W. Kent Jr., John Blangero, and David. C. Glahn

American Journal of Medical Genetics: Neuropsychiatric Genetics (2013)

It is well established that risk for developing psychosis is largely
mediated by the influence of genes, but identifying precisely
which genes underlie that risk has beenproblematic. Focusing on
endophenotypes, rather than illness risk, is one solution to this
problem. Impaired cognition is a well-established endophenotype
of psychosis. Here we aimed to characterize the genetic
architecture of cognition using phenotypically detailed models
as opposed to relying on general IQ or individual neuropsychological
measures. In so doing we hoped to identify genes that
mediate cognitive ability, which might also contribute to psychosis
risk. Hierarchical factor models of genetically clustered
cognitive traits were subjected to linkage analysis followed by
QTL region-specific association analyses in a sample of 1,269
Mexican American individuals from extended pedigrees. We
identified four genome wide significant QTLs, two for working
and two for spatial memory, and a number of plausible and
interesting candidate genes. The creation of detailed models of
cognition seemingly enhanced the power to detect genetic effects
on cognition and provided a number of possible candidate genes
for psychosis.

Click here for full text.