Roadmap for Establishing Large-Scale Genomic Medicine Initiatives in Low- and Middle-Income Countries.

In the post-genomic era, genomic medicine interventions as a key component of personalized medicine and tailored-made health care are greatly anticipated following recent scientific and technological advances. Indeed, large-scale sequencing efforts that explore human genomic variation have been initiated in several, mostly developed, countries across the globe, such as the United States, the United Kingdom, and a few others. Here, we highlight the successful implementation of large-scale national genomic initiatives, namely the Genome of Greece (GoGreece) and the DNA do Brasil (DNABr), aiming to emphasize the importance of implementing such initiatives in developing countries. Based on this experience, we also provide a roadmap for replicating these projects in other low-resource settings, thereby bringing genomic medicine in these countries closer to clinical fruition.

The CSMD1 genome-wide associated schizophrenia risk variant rs10503253 affects general cognitive ability and executive function in healthy males.

BACKGROUND: The single-nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2, has reached genome-wide support as a risk factor for schizophrenia. There is initial but inconclusive evidence for a role of this variant in aspects of cognition. METHODS: We investigated the neurocognitive effects of the CSMD1 rs10503253 (C/A) polymorphism in a large, demographically homogeneous sample of young, healthy Greek Caucasian males (n=1149) phenotyped for a wide range of neuropsychological measures, most of which have been shown to be reliable endophenotypes for schizophrenia. RESULTS: The risk 'A' allele was associated with poorer performance on measures of general cognitive ability, strategy formation, spatial and visual working memory, set shifting, target detection and planning for problem solving but not for emotional decision making. Most of these effects were dependent on risk "A" allele dose, with AA and CC homozygotes being the worse and the best respectively, while CA individuals were intermediate. Potential genotype effects in Stroop and verbal memory performance were also suggested by our dataset. DISCUSSION: These results underline the relevance of the risk "A" allele to neurocognitive functioning and suggest that its detrimental effects on cognition, may be part of the mechanism by which the CSMD1 mediates risk for schizophrenia.

Cognitive and personality analysis of startle reactivity in a large cohort of healthy males.

Subjects with low/undetectable startle are usually excluded from startle studies but few reports not confounded by this factor, show reduced startle in healthy impulsive subjects, or clinical populations with disorders of affect and impulsivity but also in schizophrenia and its prodrome. We examined the relationship of startle reactivity including startle "non-responding" status to cognitive and affective personality traits in a large and ethnically/demographically homogeneous cohort of healthy males from the LOGOS study, Heraklion, Crete. Startle reactivity was monotonically related to sensitivity to reward (higher in "non-responders", lower in strong responders). In addition, "non-responders" had poorer strategy, working memory and sustained attention performance compared to responder tertile groups. More research in clinical and high risk populations is required to examine if low/undetectable startle reactivity is a valuable intermediate phenotype for disorders of affect and impulsivity. It is possible that the "non-responsive" status may capture disease related features such as executive dysfunction.