A. Corvin

MiR-137-derived polygenic risk: effects on cognitive performance in patients with schizophrenia and controls

Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of MIR137 expression. This list was cross-referenced with genome-wide schizophrenia association data to construct individual polygenic scores. We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (n=108) and face processing tasks (n=83). Increased polygenic risk within the empirically derived miR-137 regulated gene score was associated with significantly lower performance on intelligence quotient, working memory and episodic memory. These effects were observed most clearly at a polygenic threshold of P=0.05, although significant results were observed at all three thresholds analyzed. This association was found independently for the gene set as a whole, excluding the schizophrenia-associated MIR137 SNP itself. Analysis of the spatial working memory fMRI task further suggested that increased risk score (thresholded at P=10−5) was significantly associated with increased activation of the right inferior occipital gyrus. In conclusion, these data are consistent with emerging evidence that MIR137 associated risk for schizophrenia may relate to its broader downstream genetic effects.

Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018)

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from inflation in the FDR [false discovery rate], as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence.

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium (vol 22, pg 336, 2017)

This corrects the article DOI: dx.doi.org/10.1038

Erratum: Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen: Evidence for linkage on chromosomes 6q16-q21, 4q12-q21, 9p21, 10p14-p12 and 18q22 (Molecular Psychiatry (2005) 10, (831-841) DOI: 10.1038/sj.mp.4001684)

Correction to: Molecular Psychiatry (2005) 10, 831–841. doi:10.1038/sj.mp.4001684 Following publication of the above article, the authors noticed that Figure 1 did not include a color key detailing the line colors. The key is indicated in the revised figure on pages 1141–1143.

Stage 2 of the Wellcome Trust UK–Irish bipolar affective disorder sibling-pair genome screen: evidence for linkage on chromosomes 6q16–q21, 4q12–q21, 9p21, 10p14–p12 and 18q22 - Corrigendum

Correction to: Molecular Psychiatry (2005) 10, 831–841. doi:10.1038/sj.mp.4001684 Following publication of the above article, the authors noticed that Figure 1 did not include a color key detailing the line colors. The key is indicated in the revised figure on pages 1141–1143.