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Alliey-Rodriguez, N.

Publications and source records attributed to Alliey-Rodriguez, N..

3 recordsLinked to original sources
bioRxiv2017

Genetic Analysis of Deep Phenotyping Projects in Common Disorders

Several studies of complex psychotic disorders with large numbers of neurobiological phenotypes are currently under way, in living patients and controls, and on assemblies of brain specimens. Genetic analyses of such data typically present challenges, because of the choice of underlying hypotheses on genetic architecture of the studied disorders and phenotypes, large numbers of phenotypes, the appropriate multiple testing corrections, limited numbers of subjects, imputations required on missing phenotypes and genotypes, and the cross-disciplinary nature of the phenotype measures. Advances in genotype and phenotype imputation, and in genome-wide association (GWAS) methods, are useful in dealing with these challenges. As compared with the more traditional single-trait analyses, deep phenotyping with simultaneous genome-wide analyses serves as a discovery tool for previously unsuspected relationships of phenotypic traits with each other, and with specific molecular involvements.

genetics↗
bioRxiv2017

Common variants of NRXN1, LRP1B and RORA are associated with increased ventricular volumes in psychosis - GWAS findings from the B-SNIP deep phenotyping study

Schizophrenia, Schizoaffective, and Bipolar Disorders share common illness traits, intermediate phenotypes and a partially overlapping polygenic basis. We performed GWAS on deep phenotyping data, including structural MRI and DTI, clinical, and behavioral scales from 1,115 cases and controls. Significant associations were observed with two cerebrospinal fluid volumes: the temporal horn of left lateral ventricle was associated with NRXN1, and the volume of the cavum septum pellucidum was associated with LRP1B and RORA. Both volumes were associated with illness. Suggestive associations were observed with local gyrification indices, fractional anisotropy and age at onset. The deep phenotyping approach allowed unexpected genetic sharing to be found between phenotypes, including temporal horn of left lateral ventricle and age at onset.

genetics↗
bioRxiv2017

Higher genetic risk of schizophrenia is associated with lower cognitive performance in healthy individuals

Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of the genetic risk of schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BACS) that is greatly reduced in psychosis patients; a measure of premorbid intelligence that is minimally affected by psychosis (the Wide-Range Achievement Test, WRAT); and educational attainment (EY), which covaries with both BACS and WRAT. Using genome-wide SNP data from 314 psychotic and 423 healthy research participants in the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Consortium, we investigated the association of PRSSCZ with BACS, WRAT and EY. Among apparently healthy individuals, greater genetic risk for schizophrenia (PRSSCZ) was associated with lower BACS scores (r = -0.19, p = 1 x 10-4 at PT = 1 x 10-4) but did not associate with WRAT or EY, suggesting that these areas of cognition vary in their etiologic relationships with schizophrenia. Among individuals with psychosis, PRSSCZ did not associate with variation in cognitive performance. These findings suggest that the same cognitive abilities that are disrupted in psychotic disorders are also associated with schizophrenia genetic risk in the general population. Specific cognitive phenotypes, independent of education or general intelligence, could be more deeply studied for insight into the specific processes affected by the genetic influences on psychosis.\n\nSignificancePsychotic disorders such as schizophrenia often involve profound cognitive deficits, the genetic underpinnings of which remain to be elucidated. Poor educational performance early in life is a well-known risk factor for future psychotic illness, potentially reflecting either shared genetic influences or other risk factors that are epidemiologically correlated. Here we show that, in apparently healthy individuals, common genetic risk factors for schizophrenia associate with lower performance in areas of cognition that are impaired in psychotic disorders but do not associate independently with educational attainment or more general measures of intelligence. These results suggest that specific cognitive phenotypes - independent of education or general intelligence - could be more deeply studied for insight into the processes affected by the genetic influences on psychosis.

genetics↗