Browsing by Author "Chopra, Pankaj"

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    Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion
    (2020) Cleynen, Isabelle; Engchuan, Worrawat; Hestand, Matthew; Heung, Tracy; Holleman, Aarón M.; Johnston, Richard; Monfeuga, Thomas; McDonald McGinn, Donna M.; Gur, Raquel E.; Morrow, Bernice E.; Swillen, Ann; Vorstman, Jacob A. S; Bearden, Carrie E.; Chow, Eva W. C.; van den Bree, Marianne; Emanuel, Beverly S.; Vermeesch, Joris R.; Warren, Stephen T.; Owen, Michael J.; Chopra, Pankaj; Cutler, David J.; Duncan, Richard; Kotlar, Alex V.; Mulle, Jennifer G.; Voss, Anna J.; Zwick, Michael E.; Diacou, Alexander; Golden, Aaron; Guo, Tingwei; Lin, Jhih Rong; Wang, Tao; Zhang, Zhengdong; Zhao, Yingjie; Marshall, Marshall; Merico, Daniele; Jin, Andrea; Lilley, Brenna; Salmons, Harold I.; Oanh, Tran; Pardinas, Antonio; Repetto, Gabriela
    Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6 ). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present
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    PEMapper and PECaller provide a simplified approach to whole-genome sequencing
    (National Academy of Sciences, 2017) Johnston, Richard; Chopra, Pankaj; Wingo, Thomas; Patel, Viren; Epstein, Michael; Mulle, Jennifer; Warren, Stephen; Zwick, Michael; Cutler, David; International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome
    The analysis of human whole-genome sequencing data presents significant computational challenges. The sheer size of datasets places an enormous burden on computational, disk array, and network resources. Here, we present an integrated computational package, PEMapper/PECaller, that was designed specifically to minimize the burden on networks and disk arrays, create output files that are minimal in size, and run in a highly computationally efficient way, with the single goal of enabling whole-genome sequencing at scale. In addition to improved computational efficiency, we implement a statistical framework that allows for a base by base error model, allowing this package to perform as well or better than the widely used Genome Analysis Toolkit (GATK) in all key measures of performance on human whole-genome sequences.

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