Over 100 genetic loci harbor schizophrenia-associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of people with schizophrenia (n = 258) and control subjects (n = 279), creating a resource of gene expression and its genetic regulation. Using this resource, ∼20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3 or SNAP91. Altering expression of FURIN, TSNARE1 or CNTN4 changed neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yielded abnormal migration. Of 693 genes showing significant case-versus-control differential expression, their fold changes were ≤ 1.33, and an independent cohort yielded similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show that schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases. From the study above, identify the following; a. Sampling technique? b. Variables of interest?
Over 100 genetic loci harbor schizophrenia-associated variants, yet how these variants confer
liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal
cortex of people with schizophrenia (n = 258) and control subjects (n = 279), creating a resource
of gene expression and its genetic regulation. Using this resource, ∼20% of schizophrenia loci
have variants that could contribute to altered gene expression and liability. In five loci, only a
single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3 or SNAP91. Altering expression
of FURIN, TSNARE1 or CNTN4 changed neurodevelopment in zebrafish; knockdown of FURIN
in human neural progenitor cells yielded abnormal migration. Of 693 genes showing significant
case-versus-control differential expression, their fold changes were ≤ 1.33, and an independent
cohort yielded similar results. Gene co-expression implicates a network relevant for
schizophrenia. Our findings show that schizophrenia is polygenic and highlight the utility of this
resource for mechanistic interpretations of genetic liability for brain diseases.
From the study above, identify the following;
a. Sampling technique?
b. Variables of interest?
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