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Study Description

This study explores the temporal dynamics and genetic control of transcription in the human dorsolateral prefrontal cortex in postmortem tissue from 269 subjects without neuropathological and neuropsychiatric diagnosis from fetal development through aging. We discover fast changes in gene expression occurring during early brain development. Later in life, the changes are considerably slower. Many genes reverse pattern of expression between fetal and early postnatal development. We identify thousands of strong associations of SNPs with gene expression. DNA for genotyping was obtained from the cerebella and applied to either Illumina 650K or 1 million BeadArrays - only genotypes common to both platforms are analyzed here. Genotypes were called using BeadExpress software.

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Study Inclusion/Exclusion Criteria

Postmortem human brains from the NIMH Brain Tissue Collection in the Clinical Brain Disorders Branch (NIMH, CBDB) were obtained at autopsy primarily from the Offices of the Chief Medical Examiner of the District of Columbia, and of the Commonwealth of Virginia, Northern District, all with informed consent from the legal next of kin (protocol #90-M-0142 approved by the NIMH/NIH Institutional Review Board). Additional postmortem fetal, infant, child, and adolescent brain tissue samples were provided by the National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders (BTB: http://medschool.umaryland.edu/BTBank/) under contracts NO1-HD-4-3368 and NO1-HD-4-3383. Toxicological analysis was performed on every case. Subjects with evidence of macro- or microscopic neuropathology, drug use, alcohol abuse, or psychiatric illness were excluded. SNPs were removed if the call rate was <98% (mean call rate for this study >99%), if not in HWE (p<0.001) in Caucasian or African American subjects, or not polymorphic (MAF<0.01). The total number of SNPs remaining in the analysis was 598,767 (92.1%).

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina HumanHap650Yv3.0 660918 51469
Whole Genome Genotyping Illumina Human1M-Duov3_B 1185051 1049348
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