Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
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Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. / Haney, Jillian R.; CommonMind Consortium; PsychENCODE Consortium; iPSYCH-BROAD Working Group.
In: Science, Vol. 359, No. 6376, 09.02.2018, p. 693-697.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
AU - Gandal, Michael J.
AU - Haney, Jillian R.
AU - Werge, Thomas M.
AU - CommonMind Consortium
AU - PsychENCODE Consortium
AU - iPSYCH-BROAD Working Group
PY - 2018/2/9
Y1 - 2018/2/9
N2 - The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders—autism, schizophrenia, bipolar disorder, depression, and alcoholism—compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism–based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.
AB - The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders—autism, schizophrenia, bipolar disorder, depression, and alcoholism—compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism–based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.
UR - http://www.scopus.com/inward/record.url?scp=85041925301&partnerID=8YFLogxK
U2 - 10.1126/science.aad6469
DO - 10.1126/science.aad6469
M3 - Journal article
C2 - 29439242
AN - SCOPUS:85041925301
VL - 359
SP - 693
EP - 697
JO - Science
JF - Science
SN - 0036-8075
IS - 6376
ER -
ID: 199177196