the Frontal Cortex and Hippocampus across Development and Schizophrenia Leonardo Collado-Torres Staff Scientist II @fellgernon Data Science I with Andrew Jaffe
$80 billion/year. Neuropsychiatric conditions are the leading cause of disability in young people worldwide. 70% 70% of youth in the juvenile justice system are living with at least one mental health condition. Traumatic brain injury is the leading cause of long-term disability in children and adults younger than 35 years. 1 in 4 experience mental illness in a given year. More veterans die of suicide than in combat at rate of 20 suicides per day. 2
TRUE FDR.5perc None DLPFC HIPPO Both TWAS Z by brain region Removed sex, SNP PCs 1-5, expression PCs Kept diagnosis jaffelab::cleaningY() TWAS Z scores are correlated among DLPFC & HIPPO GWAS: CLOZUK
0 5 −5 0 5 −6 −3 0 3 6 −6 −3 0 3 6 TWAS Z score SCZD vs control t−statistic BEST GWAS p < 5e−08 FALSE TRUE TWAS vs SCZD differential expression Risk Loci by BEST GWAS TWAS and SCZD statistics are not related
103 116 95 124 With TWAS weights 86 (83.5%) 93 (80.2%) 78 (82.1%) 101 (81.5%) TWAS FDR <5% 79 (91.9%) 88 (93.5%) 73 (93.6%) 94 (93.1%) TWAS Bonferroni <5% 61 (70.9%) 68 (73.1%) 54 (69.2%) 75 (74.3%) TWAS results are complementary to eQTLs in risk loci ~80% of risk loci with eQTLs have TWAS weights, ~90% and ~70% of these are FDR or Bonferroni significant
development • Novel region-specific schizophrenia genetic risk features • Decreased regional functional coherence in schizophrenia • Public brain gene expression and eQTL resource at http://eqtl.brainseq.org/phase2 BrainSeq Phase II summary
E. Burke • Amy Peterson • Joo Heon Shin • Richard E. Straub • Anandita Rajpurohit • Stephen A. Semick • William S. Ulrich • Amanda J. Price • Cristian Valencia • Ran Tao • Amy Deep-Soboslay • Thomas M. Hyde • Joel E. Kleinman • Daniel R. Weinberger+ • Andrew E. Jaffe+ o andrew.jaffe@libd.org o @andrewejaffe 17 • BrainSeq Consortium • LIBD @lieberinstitute Funding github.com/LieberInstitute/brainseq_phase2 doi.org/10.1016/j.neuron.2019.05.013