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BackgroundOf the 108 Schizophrenia (SZ) risk-loci discovered through genome-wide association studies (GWAS), 96 are not altering the sequence of any protein. Evidence linking non-coding risk-SNPs and genes may be established using expression quantitative trait loci (eQTL). However, other approaches such allelic expression quantitative trait loci (aeQTL) also may be of use.MethodsWe applied both the eQTL and aeQTL analysis to a biobank of deeply sequenced RNA from 680 dorso-lateral pre-frontal cortex (DLPFC) samples. For each of 340 genes proximal to the SZ risk-SNPs, we asked how much SNP-genotype affected total expression (eQTL), as well as how much the expression ratio between the two alleles differed from 1:1 as a consequence of the risk-SNP genotype (aeQTL).ResultsWe analyzed overlap with comparable eQTL-findings: 16 of the 30 risk-SNPs known to have gene-level eQTL also had gene-level aeQTL effects. 6 of 21 risk-SNPs with known splice-eQTL had exon-aeQTL effects. 12 novel potential risk genes were identified with the aeQTL approach, while 55 tested SNP-pairs were found as eQTL but not aeQTL. Of the tested 108 loci we could find at least one gene to be associated with 21 of the risk-SNPs using gene-level aeQTL, and with an additional 18 risk-SNPs using exon-level aeQTL.ConclusionOur results suggest that the aeQTL strategy complements the eQTL approach to susceptibility gene identification.

Increased African-American research participation is critical to the applicability and generalizability of biomedical research, as population diversity continues to increase both domestically and abroad. Yet numerous studies document historical origins of mistrust, as well as other barriers that may contribute to resistance in the African-American community towards participation in biomedical research. However, a growing body of more recent scientific evidence suggests that African-Americans value research and are willing to participate when asked. In the present study, we set out to determine factors associated with research participation of African-American families in postmortem human brain tissue donation for neuropsychiatric disorders as compared with Caucasian families, from same-day medical examiner autopsy referrals. We retrospectively reviewed brain donation rates, as well as demographic and clinical factors associated with donation in 1,421 consecutive referrals to three medical examiner's offices from 2010-2015. Overall, 69.7% of all next-of-kin contacted agreed to brain donation. While Caucasian families consented to donate brain tissue at a significantly higher rate (74.1%) than African-American families (57.0%) (p0.05). However, Caucasian donors were significantly older, had more years of education, were more likely to be referred for study due to a psychiatric diagnosis, more likely to have comorbid substance abuse, and more likely to have died via suicide, as compared with African-American donors (p

Fibroblasts can be collected from deceased individuals, grown in culture, reprogrammed into induced pluripotent stem cells (iPSCs), and then differentiated into a multitude of cell types, including neurons. Past studies have generated iPSCs from somatic cell biopsies from either animal or human subjects. Previously, fibroblasts have only been successfully cultured from postmortem human skin in two studies. Here we present data on fibroblast cell cultures generated from 146 scalp and/or 53 dura mater samples from 146 postmortem human brain donors. In our overall sample, the odds of successful dural culture was almost two-fold compared with scalp (OR = 1.95, 95% CI: [1.01, 3.9], p = 0.047). Using a paired design within subjects for whom both tissues were available for culture (n = 53), the odds of success for culture in dura was 16-fold as compared to scalp (OR = 16.0, 95% CI: [2.1-120.6], p = 0.0007). Unattended death, tissue donation source, longer postmortem interval (PMI), and higher body mass index (BMI) were associated with unsuccessful culture in scalp (all p