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Postmortem human brain genomics in neuropsychiatric disorders--how far can we go?

ABSTRACT: Large-scale collection of postmortem human brain tissue and subsequent genomic data generation has become a useful approach for better identifying etiological factors contributing to neuropsychiatric disorders. In particular, studying genetic risk variants in non-psychiatric controls can identify biological mechanisms of risk free from confounding factors related to epiphenomena of illness. While the field has begun moving towards cell type-specific analyses, homogenate brain tissue with accompanying cellular profiles, can still identify useful hypotheses for more focused experiments, particularly when the dysregulated cell types are unknown. Technological advances, larger sample sizes, and focused research questions can continue to further leverage postmortem human brain research to better identify and understand the molecular etiology of neuropsychiatric disorders.

SUBMITTER: Jaffe AE

PROVIDER: S-EPMC4857188 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Postmortem human brain genomics in neuropsychiatric disorders--how far can we go?

Jaffe Andrew E AE

Current opinion in neurobiology 20151210

Large-scale collection of postmortem human brain tissue and subsequent genomic data generation has become a useful approach for better identifying etiological factors contributing to neuropsychiatric disorders. In particular, studying genetic risk variants in non-psychiatric controls can identify biological mechanisms of risk free from confounding factors related to epiphenomena of illness. While the field has begun moving towards cell type-specific analyses, homogenate brain tissue with accompa ...[more]

PMID: 26685806

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Project description: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%) (p<0.001), African-American brain donation rates were as high as 60.5% in referrals from Maryland. Neither African-American nor Caucasian donors differed significantly from non-donors on any demographic or clinical factors ascertained, including age, sex, diagnosis of the donor, or in the relationship of the next-of-kin being contacted (p>0.05). 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<0.05). When African-American participants are identified and approached, African-American families as well as Caucasian families are indeed willing to donate brain tissue on the spot for neuropsychiatric research, which supports the belief that African-American attitudes towards biomedical research may be more favorable than previously thought.

Dataset Information

Postmortem human brain genomics in neuropsychiatric disorders--how far can we go?

Publications

Postmortem human brain genomics in neuropsychiatric disorders--how far can we go?

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