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Investigating the role of immune genes and inflammatory biomarkers in schizophrenia heterogeneity

Award Number: F30MH132165
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Investigating the role of immune genes and inflammatory biomarkers in schizophrenia heterogeneity - PROJECT SUMMARY/ABSTRACT Schizophrenia is a debilitating neuropsychiatric condition with a strong genetic component but poorly understood biological mechanisms. The strongest signal from genome-wide association studies (GWAS) of schizophrenia lies in the major histocompatibility complex locus and is in part driven by copy number variation in the complement component 4 (C4) gene, an important mediator in the complement cascade. Furthermore, cross-disorder studies implicate shared genetic risk in schizophrenia and autoimmune disorders, suggesting a potential immunogenetic role in pathogenesis. Schizophrenia has been linked to increased levels of peripheral inflammation, and immune biomarkers predict worse outcomes in patients with the disorder. However, it is unclear whether inflammation is a causal factor or a consequence of the disease process, and to what extent immune-regulating genes play a role. This work will investigate the joint role of immune biomarkers and genetics in schizophrenia in a large biobank linked to electronic health records (EHRs). First, a repository of EHRs with longitudinal clinical laboratory data will be used to examine the temporal relationship between immune biomarker levels and schizophrenia diagnoses. Within schizophrenia spectrum patients, these biomarker levels will be assessed for their ability to predict specific clinical outcomes. Second, longitudinal cohorts paralleling those proposed in Aim 1 will be constructed but incorporating whole-genome genotyping data from a subset of ~90,000 individuals that are a part of the BioVU, VUMC’s biorepository resource. Genetic predictors of immune biomarkers will be included in these models and evaluated for their relative contributions to schizophrenia risk and their ability to predict clinical outcomes. Mediation analyses will then be conducted to investigate causal pathways linking C4 CNV and immune biomarker alterations in schizophrenia in BioVU. These analyses will be replicated and meta- analyzed in additional well-powered EHR-linked biobanks from the Million Veteran Program and All of Us research program. The proposed studies will elucidate the poorly understood relationships between immune-regulating genetic risk factors, immune biomarkers, and clinical heterogeneity in schizophrenia spectrum disorders. Understanding these relationships will yield mechanistic insights and uncover potentially clinically useful biomarkers of schizophrenia disease course.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $55,114 )
2026	2026	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	001	4	5/6/2026	NON-COMPETING CONTINUATION	$576
2026	2026	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	4	12/29/2025	NON-COMPETING CONTINUATION	$54,538
														Subtotal = $55,114

Issue Date FY: 2025 ( Subtotal = $53,915 )
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	3	12/5/2024	NON-COMPETING CONTINUATION	$53,351
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	001	3	9/8/2025	NON-COMPETING CONTINUATION	$564
														Subtotal = $53,915

Issue Date FY: 2024 ( Subtotal = $34,126 )
2024	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	001	2	8/7/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	2	12/13/2023	NON-COMPETING CONTINUATION	$32,846
														Subtotal = $34,126

Issue Date FY: 2023 ( Subtotal = $31,904 )
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	1	12/22/2022	NEW	$31,904
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	001	1	12/22/2022	NEW	$0
														Subtotal = $31,904

Grand Total All Awards = $175,059

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Investigating the role of immune genes and inflammatory biomarkers in schizophrenia heterogeneity

Award Number: F30MH132165

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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