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1/2 Identification and Validation of Expression Quantitative Trait Loci (eQTLs) in discrete cell types across human brain development

Award Number: R01MH122678
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Functional genomic analyses of the developing human brain have revealed highly dynamic spatiotemporal patterns of gene expression and epigenetic changes during prenatal and early postnatal development and across brain regions. Disruptions of these developmentally dynamic processes have been implicated by numerous complementary analyses in the etiology of multiple neurodevelopmental and neuropsychiatric disorders. Expression quantitative trait loci (eQTLs), along with splicing quantitative trait loci (sQTLs) and structural variant quantitative trait loci (svQTLs), are genomic variants that differ between individuals, with these differences correlating with functional changes to gene expression or splicing behavior. Many of these QTLs show specificity to tissues, brain regions, developmental stages, or cell types, and a proportion overlap with known genetic risk factors of human disorders. Here, we propose to pursue three integrated Aims, including whole-genome sequencing and both bulk tissue and single-nuclei RNA sequencing, to identify genomic variants, eQTL/sQTL/svQTLs, and patterns of gene expression and co-expression in two regions of the human brain across mid-fetal development through to adolescence. In addition, we will apply novel and newly developed computational tools to associate these QTLs with specific cell types and loci or genes implicated in neuropsychiatric disorders. By so doing we will augment, and dramatically expand upon, earlier efforts to understand QTLs and their roles in neural development, function, and neuropsychiatric disorders.


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: 2025 ( Subtotal = $582,487 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Mental Health Research Grants	000	5	12/20/2024	NON-COMPETING CONTINUATION	$582,487
														Subtotal = $582,487

Issue Date FY: 2024 ( Subtotal = $759,989 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Mental Health Research Grants	001	4	8/16/2024	NON-COMPETING CONTINUATION	$75,998
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Mental Health Research Grants	000	4	1/16/2024	NON-COMPETING CONTINUATION	$683,991
														Subtotal = $759,989

Issue Date FY: 2023 ( Subtotal = $758,346 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Mental Health Research Grants	000	3	4/5/2023	NON-COMPETING CONTINUATION	$758,346
														Subtotal = $758,346

Grand Total All Awards = $2,100,822

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1/2 Identification and Validation of Expression Quantitative Trait Loci (eQTLs) in discrete cell types across human brain development

Award Number: R01MH122678

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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