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Integrating case-control transcriptomic and genetic data in admixed individuals to identify disease genes for schizophrenia and bipolar disorder

Award Number: R01MH115676
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Genome-wide association studies (GWAS) have identified hundreds of genomic loci that increase disease susceptibility for schizophrenia (SCZ) and bipolar disorder (BP). We and others have shown that integration of functional molecular data, including transcript abundance levels, can be used to decipher causal insights from GWAS-identified allelic variant to gene to disease susceptibility. The identification of genetic risk factors and causal interpretations provide the greatest potential for the future of personalized genomic medicine. These studies and advances, however, have mostly been performed in individuals of European ancestry, thereby exacerbating health disparities of most vulnerable populations of diverse and admixed genetic ancestries. At this time, NIMH is leading the effort for genetic discoveries in underrepresented populations through funding of large- scale GWAS projects of SCZ and BP, but it is necessary to simultaneously increase the genetic diversity of functional molecular data for data integration and deciphering causal biological effects involved in SCZ and BP. We will tackle the lack of diversity in integrative transcriptomic studies for the deciphering of genetic susceptibility of SCZ and BP in Latino admixed populations, through deliberate integration of novel statistical method development with new transcriptomic data generation. We will generate transcriptome data in 1,500 Latino individuals (500 SCZ cases, 500 BP cases, 500 controls) as a public resource to generate new insights about the molecular mechanisms that contribute to risk of SCZ and BP. At the same time, we will develop new statistical methods that leverage the admixture process to improve the power of mapping genetic effects on expression in Latino individuals. We will incorporate the local and global genetic ancestries within admixed individuals to increase power of transcriptome-wide association (TWAS) and expression quantitative trait score (eQTS) studies to identify novel susceptibility genes. We will integrate new transcriptomic data in Latino individuals with ongoing Latino GWAS of SCZ and BP involving tens of thousands of Latino individuals both to generate new biological hypotheses and to validate our new statistical methods. The most promising causal variants and susceptibility genes will undergo functional validation. Our efforts will result in a large public gene expression resource, novel statistical tools, and new biological findings validated in functional assays. Our findings may yield clinically relevant applications for diagnosis and treatment for SCZ and BP particularly in Latino individuals that have been traditionally underserved in large-scale genomic studies.


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: 2024 ( Subtotal = $458,180 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10920 WILSHIRE BLVD STE 500	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	7	2/7/2024	NON-COMPETING CONTINUATION	$458,180
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	002	6	4/4/2024	COMPETING CONTINUATION	$622,629
2024	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	001	5	4/4/2024	NON-COMPETING CONTINUATION	-$622,629
														Subtotal = $458,180

Issue Date FY: 2023 ( Subtotal = $541,539 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	001	6	4/6/2023	COMPETING CONTINUATION	$541,539
2023	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	5	3/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $541,539

Issue Date FY: 2022 ( Subtotal = $748,802 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	5	2/19/2022	NON-COMPETING CONTINUATION	$673,922
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	001	5	5/13/2022	NON-COMPETING CONTINUATION	$74,880
														Subtotal = $748,802

Issue Date FY: 2021 ( Subtotal = $754,730 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	000	4	2/11/2021	NON-COMPETING CONTINUATION	$754,730
														Subtotal = $754,730

Issue Date FY: 2020 ( Subtotal = $746,636 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	000	3	4/7/2020	NON-COMPETING CONTINUATION	$746,636
														Subtotal = $746,636

Issue Date FY: 2019 ( Subtotal = $757,259 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	000	2	1/22/2019	NON-COMPETING CONTINUATION	$757,259
														Subtotal = $757,259

Issue Date FY: 2018 ( Subtotal = $823,755 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	001	1	8/14/2018	NEW	-$1,192
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	000	1	3/12/2018	NEW	$824,947
														Subtotal = $823,755

Grand Total All Awards = $4,830,901

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Integrating case-control transcriptomic and genetic data in admixed individuals to identify disease genes for schizophrenia and bipolar disorder

Award Number: R01MH115676

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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