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Estimating the genetic and environmental architecture of psychiatric disorders

Award Number: R01MH100141
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/04/2013
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Estimating the genetic and environmental architecture of psychiatric disorders - PROJECT SUMMARY Understanding the genetic and environmental architecture of traits has been one of the central goals of behavioral genetics over the last fifty years. Traditional approaches using twins and families have shown that most traits, including psychiatric disorders, are highly heritable. More recently, methods that estimate heritability (h2) from single nucleotide polymorphisms (SNPs) in unrelated individuals (h2SNP) have demonstrated the importance of common variants to the genetic variation underlying complex traits. In turn, the realization that common variants are responsible for substantial trait heritability has motivated continued investment in large whole-genome datasets, which have allowed the discovery of thousands of SNPs reliably associated with complex traits. In the midst of this deluge of data, however, fundamental questions about the genetic and environmental architecture of traits remain unanswered, and new methodological approaches that leverage increasingly large whole-genome datasets are needed to answer them. In this Renewal application, we build on our previous methodological work to answer four high-level questions about the genetic and environmental architecture of complex traits. First, estimates of h2SNP for psychiatric disorders remain lower than estimates of h2 from twin and family studies. How much of this “still missing” heritability is due to rare risk variants? Using methods developed during the previous period of our grant, we will provide the best estimates to date of the importance of rare versus common risk variants of schizophrenia, bipolar disorder, and major depression. Second, there appears to be substantial overlap between common risk alleles for psychiatric disorders such as schizophrenia and bipolar disorder. Do rare risk alleles overlap to the same degree, or do they tend to be disorder-specific? We will use extensions of our previously developed methods to help answer this question. Third, the availability of large whole-genome datasets is growing at an unprecedented rate. Can this data be leveraged to answer fundamental questions about the importance of genes and the environment, traditionally the domain of twin and family designs? We propose the development of methodological approaches that use measured genetic data among relatives that exist in large datasets to help answer old questions in new ways that bypass earlier limitations. Finally, it is crucial to understand factors that can bias estimates and lead to incorrect conclusions. We show how assortative mating and gene-by- environment interactions bias existing estimates of h2SNP, and we propose the development of models and software tools that mitigate these biases. By project's end, we anticipate having tools that open up new vistas to behavioral genetics research, allowing for a clearer understanding of the genetic and environmental architecture of psychiatric disorders and other complex traits. Doing so will help guide future analytic and investment decisions.


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 = $0 )
2025	2022	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80303	BOULDER	USA	Mental Health Research Grants	000	10	4/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	10	6/12/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $606,948 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	10	3/28/2022	NON-COMPETING CONTINUATION	$606,948
														Subtotal = $606,948

Issue Date FY: 2021 ( Subtotal = $606,434 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	9	3/20/2021	NON-COMPETING CONTINUATION	$606,434
														Subtotal = $606,434

Issue Date FY: 2020 ( Subtotal = $639,536 )
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	8	5/4/2020	NON-COMPETING CONTINUATION	$639,536
														Subtotal = $639,536

Issue Date FY: 2019 ( Subtotal = $641,706 )
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	002	7	3/26/2019	NON-COMPETING CONTINUATION	$641,706
2019	2018	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	6	11/19/2018	COMPETING CONTINUATION	$810
2019	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	5	11/19/2018	NON-COMPETING CONTINUATION	-$810
														Subtotal = $641,706

Issue Date FY: 2018 ( Subtotal = $698,238 )
2018	2018	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	6	7/5/2018	COMPETING CONTINUATION	$698,238
2018	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST., RM 479 572 UCB	BOULDER	CO	80303	BOULDER	USA	Mental Health Research Grants	000	5	7/3/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $698,238

Issue Date FY: 2017 ( Subtotal = $422,097 )
2017	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST., RM 479 572 UCB	BOULDER	CO	80303	BOULDER	USA	Mental Health Research Grants	001	5	5/25/2017	NON-COMPETING CONTINUATION	$42,210
2017	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST., RM 479 572 UCB	BOULDER	CO	80303	BOULDER	USA	Mental Health Research Grants	000	5	11/18/2016	NON-COMPETING CONTINUATION	$379,887
														Subtotal = $422,097

Issue Date FY: 2016 ( Subtotal = $422,097 )
2016	2016	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	4	11/14/2015	EXTENSION WITH OR WITHOUT FUNDS	$379,887
2016	2016	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	4	3/15/2016	EXTENSION WITH OR WITHOUT FUNDS	$42,210
														Subtotal = $422,097

Issue Date FY: 2015 ( Subtotal = $422,097 )
2015	2015	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	3	11/11/2014	NON-COMPETING CONTINUATION	$379,887
2015	2015	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	3	1/7/2015	NON-COMPETING CONTINUATION	$42,210
														Subtotal = $422,097

Issue Date FY: 2014 ( Subtotal = $377,616 )
2014	2014	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	2	11/19/2013	NON-COMPETING CONTINUATION	$339,855
2014	2014	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	2	2/28/2014	NON-COMPETING CONTINUATION	$37,761
														Subtotal = $377,616

Issue Date FY: 2013 ( Subtotal = $424,880 )
2013	2013	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	1	2/4/2013	NEW	$424,880
														Subtotal = $424,880

Grand Total All Awards = $5,261,649

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Estimating the genetic and environmental architecture of psychiatric disorders

Award Number: R01MH100141

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/04/2013

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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