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Genetic risk factors for alcoholic cirrhosis - genome-wide case-control study

Award Number: R01AA018389
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/25/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2022

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Genetic risk factors for alcoholic cirrhosis - genome-wide case-control study - Alcoholic liver cirrhosis (ALC) causes a significant mortality worldwide. World Health Organization 2014 Report on ‘alcohol and health’ reports 50% of liver cirrhosis mortality worldwide is due to alcohol, reaching as high as ~60% in north America and Europe. In principle, all alcoholic liver diseases are preventable with appropriate behavioral and lifestyle change, including pharmaceutical approaches. However, progress in developing specific pharmaceutical interventions has been hampered by poor understanding of both genetic and non-genetic factors contributing towards the pathogenesis of this disease. The OVERALL GOAL is to identify loci, genes and polymorphisms underlying genetic risk for the development of ALC in heavy drinkers. To do this the multinational GenomALC Consortium has successfully collected extensive phenotype data and blood/DNAs from >5000 heavy drinkers with and without cirrhosis which will be subjected to genotyping via genome-wide SNP association approach in 2016-2017 (UO1-AA018389). Through other significant collaborations, the consortium has access to additional ~2000 genotype- phenotype data making it the largest discovery cohort for ALC genetics. The consortium has also done the groundwork in identifying and accessing ‘mega-cohort’ Genomics Biobanks (e.g UK Biobank) as independent validation cohorts. The specific aims of the current application are, aim 1: To identify genetic risk factors for ALC through case-control GWAS in GenomALC discovery cohort (n=~7411); aim 2: To confirm allelic associations in independent validation cohorts available from established ‘mega-cohort’ genomic databases; aim 3: To perform meta-analysis with results from other GWAS on alcoholic cirrhosis; aim 4: To examine overlap in genetic risk between alcoholic cirrhosis and potentially related diseases and biomarkers of cirrhosis. The GenomALC team (geneticists, genetic statisticians, clinicians) has the right expertise, skills and established infrastructure to perform these analyses. This large case-control GWAS has the power to identify novel SNPs, create new knowledge and infer pathways/mechanisms leading to alcoholic cirrhosis, thus identifying potential targets for new or repurposed drug treatments.


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 = $0 )
2024	2019	SOUTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION	5901 E 7TH ST	LONG BEACH	CA	90822	LOS ANGELES	USA	Alcohol Research Programs	000	7	9/17/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = -$72,288 )
2023	2019	SOUTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION	5901 E 7TH ST	LONG BEACH	CA	90822	LOS ANGELES	USA	Alcohol Research Programs	000	7	5/15/2023	NON-COMPETING CONTINUATION	-$72,288
														Subtotal = -$72,288

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	SOUTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION	5901 E 7TH ST 151	LONG BEACH	CA	90822	LOS ANGELES	USA	Alcohol Research Programs	000	7	9/20/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $336,491 )
2019	2019	SOUTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION	5901 E 7TH ST 151	LONG BEACH	CA	90822	LOS ANGELES	USA	Alcohol Research Programs	001	7	9/25/2019	NON-COMPETING CONTINUATION	$0
2019	2019	SOUTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION	5901 E 7TH ST 151	LONG BEACH	CA	90822	LOS ANGELES	USA	Alcohol Research Programs	000	7	8/28/2019	NON-COMPETING CONTINUATION	$336,491
														Subtotal = $336,491

Grand Total All Awards = $264,203

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Genetic risk factors for alcoholic cirrhosis - genome-wide case-control study

Award Number: R01AA018389

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/25/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2022

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