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The moderating role of smoking exposure in the relationship between the nicotinic acetylcholine receptor gene cluster and nicotine dependence

Award Number: R21CA226300
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Progress in our ability to evaluate the interaction between genetic effects and environmental factors in understanding risk for nicotine dependence has been significantly impeded by inadequate single study sample sizes and meta analyses that are necessarily limited to the estimation of effect sizes for research questions that have been previously addressed within single studies. Fortunately, recent methodological innovations now permit the combination of data sets that differ in terms of study design, populations, and measures. This integrative data analysis (IDA) allows us to pool the raw data from multiple studies, allowing us to test new hypotheses and results in more powerful, more comprehensive, and more rigorous studies than we achieve through analysis of single studies or by using traditional meta analytic techniques. The present research will combine both an innovative approach (IDA) and innovative statistical methods (moderated nonlinear factor analysis; MNLFA and time-varying effects models; TVEM), to evaluate the association between genetic variants in the CHRNA5/CHRNA3/CHRNB4 and CHRNA6/CHRNB3 regions and nicotine dependence symptoms across levels of smoking exposure. Taking advantage of existing resources, we will pool extant data from the Social Emotional Contexts of Adolescent Smoking Project (SECASP), The National Longitudinal Study of Adolescent Health (AddHealth), the National Youth Survey Family Study (NYSFS) and the Study of Addiction: Genetics and Environment (SAGE) to evaluate changes in the association between SNPs in the acetylcholine receptor gene clusters and an empirically harmonized nicotine dependence score across levels of smoking exposure and to estimate the additional contribution of timing of smoking exposure in explaining the association between individual genetic variants and nicotine dependence symptoms. The innovative methods of data integration with MNLFA will allow us to begin to explore exposure varying effects in an extremely cost-effective manner in that we will leverage previous investment in tracking, contacting, assessing, and collecting DNA from 4 large studies assessing adolescents and adults. The empirically based nicotine dependence symptom score derived from the cross-study MNLFA model will provide a much more sensitive measure of the nicotine dependence phenotype than traditional methods of scoring within study, and one that is uniquely harmonized to account for between study differences.


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 = -$200 )
2024	2021	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cancer Cause and Prevention Research	000	2	11/21/2023	NON-COMPETING CONTINUATION	-$200
														Subtotal = -$200

Issue Date FY: 2021 ( Subtotal = $188,374 )
2021	2021	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cancer Cause and Prevention Research	000	2	4/1/2021	NON-COMPETING CONTINUATION	$188,374
														Subtotal = $188,374

Issue Date FY: 2020 ( Subtotal = $238,888 )
2020	2020	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cancer Cause and Prevention Research	000	1	2/14/2020	NEW	$238,888
														Subtotal = $238,888

Grand Total All Awards = $427,062

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The moderating role of smoking exposure in the relationship between the nicotinic acetylcholine receptor gene cluster and nicotine dependence

Award Number: R21CA226300

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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