We propose using established longitudinal studies of 7300 parents and twin children to investigate how gene environment interplay influences the development of substance abuse (SA). Our focus is on children assessed repeatedly, beginning in pre-adolescence at age 11 and then again at approximately ages 14, 17, 20, 24, and 29, making it possible to examine the development of individual differences within narrowly defined age ranges that correspond roughly to key life transitions associated with important changes in environmental context (starting high school, leaving the parental home, exposure to new peers, etc). Our studies involve representative, community based samples with high participation rates, and thorough age appropriate, psychometrically sound assessments covering 1) substance use, misuse, and dependence; 2) disorders, personality traits, and behaviors related to behavioral disinhibition; 3) psychophysiogical endophenotypes for SA risk; and 4) environmental adversity derived from multiple domains (family relationships, trauma, peer group quality, exposure to substances, etc.) over multiple developmental stages. We propose obtaining blood-based DMA from approximately 5000 study participants which, along with deidentified personal data, will be added to the NIDA Genetics Consortium (NGC) public repository. We will obtain consent to participate in this GEDI initiative from an additional 2300 individuals whose data will already be part of the NGC. We will carry out a 2-stage genome wide association study using a 1M SNP bead array with 1000 parents followed by confirmation genotyping with an additional 2700 parents using three SA related latent phenotypes focused on a) SA risk, b) behavioral disinhibition attributes, and c) brain electrophysiology (event related potentials and oscillations). These three quantitative phenotypes will be developed and refined early in the funding period so as to capture complementary aspects of genetic risk for SA similarly in parents and young adult offspring. Offspring (N=3582) will then be genotyped using candidate genes identified in the parent study as well as in the evolving SA literature. A composite measure of environmental adversity will also be developed and used in hypothesis driven tests of GxE effects in offspring that include examination of the developmental specificity of effects and their replicability across related measures, developmental time points, and offspring samples. Also included will be hypothesis-generating exploratory analyses that take advantage of the richness of the phenotypic data available from our families and the rapid pace of development in molecular biology and statistical genetics. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DA024417-02S1
Application #
7694563
Study Section
Special Emphasis Panel (ZDA1-RXL-E (25))
Program Officer
Sirocco, Karen
Project Start
2007-09-30
Project End
2012-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
2
Fiscal Year
2008
Total Cost
$500,000
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Olde Loohuis, Loes M; Mangul, Serghei; Ori, Anil P S et al. (2018) Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia. Transl Psychiatry 8:96
Samek, Diana R; Hicks, Brian M; Durbin, Emily et al. (2018) Codevelopment Between Key Personality Traits and Alcohol Use Disorder From Adolescence Through Young Adulthood. J Pers 86:261-282
Mangul, Serghei; Yang, Harry Taegyun; Strauli, Nicolas et al. (2018) ROP: dumpster diving in RNA-sequencing to find the source of 1 trillion reads across diverse adult human tissues. Genome Biol 19:36
Rahmani, Elior; Schweiger, Regev; Shenhav, Liat et al. (2018) BayesCCE: a Bayesian framework for estimating cell-type composition from DNA methylation without the need for methylation reference. Genome Biol 19:141
Kang, Eun Yong; Lee, Cue Hyunkyu; Furlotte, Nicholas A et al. (2018) An Association Mapping Framework To Account for Potential Sex Difference in Genetic Architectures. Genetics 209:685-698
Smit, Dirk J A; Wright, Margaret J; Meyers, Jacquelyn L et al. (2018) Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity. Hum Brain Mapp 39:4183-4195
Hormozdiari, Farhad; Zhu, Anthony; Kichaev, Gleb et al. (2017) Widespread Allelic Heterogeneity in Complex Traits. Am J Hum Genet 100:789-802
Bilow, Michael; Crespo, Fernando; Pan, Zhicheng et al. (2017) Simultaneous Modeling of Disease Status and Clinical Phenotypes To Increase Power in Genome-Wide Association Studies. Genetics 205:1041-1047
Liu, M; Malone, S M; Vaidyanathan, U et al. (2017) Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychol Med 47:1116-1125
Samek, Diana R; Hicks, Brian M; Keyes, Margaret A et al. (2017) Antisocial peer affiliation and externalizing disorders: Evidence for Gene × Environment × Development interaction. Dev Psychopathol 29:155-172

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