Kenneth S Kendler1,2, Henrik Ohlsson3, Alexis C Edwards1,2, Jan Sundquist3,4,5, Kristina Sundquist3,4,5. 1. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia. 2. Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia. 3. Center for Primary Health Care Research, Lund University, Malmö, Sweden. 4. Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York. 5. Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Japan.
Abstract
OBJECTIVE: The purpose of this study was to clarify the mediational pathways from genetic risk for alcohol use disorder (AUD) to AUD itself. METHOD: Using information on AUD status from first- through fourth-degree relatives obtained from national registries, we created a genetic risk score for AUD for the Swedish population. We first tested a simple mediational path model in males and females separately, with early onset externalizing psychopathology (EPP), internalizing psychopathology (IPP), and poor educational attainment (EA). We then tested a more complex model in a smaller, older sample of males that contained additional self-report measures from late adolescence. RESULTS: In our basic model, the largest mediational pathway from AUD genetic risk to AUD in both sexes was via high EPP followed by low EA and high IPP. The EPP pathway was considerably stronger in males, the low EA pathway was modestly stronger in females, and the IPP pathway was identical in both sexes. Our more complex model replicated the strong externalizing pathway to AUD, showing that it connected to key downstream risk factors such as early drug and alcohol use and low resilience. CONCLUSIONS: Our models concurred in showing that the strongest mediational pathway for genetic risk to AUD includes externalizing symptoms and disorders, which in turn predict further key downstream risk factors. Pathways through lower EA and IPP had smaller effects. IPP had mixed effects (partly predisposing and partly protective) on downstream risk factors. The largest sex difference was a stronger externalizing pathway to genetic risk to AUD in males than in females.
OBJECTIVE: The purpose of this study was to clarify the mediational pathways from genetic risk for alcohol use disorder (AUD) to AUD itself. METHOD: Using information on AUD status from first- through fourth-degree relatives obtained from national registries, we created a genetic risk score for AUD for the Swedish population. We first tested a simple mediational path model in males and females separately, with early onset externalizing psychopathology (EPP), internalizing psychopathology (IPP), and poor educational attainment (EA). We then tested a more complex model in a smaller, older sample of males that contained additional self-report measures from late adolescence. RESULTS: In our basic model, the largest mediational pathway from AUD genetic risk to AUD in both sexes was via high EPP followed by low EA and high IPP. The EPP pathway was considerably stronger in males, the low EA pathway was modestly stronger in females, and the IPP pathway was identical in both sexes. Our more complex model replicated the strong externalizing pathway to AUD, showing that it connected to key downstream risk factors such as early drug and alcohol use and low resilience. CONCLUSIONS: Our models concurred in showing that the strongest mediational pathway for genetic risk to AUD includes externalizing symptoms and disorders, which in turn predict further key downstream risk factors. Pathways through lower EA and IPP had smaller effects. IPP had mixed effects (partly predisposing and partly protective) on downstream risk factors. The largest sex difference was a stronger externalizing pathway to genetic risk to AUD in males than in females.
Authors: Lorenzo Leggio; George A Kenna; Miriam Fenton; Erica Bonenfant; Robert M Swift Journal: Neuropsychol Rev Date: 2009-01-31 Impact factor: 7.444
Authors: Kenneth S Kendler; Henrik Ohlsson; Alexis C Edwards; Jan Sundquist; Kristina Sundquist Journal: Drug Alcohol Depend Date: 2017-07-29 Impact factor: 4.492
Authors: A C Heath; K K Bucholz; P A Madden; S H Dinwiddie; W S Slutske; L J Bierut; D J Statham; M P Dunne; J B Whitfield; N G Martin Journal: Psychol Med Date: 1997-11 Impact factor: 7.723
Authors: Dongbing Lai; Leah Wetherill; Sarah Bertelsen; Caitlin E Carey; Chella Kamarajan; Manav Kapoor; Jacquelyn L Meyers; Andrey P Anokhin; David A Bennett; Kathleen K Bucholz; Katharine K Chang; Philip L De Jager; Danielle M Dick; Victor Hesselbrock; John Kramer; Samuel Kuperman; John I Nurnberger; Towfique Raj; Marc Schuckit; Denise M Scott; Robert E Taylor; Jay Tischfield; Ahmad R Hariri; Howard J Edenberg; Arpana Agrawal; Ryan Bogdan; Bernice Porjesz; Alison M Goate; Tatiana Foroud Journal: Genes Brain Behav Date: 2019-06-04 Impact factor: 3.449
Authors: Sandra Sanchez-Roige; Abraham A Palmer; Pierre Fontanillas; Sarah L Elson; Mark J Adams; David M Howard; Howard J Edenberg; Gail Davies; Richard C Crist; Ian J Deary; Andrew M McIntosh; Toni-Kim Clarke Journal: Am J Psychiatry Date: 2018-10-19 Impact factor: 18.112