Glowinski, Anne

Jacob, Theodore

Knopik, Valerie S

Lynskey, Michael T

Slutske, Wendy S

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Washington University School of MedicineDigital Commons@BeckerPosters 2007: Alcohol Use Across the Lifespan2007MARC project 4: Australian children of alcoholicfemale twinsWendy S. SlutskeValerie S. KnopikTheodore JacobMichael T. LynskeyAnne GlowinskiFollow this and additional works at: http://digitalcommons.wustl.edu/guzeposter2007Part of the Medicine and Health Sciences CommonsThis Poster is brought to you for free and open access by the 2007: Alcohol Use Across the Lifespan at Digital Commons@Becker. It has been acceptedfor inclusion in Posters by an authorized administrator of Digital Commons@Becker. For more information, please contact engeszer@wustl.edu.Recommended CitationSlutske, Wendy S.; Knopik, Valerie S.; Jacob, Theodore; Lynskey, Michael T.; and Glowinski, Anne, "MARC project 4: Australianchildren of alcoholic female twins" (2007). Posters. Paper 15 Samuel B. Guze Symposium on Alcoholism.http://digitalcommons.wustl.edu/guzeposter2007/15MARC Project 4:Australian Children of Alcoholic Female TwinsWendy S. Slutske, Valerie S. Knopik, Theodore Jacob, Michael T. Lynskey, & Anne GlowinskiBackground• Although it has been widely embraced by the treatment community, and certainly has a great deal of intuitive appeal, it has been difficult to demonstrate empirically a (non-genetic) consequence of being reared by an alcoholic parent.• One critical test for demonstrating an important environmental effect of being reared by an alcoholic parent is to compare the rates of adverse outcomes among the biological offspring of an alcoholic parent to the rates of adverse outcomes among the biological offspring of the unaffected monozygotic cotwin of the alcoholic parent.  • The major aim of this project is to determine whether being raised by an alcoholic parent, in particular an alcoholic mother, increases the risk of adverse outcomes in the offspring after controlling for genetic transmission, and to identify mediators and modifiers of risk-outcome relationships.Limitations of Previous Research• Family studies have demonstrated that offspring of alcoholic parents are at higher risk for adverse outcomes than offspring of nonalcoholic parents, but it is impossible to determine from such studies whether this is due to genetic or environmental transmission of risk. • Twin studies have generally led to the conclusion that family environmental influences do not play a major role in the familial transmission of alcoholism risk.  However, in the twin design the estimate of family environmental effects only includes those that are independent of genetic effects. • Adoption studies have not consistently demonstrated that offspring of alcoholic adoptive parents are at higher risk for adverse outcomes than offspring of nonalcoholic adoptive parents.  Adoption studies are ideal in theory but limited in practice due to the screening of adoptive parents, which results in a restriction in the range of environmental adversity to which adoptive offspring are exposed.• There is a paucity of research focused on the risk of adverse outcomes for offspring of alcoholic mothers. Above are pedigree diagrams of the three types of twin-families included in this study of offspring of twins (shaded circles represent female twins with a history of alcohol use disorder (alcohol dependence (AD) or alcohol abuse (AB) -- AUD): families with at least one monozygotic female twin with a history of AUD, families with at least one dizygotic female twin with a history of AUD, and monozygotic or dizygotic twin families in which both female twins are unaffected with AUDs (control families). Offspring of Twins Research Design1 2 3 4Risk GroupA1 2 3 4Risk GroupB1 2 3 4Risk GroupCAbove are hypothetical results of the risk of adverse outcomes among offspring of twins from different risk categories represented in the previous panel.  Panel ‘A’ represents the risk to offspring when the familial transmission is solely due to genetic effects, panel ‘B’ represents the risk to offspring when the familial transmission is solely due to family environmental effects, and panel ‘C’ represents the risk to offspring when the familial transmission is largely due to genotype x family environmental effects. All panels assume statistical control for paternal psychopathology.Data Collection• Data collection for this project is being done at the Queensland Institute of Medical Research in Brisbane, Australia.• Female twin pairs from the different risk categories have been identified from previous large twin interview surveys.• Female twin pairs are administered structured psychiatric telephone interviews in which they report about themselves, their biological offspring ages 7-22, and the father of the offspring.  Fathers of the offspring are administered structured psychiatric telephone interviews in which they report about themselves. • All offspring ages 11 and older are interviewed. • Follow-up interviews with offspring are conducted every two years for a maximum of four interviews over the entire course of the 10-year study.Key Constructs Assessed• Deviant socialization pathway– impaired parenting, family disruption– deviant peers– academic failure, childhood ADHD, oppositional behavior, and conduct problems• Negative affect pathway– childhood stressors (physical and sexual abuse, traumatic events)– personality trait of neuroticism– internalizing disorders (depression and anxiety)• Pharmacological vulnerability pathway– initial sensitivity to alcohol– drinking motives, alcohol expectancies In addition to collecting information about alcohol use and alcohol  use disorders among all participants, we are assessing constructs related to three hypothesized pathways of the genetic and environmental transmission of alcoholism risk: We are currently in year 8 of this project.  By the end of year 10, we expect the following sample sizes:Risk group Mothers Offspring1 - Mother AUD (AD or AB) 332 5122 - Mother unaffected, MZ cotwin AUD 101 1793 - Mother unaffected, DZ cotwin AUD 104 1714 - Mother unaffected, cotwin unaffected 654 1023Total 1191 1879Recent projects have focused on the relationship between maternal AUD and offspring externalizing behavior problems.Data have been analyzed based on the interviews with 536 mothers of 922 offspring.Risk group Mothers Offspring1 - Mother AUD (AD or AB) 145 2312 - Mother unaffected, MZ cotwin AUD 41 673 - Mother unaffected, DZ cotwin AUD 38 614 - Mother unaffected, cotwin unaffected 312 563Total 536 922Rates of ADHD among offspring from different risk groups Risk group % with ADHDOddsratio1a – Mother alcohol dependent (AD) 10.1 2.53*1b - Mother alcohol abuse (AB) 9.2 1.852 - Mother unaffected, MZ cotwin AUD 11.9 3.16**3 - Mother unaffected, DZ cotwin AUD 1.6 0.324 - Mother unaffected, cotwin unaffected 4.8 1.00These results are consistent with a genetic transmission explanation of the increased risk of ADHD among the offspring of alcoholic mothers (Knopik et al., Psychological Medicine, 2006).Rates of conduct problems among offspring from different risk groupsRisk group % with CPOddsratio1a – Mother alcohol dependent (AD) 13.1 2.43*1b - Mother alcohol abuse (AB) 9.9 1.752 - Mother unaffected, MZ cotwin AUD 14.9 2.82*3 - Mother unaffected, DZ cotwin AUD 1.6 0.274 - Mother unaffected, cotwin unaffected 5.9 1.00These results are consistent with a genetic transmission explanation of the increased risk of conduct problems among the offspring of alcoholic mothers (Knopik et al., in preparation). A major focus of these projects has also been to examine the effect of prenatal exposure to alcohol and tobacco among offspring of alcoholic mothers.  The following two tables illustrate that: 1) Maternal smoking during pregnancy is strongly associated with ADHD and CP among children of alcoholic mothers. 2) Even after controlling for the genetic risk conferred by an alcoholic mother, there remained a strong association between maternal smoking during pregnancy and offspring ADHD and CP.3) The evidence for a genetic transmission explanation for the increased risk of ADHD and CP among the offspring of alcoholic mothers was substantially reduced after controlling for the effect of smoking during pregnancy.ADHDUnadjusted Adjusted% OR 95% CI OR 95% CIMother AD 10.1 2.53* 1.14-5.59Mother AB 9.2 1.85 0.88-3.90 2.47* 1.09-5.59Mother UN, MZ cotwin AD/AB 11.9 3.16* 1.38-7.20Mother UN, DZ cotwin AD/AB 1.6 0.32 0.04-2.59 0.64 0.07-5.50Mother UN, Cotwin UN 4.8 1.00 -- 1.00 --Mother never smoked 3.6 1.00 -- 1.00 --Mother smoked, not during pregnancy 5.1 1.57 0.67-3.67 0.72 0.23-2.22Mother smoked,1st trimester only 9.5 3.02* 1.16-7.89 1.88 0.45-7.81Mother smoked beyond 1st trim., 1-15 cigs 6.8 2.07 0.79-5.42 0.54 0.16-1.83Mother smoked beyond 1st trim., 16+ cigs 24.3 9.47** 4.74-18.95 3.83* 1.09-13.45Mother drank <11 days during pregnancy, never heavily7.1 1.00 --Mother drank 11-35 days, never heavily 6.6 0.91 0.43-1.95Mother drank 36+ days, never heavily 1.3 0.17 0.02-1.17Mother drank heavily, 1-10 days 2.9 0.38 0.05-2.69Mother drank heavily, 11+ days 10.5 1.29 0.29-5.80Maternal AUD, smoking during pregnancy, and offspring ADHDKnopik et al., 2006CPUnadjusted AdjustedOR 95% CI OR 95% CIMother AD 2.43* 1.18-5.00 1.60 0.73-3.53Mother AB 1.75 0.79-3.92 1.46 0.62-3.44Mother UN, MZ cotwin AD/AB 2.82* 1.16-6.83 2.38 0.94-5.83Mother UN, DZ cotwin AD/AB 0.27 0.04-1.99 0.26 0.05-1.93Mother UN, Cotwin UN 1.00 -- 1.00 --Mother never smoked 1.00 -- 1.00 --Mother smoked, not during pregnancy 1.63 0.72-3.68 1.49 0.63-3.40Mother smoked,1st trimester only 2.47 0.97-6.32 1.81 0.65-5.02Mother smoked beyond 1st trim., 1-15 cigs 3.24** 1.61-6.51 2.83** 1.29-6.19Mother smoked beyond 1st trim., 16+ cigs 6.30** 2.63-15.07 5.12** 2.12-12.37Mother drank <11 days during pregnancy, never heavily1.00 --Mother drank 11-35 days, never heavily 0.91 0.43-1.95Mother drank 36+ days, never heavily 0.17 0.02-1.17Mother drank heavily, 1-10 days 0.38 0.05-2.69Mother drank heavily, 11+ days 1.29 0.29-5.80Maternal AUD, smoking during pregnancy, and offspring conduct problemsKnopik et al., in preparation

MARC project 4: Australian children of alcoholic female twins

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MARC project 4: Australian children of alcoholic female twins

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