Maternal half-sibling families with discordant fathers: A contrastive design assessing cross-generational paternal genetic transmission of alcohol use disorder, drug abuse and major depression

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TY - JOUR

T1 - Maternal half-sibling families with discordant fathers

T2 - A contrastive design assessing cross-generational paternal genetic transmission of alcohol use disorder, drug abuse and major depression

AU - Kendler, Kenneth S.

AU - Ohlsson, Henrik

AU - Sundquist, Jan

AU - Sundquist, Kristina

PY - 2019

Y1 - 2019

N2 - BackgroundWe introduce and apply an elegant, contrastive genetic-epidemiological design - Maternal Half-Sibling Families with Discordant Fathers - to clarify cross-generational transmission of genetic risk to alcohol use disorder (AUD), drug abuse (DA) and major depression (MD).MethodUsing Swedish national registries, we identified 73 108 eligible pairs of reared together maternal half-siblings and selected those whose biological fathers were discordant for AUD, DA and MD, and had minimal contact with the affected father. We examined differences in outcome in half-siblings with an affected v. unaffected father.ResultsFor AUD, DA and MD, the HR (95% confidence intervals) for the offspring of affected v. unaffected fathers were, respectively, 1.72 (1.61; 1.84), 1.55 (1.41; 1.70) and 1.51 (1.40; 1.64). Paternal DA and AUD, but not MD, predicted risk in offspring for attention deficit hyperactivity disorder, conduct disorder, and poor educational performance and attainment. Offspring of affected v. unaffected fathers had poorer pregnancy outcomes, with the effect strongest for DA and weakest for MD. A range of potential biases and confounders were examined and were not found to alter these findings substantially.ConclusionReared together maternal half-siblings differ in their paternal genetic endowment, sharing the same mother, family, school and community. They can help clarify the nature of paternal genetic effects and produce results consistent with other designs. Paternal genetic risk for DA and AUD have effects on offspring educational achievement, child and adult psychopathology, and possibly prenatal development. The impact of paternal genetic risk for MD is narrower in scope.

AB - BackgroundWe introduce and apply an elegant, contrastive genetic-epidemiological design - Maternal Half-Sibling Families with Discordant Fathers - to clarify cross-generational transmission of genetic risk to alcohol use disorder (AUD), drug abuse (DA) and major depression (MD).MethodUsing Swedish national registries, we identified 73 108 eligible pairs of reared together maternal half-siblings and selected those whose biological fathers were discordant for AUD, DA and MD, and had minimal contact with the affected father. We examined differences in outcome in half-siblings with an affected v. unaffected father.ResultsFor AUD, DA and MD, the HR (95% confidence intervals) for the offspring of affected v. unaffected fathers were, respectively, 1.72 (1.61; 1.84), 1.55 (1.41; 1.70) and 1.51 (1.40; 1.64). Paternal DA and AUD, but not MD, predicted risk in offspring for attention deficit hyperactivity disorder, conduct disorder, and poor educational performance and attainment. Offspring of affected v. unaffected fathers had poorer pregnancy outcomes, with the effect strongest for DA and weakest for MD. A range of potential biases and confounders were examined and were not found to alter these findings substantially.ConclusionReared together maternal half-siblings differ in their paternal genetic endowment, sharing the same mother, family, school and community. They can help clarify the nature of paternal genetic effects and produce results consistent with other designs. Paternal genetic risk for DA and AUD have effects on offspring educational achievement, child and adult psychopathology, and possibly prenatal development. The impact of paternal genetic risk for MD is narrower in scope.

KW - Alcohol use disorder

KW - Depression

KW - drug abuse

KW - genetic epidemiology

U2 - 10.1017/S0033291719000874

DO - 10.1017/S0033291719000874

M3 - Article

C2 - 30992087

AN - SCOPUS:85065253711

JO - Psychological Medicine

JF - Psychological Medicine

SN - 1469-8978

ER -