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.

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.

Publication date: Apr 01, 2020

We 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).

Using 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.

For 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.

Reared 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.

Concepts Keywords
Alcohol Depression drug abuse
AUD Family
Conduct Disorder Fatherhood
Confidence Intervals Kinship and descent
Cross Sibling
DA Human behavior
Depression Aud
Drug Abuse Anthropology
Endowment Humans
Epidemiological Medical genetics
Genetic RTT
Pregnancy
Prenatal Development
Psychopathology
Swedish

Semantics

Type Source Name
disease MESH alcohol use disorder
disease MESH drug abuse
disease MESH depression
disease MESH attention deficit hyperactivity disorder
disease MESH conduct disorder
disease MESH pregnancy outcomes
disease MESH community
disease MESH educational achievement
disease MESH development

Original Article

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