Dataset Information

Parent-offspring transmission of drug abuse and alcohol use disorder: Application of the multiple parenting relationships design.

ABSTRACT: With complete genealogical and cohabitation information, new genetic-epidemiological designs can be developed to clarify causes of parent-offspring transmission. We propose the Multiple Parenting Relationships (MPR) Design and apply it to drug abuse (DA) and alcohol use disorder (AUD). Using national Swedish registries, we identified four kinds of informative parents with multiple children with whom they had different genetic and/or rearing relationships. These types had children for whom they provided: (a) genes (G) plus rearing (R), G only and R only; (b) G?+?R and G only; (c) G only and R only; and (d) G?+?R and R only. We identified DA and AUD cases from national registries in over 475,000 informative parent-offspring pairs. Controlling for parental resemblance for DA or AUD, all estimates were statistically homogeneous across family types. The weighted average tetrachoric correlation (SE) for DA for G?+?R, R only and G only relationships were, respectively, +0.21 (0.01), +0.10 (0.02), and +0.16 (0.02). Parallel results for AUD were +0.16 (0.01), +0.04 (0.02), and +0.14 (0.01). Analyses within families with affected parents showed significantly higher disorder risks in offspring with a G?+?R versus an R only relationship. The MPR design is complementary to other methods, especially adoption and triparental designs, in clarifying the sources of cross-generational transmission. Consistent with results from these other designs applied to the Swedish population, we find that for DA and AUD, parent-offspring resemblance was strongest for G?+?R relationships, intermediate for G only relationships and weakest but significant for R only relationships.

SUBMITTER: Kendler KS

PROVIDER: S-EPMC6534277 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Parent-offspring transmission of drug abuse and alcohol use disorder: Application of the multiple parenting relationships design.

Kendler Kenneth S KS Ohlsson Henrik H Sundquist Jan J Sundquist Kristina K

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20190301 4

With complete genealogical and cohabitation information, new genetic-epidemiological designs can be developed to clarify causes of parent-offspring transmission. We propose the Multiple Parenting Relationships (MPR) Design and apply it to drug abuse (DA) and alcohol use disorder (AUD). Using national Swedish registries, we identified four kinds of informative parents with multiple children with whom they had different genetic and/or rearing relationships. These types had children for whom they p ...[more]

PMID: 30821080

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Project description:AIMS:We tested whether parental alcohol use disorder (AUD) predicted adult offspring's likelihood of marriage and marriage to an AUD-affected spouse; whether effects differed as a function of the sex or number of affected parents; and whether they were robust to confounders. DESIGN:Sex-stratified Cox and logistic regression models. SETTING:Sweden. PARTICIPANTS:A total of 1?171?070 individuals (51.40% male) born 1965-75. MEASUREMENTS:Obtained from legal, medical and pharmacy registries. Predictor was parent AUD. Outcomes were marriage and spouse AUD. Adjustments included offspring birth year and AUD; and parental education, marriage, divorce, criminal behavior and drug abuse. FINDINGS:Male and female offspring of AUD-affected parents were more likely to marry at younger ages (< 25), illustrative unadjusted hazard ratio (HR)age 20 = 1.22 (1.17, 1.28) and 1.34 (1.20, 1.39) and were less likely to marry at older ages (> 25), HRage 30 = 0.79 (0.78, 0.81) and 0.82 (0.81, 0.84). Parental AUD was associated with higher odds of having an affected spouse for males and females, odds ratio (OR) = 1.47 (1.38, 1.57) and 1.63 (1.56, 1.70). Effects were more pronounced for those with two versus one AUD-affected parent and adjustments attenuated effects negligibly. Daughters of affected mothers (versus fathers) were more likely to have AUD-affected husbands, OR = 1.68 (1.54, 1.84) versus 1.56 (1.48, 1.64), while there was no difference in sons. CONCLUSIONS:In Sweden, parental alcohol use disorder (AUD) is associated with a higher probability of marriage at younger ages, a lower probability of marriage at older ages and a higher likelihood of marriage to an affected spouse compared with no parental AUD. Most of these effects become stronger when the number of AUD-affected parents increases from one to two, and most effects hold after controlling for parents' socio-economic status, marital history, other externalizing disorders and offspring's own AUD status. Daughters of affected mothers are more likely to have an affected spouse.

Project description:BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder sharing genetic risk factors with other common psychiatric disorders. However, intergenerational recurrence patterns of ADHD from parents to sons and daughters are not known. We aimed to examine the risk of ADHD in offspring of parents with ADHD and parents with other psychiatric disorders by parental and offspring sex, using parents without the specific disorders as comparison.MethodsIn a generation study linking data from several population-based registries, all Norwegians born 1967-2011 (n = 2,486,088; Medical Birth Registry of Norway) and their parents were followed to 2015. To estimate intergenerational recurrence risk, we calculated prevalence differences (PD) and the relative risk (RR) of ADHD in offspring by parental ADHD, bipolar disorder (BD), schizophrenia spectrum disorder (SCZ), major depression (MDD), all by parental and offspring sex.ResultsThe absolute prevalence of ADHD in offspring of parents with ADHD was very high, especially in sons of two affected parents (41.5% and 25.1% in sons and daughters, respectively), and far higher than in offspring of parents with BD, SCZ or MDD. Intergenerational recurrence risks were higher for maternal than paternal ADHD (RRmaternal 8.4, 95% confidence interval (CI) 8.2-8.6 vs. RRpaternal 6.2, 6.0-6.4) and this was also true on the absolute scale (PDmaternal 21.1% (20.5-21.7) vs. PDpaternal 14.8% (14.3-15.4)). RRs were higher in daughters, while PDs higher in sons. Parental SCZ, BD and MDD were associated with an approximately doubled risk of offspring ADHD compared to parents without the respective disorders, and estimates did not differ significantly between daughters and sons.ConclusionsThe intergenerational recurrence risks of ADHD were high and higher from mothers with ADHD than fathers with ADHD. Other parental psychiatric disorders also conferred increased risk of offspring ADHD, but far lower, indicating a sex- and diagnosis-specific intergenerational recurrence risk in parents with ADHD.

Dataset Information

Parent-offspring transmission of drug abuse and alcohol use disorder: Application of the multiple parenting relationships design.

Publications

Parent-offspring transmission of drug abuse and alcohol use disorder: Application of the multiple parenting relationships design.

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