Received: 15 May 2017
Accepted: 13 November 2017
Familial transmission of externalizing syndromes
in extended Swedish families
Kenneth S. Kendler MD
Henrik Ohlsson PhD
Jan Sundquist MD, PhD
Kristina Sundquist MD, PhD
Virginia Institute for Psychiatric and
Behavioral Genetics, Virginia Commonwealth
University, Richmond, Virginia
Department of Psychiatry, Virginia
Commonwealth University, Richmond, Virginia
Center for Primary Health Care Research,
Lund University, Malmö, Sweden
Kenneth S. Kendler, MD, Virginia Institute for
Psychiatric and Behavioral Genetics of VCU,
Box 980126, Richmond, VA 23298-0126.
National Institute on Drug Abuse,
Grant number: R01DA030005; National
Institute on Alcohol Abuse and Alcoholism,
Grant number: R01AA023534
Risk for criminal behavior (CB), alcohol use disorder (AUD), and drug abuse (DA) are
known to be familial. We know less about their transmission across three generations.
We examined 844,109 probands born in Sweden 1980–1990, their parents, aunts/
uncles, and grandparents for registration in population-based registers for CB, AUD,
and DA. Mean tetrachoric relative-proband correlations (95% CIs) were highest for DA
(+0.24, 0.24–0.25), followed by CB (+0.23,0.22–0.23) and AUD (+0.17, 0.16–0.17).
AUD and CB were relatively stably transmitted across generations, while DA
resemblance among relatives was stronger in the younger generations. For all three
syndromes, male-male transmission was modestly stronger than female–female.
Cross-sex transmission was significantly weaker than same-sex transmission for DA
and CB but not AUD. Risk to probands with only an affected grandparent or aunt/uncle
were increased 50–60% for CB and AUD, and 70–100% for DA. Parallel figures for
affected parents only and parents + grandparent or aunt/uncle were 2–3-fold and 4–5-
fold for CB and AUD, and 4–5-fold and 6–7-fold for DA. CB, AUD, and DA are all
substantially familial in the Swedish population with the transmission across three
generations stable for CB and AUD but not DA. Modest quantitative sex effects are
seen in the familial transmission of CB, AUD, and DA, and qualitative sex effects for CB
and DA. Risk prediction in offspring is orderly with affection status in grandparental and
avuncular relationships adding appreciably to that from the parental generation.
alcohol use disorder, crime, drug abuse, familial transmission, grandparents, parents, sex
Criminal behavior (CB), Alcohol Use Disorder (AUD), and Drug Abuse
(DA) are all strongly transmitted within families (Besemer, 2012; Cotton,
1979; Merikangas et al., 1998). Twin and adoption studies suggest that
while a substantial proportion of this transmission of these syndromes
results from genetic factors, familial environmental effects also contrib-
ute (Kendler et al., 2012, 2014; Kendler, Ji, et al., 2015; Kendler, Lonn,
et al., 2016; Verhulst, Neale, & Kendler, 2015). A limitation of the
systematic studies of thefamilial transmission of AUD and DA is that they
have almost exclusively examined only nuclear families—looking at
resemblance of twins or siblings, or more rarely parents and children.
Only with CB is there a substantial literature exploring the transmission
across three generations (Besemer, 2012; Besemer, Axelsson, Sarnecki,
2016; Junger, Greene, Schipper, Hesper, & Estourgie, 2013; Putkonen,
Ryynanen, Eronen, & Tiihonen, 2007; van de Weijer, Bijleveld, &
Blokland, 2014). Avuncular relationships—between uncles/aunts and
their nieces and nephews—have been even more infrequently examined
because such data is rarely available.
Where the work was performed: Analyses—Malmö Sweden; Writing—Richmond USA and
© 2017 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/ajmgb Am J Med Genet. 2018;177B:308–318.