Psychological Medicine

Original Articles

Clinical features of drug abuse that reflect genetic risk

K. S. Kendlera1a2a3 c1, H. Ohlssona4, K. Sundquista4a5 and J. Sundquista4a5

a1 Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

a2 Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

a3 Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA

a4 Center for Primary Health Care Research, Lund University, Malmö, Sweden

a5 Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA


Background Drug abuse (DA) is a clinically heterogeneous syndrome. Can we, in a large epidemiological sample, identify clinical features of DA cases that index genetic risk?

Method Using registration in medical, legal or pharmacy records, we identified four kinds of relative pairs (n = 935 854) starting with a proband with DA: monozygotic co-twins; full siblings; half-siblings; and cousins. Using linear hazard regression, we examined the interaction between three clinical features of DA in the proband and risk for DA in these four relative pairs, ordered by degree of genetic relationship.

Results Increased risk for DA in relatives was robustly predicted by early age at first registration, total number of registrations, and ascertainment in the criminal versus the medical or pharmacy registry. In multivariate models, all three of these variables remained significant and in aggregate strongly predicted DA risk in relatives. The risk for DA in siblings of DA probands in the highest decile of genetic risk predicted by our three indices was more than twice as great as that predicted in siblings of probands in the lowest decile of risk.

Conclusions In an epidemiological sample, genetic risk for DA can be substantially indexed by simple clinical and historical variables.

(Received August 06 2013)

(Revised November 20 2013)

(Accepted December 16 2013)

(Online publication January 24 2014)

Key words

  • Age at first registration;
  • drug abuse;
  • genetic risk;
  • Sweden


c1 Address for correspondence: K. S. Kendler, M.D., Virginia Institute for Psychiatric and Behavioral Genetics of VCU, Box 980126, Richmond, VA 23298-0126, USA. (Email: