Clinical features of drug abuse that reflect genetic risk.
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?


METHODS
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.
Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University,Richmond, VA,USA.
K S
KS
Kendler
Center for Primary Health Care Research,Lund University,Malmö,Sweden.
H
H
Ohlsson
Center for Primary Health Care Research,Lund University,Malmö,Sweden.
K
K
Sundquist
Center for Primary Health Care Research,Lund University,Malmö,Sweden.
J
J
Sundquist
D000328:Adult; D017668:Age of Onset; D004200:Diseases in Twins / Q000453:epidemiology / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries / Q000706:statistics & numerical data*; D012306:Risk; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult