Measured gene-by-environment interaction in relation to attention-deficit/hyperactivity disorder.
OBJECTIVE
To summarize and evaluate the state of knowledge regarding the role of measured gene-by-environment interactions in relation to attention-deficit/hyperactivity disorder.


METHODS
A selective review of methodologic issues was followed by a systematic search for relevant articles on measured gene-by-environment interactions; the search yielded 16 studies, which are discussed in qualitative fashion.


RESULTS
Relatively consistent evidence points to the interaction of genotype with psychosocial factors in the development of attention-deficit/hyperactivity disorder. The next step is to identify the mechanisms on the environment side and the gene combinations on the genetic side accounting for this effect. In contrast, evidence for gene-by-environment interactions involving pre- and perinatal risk factors is generally negative or unreplicated. The aggregate effect size for psychosocial interaction with genotype is more than double that for the interaction of pre- and perinatal risks with genotype. Only a small fraction of candidate environments and gene markers has been studied, and multivariate methods to integrate multiple gene or environment markers have yet to be implemented.


CONCLUSIONS
Gene-by-environment interaction appears likely to prove fruitful in understanding the etiology of attention-deficit/hyperactivity disorder. Findings to date already suggest new avenues of investigation particularly involving psychosocial mechanisms and their interplay with genotype. Further pursuit of theoretically promising leads is recommended.
Nigg
Joel
J
Department of Psychiatry, Oregon Health and Science University, 3181 Sam Jackson Park Road, Portland, OR 97239, USA. niggj@ohsu.edu
Nikolas
Molly
M
Burt
S Alexandra
SA
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology*; D002648:Child; D002874:Chromosome Mapping; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D016487:Parenting / Q000523:psychology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D012931:Social Environment
D005819:Genetic Markers