J Neural Transm (2001) 108: 115–121 No association between dopamine D2 receptor gene (DRD2) and human intelligence H. W. Moises 1 , R. M. Frieboes 1 , P. Spelzhaus 1 , L. Yang 1 , M. Köhnke 1 , O. Herden-Kirchhoff 1 , P. Vetter 1 , J. Neppert 2 , and I. I. Gottesman 3 1 Molecular Genetics Laboratory, Department of Psychiatry, and 2 Institute for Blood Transfusion, Kiel University Hospital, Kiel, Federal Republic of Germany 3 Department of Psychology, University of Virginia, Charlottesville, VA, USA Received March 13, 2000; accepted July 27, 2000 Summary. Significantly diminished intellectual functioning, as indicated by appropriately administered IQ tests with scores below 70, is a frequent mental handicap leading to severe social disadvantages and serves as a paradigm for molecular genetic research of complex disorders and traits due to its multi- tude of known and unknown, genetic as well as environmental causes. Since the number of confounding variables is expected to be considerably reduced in the normal population at the opposite ends of the IQ distribution, we employed a contrast of extremes approach by comparing adults of high (N = 71) and average IQ (N = 78) in association studies to search for genes involved in the multigenic forms of familial mental retardation. The dopamine D2 receptor gene (DRD2) was chosen as a candidate gene for general cogni- tive ability (g) since it has been found to be associated with visuospatial ability which in turn is highly correlated with g. Confirming two similar studies in children, however, no significant differences were obtained. Given three nega- tive studies, the DRD2 gene is unlikely to pay a major role in g. Keywords: Alleles, biological markers, cognition/physiology, dopamine/ genetics/physiology, DNA/analysis, genotype, human, intelligence tests, polymorphism (genetics), quantitative trait. Introduction Mental retardation is a frequent mental handicap leading to severe social disadvantages. Cultural evolution, with its replacement of simple human work by machines and its increasing emphasis on education and cognitive abilities for solving the increasingly complex problems of human society, will further lead to the social decline of individuals suffering from mild to severe mental