Widespread Evidence for Non-Additive Genetic Variation in Cloninger’s and Eysenck’s Personality Dimensions Using a Twin Plus Sibling Design Matthew C. Keller, 1,4 William L. Coventry, 2 Andrew C. Heath, 3 and Nicholas G. Martin 2 Received 24 Sep. 2004—Final 20 May 2005 Studies using the classical twin design often conclude that most genetic variation underlying personality is additive in nature. However, studies analyzing only twins are very limited in their ability to detect non-additive genetic variation and are unable to detect sources of variation unique to twins, which can mask non-additive genetic variation. The current study assessed 9672 MZ and DZ twin individuals and 3241 of their siblings to investigate the environmental and genetic architecture underlying eight dimensions of personality: four from Eysenck’s Personality Questionnaire and four from Cloninger’s Temperament and Character Inventory. Broad-sense heritability estimates from best-fitting models were two to three times greater than the narrow-sense heritability estimates for Harm Avoidance, Novelty Seeking, Reward Dependence, Persistence, Extraversion, and Neuroticism. This genetic non-additivity could be due to dominance, additive-by-additive epistasis, or to additive genetic effects combined with higher-order epistasis. Environmental effects unique to twins were detected for both Lie and Psychoticism but accounted for little overall variation. Our results illustrate the increased sensitivity afforded by extending the classical twin design to include siblings, and may provide clues to the evolutionary origins of genetic variation underlying personality. KEY WORDS: Behavior genetics; dominance; epistasis; non-additive genetic variation; personality. INTRODUCTION One of the most consistent findings in modern personality research has been that unique experiences and genes play important roles in the development of personality differences while shared familial envi- ronmental effects are much less influential. Support for this comes from studies of adoptees and their families (e.g., Loehlin et al., 1985), separated twins (e.g., Bouchard et al., 1990), twins reared together (e.g., Eaves et al., 1989), and twins along with other family members (e.g., Eaves et al., 1999). While each methodology has potential confounds individually, most of these confounds do not overlap. Taken together these studies suggest that genetic differences account for one-third to half of the variation in studied personality dimensions while shared envi- ronments account for little, if any, of this variation. Beyond these broad conclusions, there has been little resolving power to describe the genetic archi- tecture underlying personality. Most research on the genetics of personality has come from classical twin studies, which rely on the comparison between MZ (monozygotic, identical) and DZ (dizygotic, fraternal) twins reared together. These studies typically con- clude that most of the genetic variation underlying personality is additive in nature; non-additive genetic 1 Center for Society and Genetics (UCLA), University of Cali- fornia, Los Angeles, USA. 2 Queensland Institute of Medical Research, Brisbane, Australia. 3 Department of Psychiatry, Washington University, St. Louis, USA. 4 To whom Correspondence should be addressed at University of California, Center for Society and Genetics (UCLA), 1339 Murphy Hall, Los Angeles, CA, 90095-1405, USA. e-mail: matthew.c.keller@gmail.com 707 0001-8244/05/1100-0707/0 Ó2005 Springer Science+Business Media, Inc. Behavior Genetics, Vol. 35, No. 6, November 2005 (Ó 2005) DOI: 10.1007/s10519-005-6041-7