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18 Heritability of episodic memory as a prerequisite for genetic studies During the last 4 decades animal studies in both invertebrates and verte- brates have identified genes and signaling molecules important for mem­ ory1-5 . From this work it appears that many of the memory-related mole- cular mechanisms are conserved across species. However, it has been largely unknown whether these molecular pathways are also involved in human memory. The major reason for the lack of translation of the ani- mal findings to humans is that pharmacological manipulation of many of these signaling molecules in humans is not feasible either due to safety issues or lack of pharmacologic specificity. Recent advances in the iden- tification of genetic variants in the human genome opened, however, new avenues for the examination of complex phenotypes such as human mem­ ory. One of the major neurocognitive systems that enables conscious ­recollection of past experiences (e.g., autobiographical episodes, learned material) along with their spatial and temporal contexts is termed episod­ ic memory6 (see Glossary). From a genetic standpoint, episodic memory can be defined as a genetically complex behavioral trait with substantial heritability estimates (i.e., genetic factors account for a significant pro- portion of this phenotype’s variance). Several twin studies report herita- bility values between 30 % and 60 %7-13 , indicating that naturally occur- ring genetic variations have an important impact on this cognitive ability. The majority of these studies treat episodic memory as a single, unified construct without breaking it down in its underlying phenotypic struc- ture, which is characterized, for example, by temporally distinct phases as assessed by short-delay recall and long-delay recall. However, recent empiric evidence from twin studies14 revealed both overlapping and dis- tinct genetic influences on these temporal components of episodic mem­ ory. In brief, twin studies in non-clinical populations clearly demon­- strate the genome’s importance for this neurocognitive trait. The signi­- ficant proportion of phenotypic variability in episodic memory that is attributable to heritable factors is a prerequisite and a starting point for targeted genetic studies aimed at identifying specific molecules and ­pathways thereof related to specific components of human episodic mem­ ory. Additional features of episodic memory, which render it suitable for human genetic analysis include: