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Cloettapreis_2013_Nr_41

25 cal methods accounting for gene-gene interactions supports the notion that rare combinations of common variants significantly account for this trait’s variability and heritability. Therefore, the study of the genetic ­architecture of episodic memory will require a statistical and systems biology framework that accounts for the complexity of the interacting functional molecular networks. The current approaches (e.g., set-associ- ation42 , set-based tests43 , multifactor dimensionality reduction44 , gene set enrichment analysis45 , to name just a few) are clearly a very good start. However, as more and more methods will become available, study de- signs based on multidisciplinary research frameworks and focusing on replication of the identified complex genetic structures will prove in­ valuable for the robust and reliable discovery of parts of the genetic ­underpinnings of episodic memory. Phenotypic complexity Episodic memory refers to memory for past experiences (e.g., autobio- graphical episodes, learned material), which includes information about the content of the experience and the spatial and temporal context in which it occurred46, 47 . It is important to realize that in terms of neurobio- logical underpinnings, episodic memory performance may be subserved by distinct molecular profiles, depending on the specific episodic memo- ry task used for quantifying performance. For example, the BDNF ­Val66Met polymorphism has been shown to be associated with delayed­ recall from stories of the Wechsler Memory Scale, revised version, but not with delayed recall of a word list taken from the California Verbal Learning Test16 – yet both tasks are referred to as episodic memory tasks. Furthermore, it is well known that emotionally arousing information is better stored into memory than neutral information and that this phe­ nomenon depends on the activation of noradrenergic transmission48, 49 . ­Consequently, it has been shown that a functional deletion variant of ADRA2B, the gene encoding the α2b-adrenergic receptor, is related to differential episodic memory performance for emotionally arousing ­pictures, but not for neutral pictures50 . Furthermore, it is important to note that several ­factors, which are not considered to belong to episodic ­memory, such as ­motivation, attention or concentration can have a large impact on per­formance in episodic memory tasks. Thus, in behavioral

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