Genetics may not be the only factor

Genetics may not be the only factor at play in the development ofsynesthesia. Smilek et al. [11] reported a pair of discordant femalemonozygotic twins; one experienced synesthesia and one did not[11]. The authors hypothesized that the discordance was due toeither X chromosome inactivation or an epigenetic event. Thesefindings indicate that genetic inheritance alone may not offer a fullexplanation of synesthesia.Our study seeks to understand the genetic contribution tosynesthesia by examining both monozygotic and dizygotic twins,recruiting a large cohort of twin pairs for the analysis, and usingrigorous phenotyping. We compare the concordance rates of synes-thesia in monozygotic and dizygotic twin pairs to estimate theextent to which epigenetic or environmental factors may play arole in the development of synesthesia.2. MethodsMany varieties of synesthesia have been reported; for this studywe focus specifically on colored-sequence synesthesia (CSS) inwhich sequences such as letters, numbers, days of the week, andmonths trigger color perception. Our previous analysis of 3194colored-sequence synesthetes revealed that having synestheticcolor associations for one type of sequence (e.g., letters) givesa ∼79% likelihood of having color associations for another typeof sequence (e.g. numbers), but only chance likelihood of havinganother form of synesthesia [12], indicating that CSS is a distinctsubtype of synesthesia that may result from a distinct mecha-nism. Motivated by this finding, our prior genetics research hasalso focused on CSS [7].For phenotyping, we used the Synesthesia Battery, a stan-dardized online test that distinguishes synesthetes from non-synesthetes [13]. The Synesthesia Battery presents participantswith graphemes (A–Z, 0–9), months (January–December) or week-days (Monday–Sunday). All stimuli are presented in random orderthree times each. Participants are asked to select the synestheti-cally associated color for each stimulus from a color palette of 16.7million colors. The color choices for each grapheme are analyzed forconsistency across the three trials within the session (for example,choosing the same color of red each time a participant saw the letterA; for full details, see [13]). Non-synesthetic controls have low con-sistency in associating the colors to the stimuli, while synesthetesdisplay high consistency in their repeated choices.From the pool of Synesthesia Battery participants, we contacted151 individuals who completed the grapheme-color portion of thetest and reported having a twin in an optional text field. 38 twinpairs (76 individuals) gave consent to participate in the study. Weconducted interviews with interested twin pairs online and overthe phone to determine zygosity (via self-report), concordance,and demographic information (including whether the pair wasreared together – which was true for all pairs in the sample). All twins reporting synesthesia or uncertainty about having synesthe-sia were instructed to take the Synesthesia Battery to verify theirphenotype