Musikaalisuuden genetiikkaa ja genomiikkaa

Most people have the capacity for music perception and production, but the degree of music competency varies between individuals. In this thesis, I studied abilities to identify pitch, tone duration and sound patterns with Karma s test for auditory structuring (KMT), and Seashore s tests for time (ST) and pitch (SP). These abilities can be considered as basic components of musicality. Additionally, I studied self-reported musical activities, especially composing and arranging. Musical ability is a diverse phenotype that includes both acquired and innate abilities. Earlier studies have shown that genetic component affects musical traits; here, heritability was estimated as 21-68%. Genetic predisposition of musical abilities was studied in family material (N=915) using linkage and linkage disequilibrium analyses. The best association for musical aptitude (KMT, SP and ST) was obtained at 3q21.3 near GATA2 and the best linkage at 4p14 adjacent to PCDH7. For musically experienced individuals without creative activity in music, linkage was found at 18q21. Interestingly, regions near 4q22.1 and 16p12.3 were linked with multiple musical traits. The genes within the resulting regions showed enrichment of inner ear development, schizophrenia and the long-term depression pathway, which is a molecular pathway important in learning and memory. Using three selection signature methods, FST, haploPS and XP-EHH, over 100 candidate genomic regions were detected to be under positive selection in individuals with high music test scores in the music tests. Enrichment analysis pointed to the development of the inner ear, corresponding to the enrichment results from the musical aptitude linkage analysis, even though there were no common regions between these two studies. The fourth part of this thesis integrates our musical ability gene mapping results with other music-related studies, including also animal model studies. A convergent genomics approach ranked EGR1, cortisol, FOS and FOXP2 as the most prominent molecules that affect musical abilities. The best 40 genes showed enrichment of cognition. Previous studies have shown that musical abilities share a common background with cognitive abilities, such as intelligence, and this study is the first to suggest the associated molecules. In conclusion, with these studies, I suggest many new genes and pathways to be associated with musical traits. The genetic predisposition for music is affected by a large number of genes of which only a few have been identified. Musical abilities were linked to multiple different chromosomes of which the 4q22 region is especially interesting. We made a literary survey combining information of molecules related to musical traits that can be used to evaluate genomics results in the future.Musiikin on todettu vaikuttavan ihmisiin sekä muihin eläimiin: musiikin kuuntelu ja tuottaminen muuttavat hormonituotantoa, nopeuttavat paranemista sekä muuttavat aivoja jopa pysyvästi. Musiikki vaikuttaa lähes kaikkiin, mutta yksilöiden välillä on eroja: kaikki eivät kasva musiikin ihmelapsiksi ja joillekin sävelen muistaminen on helpompaa kuin toisille. Väitöskirjatyöni aiheena on selvittää musikaalisuuden geneettistä taustaa, sitä yksilöiden välistä eroa, joka antaa meille erilaiset lähtökohdat musiikin harjoittamiseen. Musikaalisuus sisältää paljon erilaisia ominaisuuksia, joista tässä työssäni keskityn kuullun musiikin erotteluun perustuviin Karman ja Seashoren testeihin, jotka mittaavat sävelkorkeuden, -pituuden ja rakenteiden erottelua, sekä musikaalisen luovuuden ominaisuuksiin, erityisesti säveltämiseen ja sovittamiseen. Näiden ominaisuuksien heritabiliteetiksi, eli geneettiseksi osuudeksi yksilöiden välisistä eroista, arvioitiin 21-68%. Väitöskirjan osatöissä käytimme aineistona suomalaisia sukuja, joiden avulla tunnistimme musikaalisuuteen vaikuttavia genomin alueita. Parhaat tulokset löytyivät kromosomeista 3q21.3, 4p14 ja 18q21. Lisäksi useampaan ominaisuuteen kytkeytyivät alueet kromosomeista 4 ja 16. Positiivisen valinnan merkkejä tunnistimme yli 100 sellaiselta perimän alueelta, jotka ovat ominaisia musikaalisuustesteissä pärjääville. Tunnistetuilta alueilta löytyneet geenit liittyivät erityisesti sisäkorvan kehitykseen, skitsofreniaan sekä oppimiseen ja muistiin liittyvään LTD-reaktioreittiin. Viimeisessä osatyössä yhdistimme aiemmat osatyöt muihin musikaalisuuden julkaistuihin geeni- ja molekyylituloksiin, kuten linnunlauluun ja musiikkialtistukseen liitettyihin geeneihin. Konvergoivan genomiikan menetelmällä arvotimme todennäköisimmiksi musikaalisuuteen vaikuttaviksi molekyyleiksi EGR1-, FOS- ja FOXP2-geenit sekä kortisolin. Parhaiden 40 molekyylin joukossa oli rikastuneina erityisesti kognitiivisiin kykyihin liittyviä geenejä. Aiemman tutkimuksen valossa tiedetään kognitiivisilla kyvyillä ja musikaalisuudella olevan osittain yhteinen tausta, mutta yhteisiä geenejä ei ole tunnettu. Musikaalisuus on monitekijäinen ominaisuus, johon vaikuttavat sekä synnynnäiset kyvyt että opitut taidot. Oletettavaa on, että musiikkiin liittyy satoja, jopa tuhansia geenejä. Tässäkin tutkimuksessa näytimme musikaalisuuden kytkeytyvän useille genomin alueille ja keräsimme kirjallisuudesta musiikkiin liittyviä tuloksia, jotka osoittavat tuhansiin eri geeneihin. Erityisen kiinnostava on kromosomin 4 alue, joka on löydetty monessa eri tutkimuksessa eri musiikin ominaisuuksilla

Environmental Sensitivity: A Multi-Domain Investigation of its Development in Infancy

Highly sensitive individuals are thought to be disproportionately susceptible to both the risk engendering and development enhancing elements of their environment. If this is so, it seems necessary to hold that sensitivity is a unitary construct, in which markers of sensitivity to stimuli at neural, autonomic, and behavioural levels of analysis moderate the relationship between early social environments and outcomes, for better as well as for worse. The trait of environmental sensitivity (ES) is theorised, through conditional adaptation to enable resource exploitation or risk survival in the developmental context. This thesis tests four main hypotheses: that measures of ES at different levels of analysis would covary at 6-months and would be evoked by positive and negative stimuli; whether associations between measures at 6-months would endure by 12-months; that indices of sensitivity at 12-months would associate with measures indexing the quality of the developmental environment; that measures indexing ES would moderate the relationship between the environment and outcomes. Neural, autonomic, and behavioural indices of ES were measured in N82 infants at 6-months and 12-months, while concurrently collecting data on the wellbeing and socioeconomic status (SES) of their parents. Levels of infant self-regulation and sustained attention were assessed at 12-months. Associations between visual and auditory neural sensitivity were found at 6-months but not 12-months. Likewise, measures of positive and negative behavioural reactivity correlated at 6-months but not 12-months. Maternal SES moderated the relationship between negative reactivity at 6-months and positive reactivity at 12-months such that negatively reactive 6-months infants from high SES households were more positively reactive at 12-months. Baseline RSA at 6-months moderated the relationship between maternal anxiety and 12-months self-regulation but was marginally non-significant. The results are interpreted from the perspective of theories and concepts that have been integrated into a single overarching meta framework of Environmental Sensitivity

Attention Restraint, Working Memory Capacity, and Mind Wandering: Do Emotional Valence or Intentionality Matter?

Attention restraint appears to mediate the relationship between working memory capacity (WMC) and mind wandering (Kane et al., 2016). Prior work has identifed two dimensions of mind wandering—emotional valence and intentionality. However, less is known about how WMC and attention restraint correlate with these dimensions. Te current study examined the relationship between WMC, attention restraint, and mind wandering by emotional valence and intentionality. A confrmatory factor analysis demonstrated that WMC and attention restraint were strongly correlated, but only attention restraint was related to overall mind wandering, consistent with prior fndings. However, when examining the emotional valence of mind wandering, attention restraint and WMC were related to negatively and positively valenced, but not neutral, mind wandering. Attention restraint was also related to intentional but not unintentional mind wandering. Tese results suggest that WMC and attention restraint predict some, but not all, types of mind wandering