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Developmental language impairments are neurodevelopmental disorders in which the acquisition of language, a task which children typically perform with ease, is hindered or fraught with difficulty. This work focuses on specific language impairment (SLI), a common and highly heritable language impairment in which language development is abnormal while other developmental domains are normal. Additionally, a case-study of a child with a broader linguistic and behavioural phenotype is also presented. The work described in this thesis includes both genetic and functional investigations which were aimed at identifying candidate genes for language impairment and provide insight into the genetic mechanisms that underlie language development. I performed a genome-wide association study of SLI which included child genotype effects, maternal genotype effects, parent-of-origin effects, and maternal-foetal interaction effects. This study found significant paternal parent-of-origin effects with the gene NOP9 on chromosome 14, and suggestive maternal parent-of-origin effects with a region on chromosome 5 which had previously been implicated in autism and ADHD. Case-control and quantitative association analyses of HLA genes and SLI identified several risk alleles and protective alleles. A case-control association analysis for related individuals which used an isolated population affected by SLI identified a non-synonymous coding variant in the gene NFXL1 which was significantly more frequent in affected individuals than in unaffected individuals. High-throughput sequencing of the coding regions of NFXL1 and LD blocks surrounding associated variants in ATP2C2, CMIP and CNTNAP2 (as reported in previous studies) identified novel or rare non-synonymous coding variants in NFXL1 and ATP2C2 in SLI families as well as intronic variants in all four genes that were significantly more frequent in SLI probands than in population controls. I describe a functional study of NFXL1 examining its expression in various brain regions, the presence of different splice variants across several tissues, its effect on genes it potentially interacts with, and the subcellular localisation of the protein. Finally, I present the case-study of a child with language impairment who had chromosomal rearrangements which spanned the location of FOXP2. I examine the potential influence the chromosomal rearrangements had on FOXP2 expression and describe a lincRNA gene which was disrupted by the chromosomal inversion. In conclusion, this work identified new candidate genes for language impairment, provided further support for the involvement of previously-identified candidate genes in SLI and contributed to the understanding of the molecular function of a newly-identified candidate gene for SLI.

Psychiatric genetics is a basic science field that has potential for practical application and effective translation. To date, translational frameworks utilized by this field have been linear (e.g., sequential) in nature, focusing on molecular genetic information. It is proposed that non-linear (e.g., socio-ecological) frameworks are a better way to immediately translate non-molecular genetic information. This dissertation explored the translation of psychiatric genetic information in two ways. First, a survey was sent to academic stakeholders to assess the state of the science regarding the translation of genetic information to the clinical care of mental health disorders. Findings from this indicate a translation-genetic competence gap whereby genetic knowledge reinforces linear frameworks and genetic competence is needed to achieve effective translation in this content area. Second, a new risk factor model for social anxiety was created that incorporated genetic, environmental, and neurophysiological risk factors (behavioral inhibition, parental bonding, emotion reactivity). Findings indicate that genetic etiology is more informative knowledge that can influence risk factor models and possibly prevention and intervention efforts for social anxiety. Overall this dissertation paves the way for examining the translational capacity of psychiatric genetics in a clinical setting. It constitutes the first examination of barriers to and a potential solution for the most effective translation of psychiatric genetic information.

1. Introduction This dissertation consists of six chapters that span a very diverse set of topics. Yet, it has two unifying themes, economics and biology, that tie it together. The first four chapters present the principal findings from a project that was initiated jointly with David Cesarini and Magnus Johannesson, and that applies the twin method from behavioral genetics to economics. The last two chapters instead use a simple regression framework and evidence from biological anthropology to investigate recent claims regarding the effects of child bearing and past slave trades. 2. Genes and economics There is a small, but rapidly growing, literature studying the genetic and environmental origins of economic behavior and outcomes (Bowles et al., 2005; Beauchamp et al., 2011). Until recently, this literature focused exclusively on outcomes, and in particular income. In chapters 1-4 we instead focus on economic behavior and decision-making. Previous behavioral genetic work outside the domains of economics has changed the way that we think about a number of behavioral traits. In this literature it is typically found that i) variation is heritable ii) genetic factors are more important than family environment iii) a large fraction of variation cannot be explained by neither genes nor family environment (Turkheimer, 2000; Plomin et al., 2009). However, compared to many other disciplines, and psychology in particular, economics is lagging behind. In fact, as recently as 2009 the leading text book in behavioral genetics described economics as "still essentially untouched by genetic research" (Plomin et al., 2009, p. 353). Hopefully, the chapters in this dissertation can help to improve on this somewhat unsatisfactory state of the art. Chapters 1 and 2 study economic decision-making in the laboratory using the twin method. More specifically, we study the ultimatum and dictator games alongside risky gambles, using same-sex twin pairs as our subject pool. Given a few additional assumptions, the fact that identical twins have, in expectation, a twice as high coefficient of genetic relatedness as fraternal twins implies that we can study the genetic and environmental contributions to variation in behavior by studying twin correlations in observed choices. Chapters 3 and 4 apply the same method to actual portfolio choices associated with a far-reaching pension reform, as well as to a set of standard behavioral anomalies. Taken together, these four chapters provide strong evidence in favor of the hypothesis that genes influence economic decision-making. Thus, economic behavior does not appear to be much different from other types of behavior. 3. Economics and history The last two chapters of the dissertation turn to the past, rather than genes, in an effort to evaluate recent findings regarding two important welfare outcomes. In chapter 5 we investigate Nunn’s (2008) claim that past slave trades had a negative impact on current economic performance in Africa. By extending the sample period back in time we demonstrate that this relationship was not significant in 1960. In addition, by applying Nunn’s method to an episode of large scale slave raiding in Italy, we demonstrate that there exists a similar negative relationship across Italian regions, although it becomes insignificant when geographical controls are included. Intriguingly, going back to 1960, the coefficient on slave raids for Italy also has a similar time trend to that for Africa. Taking these facts, and our reading of the historical and anthropological literature, which is much different from that of Nunn, into account we do not find much support for the hypothesis that the African slave trades had a negative impact on current economic performance. Finally, chapter 6 investigates the large and negative relationship between giving birth to a son, rather than a daughter, and maternal longevity that was documented in a Sami hunter-gatherer population from Finland (Helle et al., 2002). Using a substantially larger sample of pre-industrial Swedish Sami we find no evidence in favor of such a relationship. 4. Brasklapp Five of the chapters in this dissertation (Ch. 1-4 &amp; 6) are slightly altered versions of previously published papers (Wallace et al., 2007; Cesarini et al., 2009 a, b; 2010; 2011). Unfortunately, the fact that earlier versions of the chapters were prepared as separate articles for five different journals means that they can at times appear both repetitive, and in terms of notation and formatting, somewhat inconsistent. I apologize to the reader for these inconveniences. / <p>Diss. Stockholm :  Stockholm School of Economics, 2011. Introduction together with 6 papers</p>

Genetic and home chaos influences in early childhood have been independently associated with externalizing problems, characterized by inattentive, hyperactive, and aggressive behaviors. However, the Behavioral Genetics approach indicates that genetic and environmental influences, although independently effective, interact to produce behavior throughout development. Thus, this thesis uses two samples, the Early Growth and Development study (EGDS), n= 564, and the Avon Longitudinal Study of Parents and Children (ALSPAC), n= 8,952, and two genetically-sensitive approaches, a parent-child adoption approach and a polygenic scoring approach, to examine how genetic influences and home chaos interact in early childhood (age 3-4) to predict externalizing problems later in childhood (age 7). Results indicate that, although home chaos is correlated with later externalizing problems, the effect is reduced in the context of earlier externalizing, possibly suggesting that home chaos is most salient for concurrent, not later, externalizing problems. In addition, genetic influences were not predictive of externalizing problems in either study, nor was the interaction of home chaos and genetic influences. This pattern of results suggests that, although home chaos may be an important factor for concurrent externalizing problems, other factors, e.g., parenting style and prenatal risk, may be more salient than home chaos, especially in interaction with genetic effects. Further, failure to find genetic influence in this thesis suggest that accounting for the broad scope of genetic influences on complex traits like externalizing and the specific genetic risk for individual externalizing phenotypes is important in attempts to find genetic influence and interaction.

As mucopolissacaridoses (MPS) são um grupo de doenças metabólicas hereditárias causadas pela deficiência de enzimas lisossomais específicas, que causam alterações físicas e/ou comportamentais crônicas e progressivas. Um fenótipo comportamental é um padrão característico de observações motoras, cognitivas, linguísticas e sociais consistentemente associado a uma condição biológica. Tal fenótipo pode ser um transtorno mental ou outras características de comportamento não necessariamente associadas a transtornos. No caso específico das mucopolissacaridoses, embora haja diversos relatos na literatura sobre as altas taxas de ocorrência de problemas de comportamento na síndrome de Sanfilippo (MPS III), muito pouco é conhecido sobre as características comportamentais das outras entidades (MPS I, II, IV, VI e VII). Este trabalho pretendeu avaliar e descrever as alterações psiquiátricas encontradas em 22 pacientes com MPS atendidos em três serviços de genética clínica (4 MPS I, 5 MPS II, 1 MPS III, 4 MPS IV, 7 MPS VI, 1 MPS VII). As avaliações foram feitas através de instrumentos específicos, traduzidos e validados para nossa população, a saber: K-SADS PL, ATA, CARS, CGAS; e um instrumento traduzido, mas ainda sem validação brasileira: Escalas de Comportamento Adaptativo de Vineland. Os resultados mostraram que esses indivíduos apresentam altas taxas de transtornos mentais ao longo da vida, comportamento adaptativo deficitário e funcionamento global prejudicado. Além disso, observou-se um grande impacto familiar da doença, abandono escolar por falta de condições de acesso e de preparo da própria escola, grande dependência dos indivíduos avaliados e sobrecarga de um único cuidador, geralmente a mãe. Também ficou evidente o peso trazido pelo próprio tratamento, traduzido em uma recusa em aceitar novas propostas clínicas oferecidas. Concluiu-se que a população estudada é altamente vulnerável dos pontos de vista pessoal, familiar e social, sendo necessários mais estudos para seu melhor conhecimento e elaboração de programas e políticas de atendimento mais direcionados para suas necessidades / Mucopolysaccharidoses (MPS) are a group of hereditary metabolic diseases caused by deficient lysossomal enzymes, that lead to progressive physic and/or behavioral abnormalities. A behavioral phenotype is a characteristic pattern of motor, cognitive, linguistic and social observations, consistently associated to a biological condition. That phenotype may be a mental disorder or other behavioral characteristics not necessarily associated to any specific disorder. Referring to MPS, altohugh there are several descriptions of high ocurrence of behavioral problems in patients with Sanfilippo Syndrome (MPS III), the knowledge about behavioral characteristics of the other types of MPS is scarce. This work intended to analyse and describe psychiatric alterations in 22 patients with MPS from three services of medical genetics. Evaluation was made using specific instruments, translated and validated for use with brazilian population: K-SADS-PL, ATA, CARS, CGAS; and one instrument translated but not validated for brazilian population: Vineland Adaptive Behavior Scales. Results showed high lifetime prevalence of mental disorders, deficient adaptive behavior, and poor global functioning. Besides, it was observed intense familiar impact, high drop out rates from school, highly dependent individuals, and excessive burden for the caretaker. It was also evidenced the burden of the treatment itself. The conclusion was that this population is extremely vulnerable, and that it is necessary the realization of more studies for the better understanding of its specific necessitites

As mucopolissacaridoses (MPS) são um grupo de doenças metabólicas hereditárias causadas pela deficiência de enzimas lisossomais específicas, que causam alterações físicas e/ou comportamentais crônicas e progressivas. Um fenótipo comportamental é um padrão característico de observações motoras, cognitivas, linguísticas e sociais consistentemente associado a uma condição biológica. Tal fenótipo pode ser um transtorno mental ou outras características de comportamento não necessariamente associadas a transtornos. No caso específico das mucopolissacaridoses, embora haja diversos relatos na literatura sobre as altas taxas de ocorrência de problemas de comportamento na síndrome de Sanfilippo (MPS III), muito pouco é conhecido sobre as características comportamentais das outras entidades (MPS I, II, IV, VI e VII). Este trabalho pretendeu avaliar e descrever as alterações psiquiátricas encontradas em 22 pacientes com MPS atendidos em três serviços de genética clínica (4 MPS I, 5 MPS II, 1 MPS III, 4 MPS IV, 7 MPS VI, 1 MPS VII). As avaliações foram feitas através de instrumentos específicos, traduzidos e validados para nossa população, a saber: K-SADS PL, ATA, CARS, CGAS; e um instrumento traduzido, mas ainda sem validação brasileira: Escalas de Comportamento Adaptativo de Vineland. Os resultados mostraram que esses indivíduos apresentam altas taxas de transtornos mentais ao longo da vida, comportamento adaptativo deficitário e funcionamento global prejudicado. Além disso, observou-se um grande impacto familiar da doença, abandono escolar por falta de condições de acesso e de preparo da própria escola, grande dependência dos indivíduos avaliados e sobrecarga de um único cuidador, geralmente a mãe. Também ficou evidente o peso trazido pelo próprio tratamento, traduzido em uma recusa em aceitar novas propostas clínicas oferecidas. Concluiu-se que a população estudada é altamente vulnerável dos pontos de vista pessoal, familiar e social, sendo necessários mais estudos para seu melhor conhecimento e elaboração de programas e políticas de atendimento mais direcionados para suas necessidades / Mucopolysaccharidoses (MPS) are a group of hereditary metabolic diseases caused by deficient lysossomal enzymes, that lead to progressive physic and/or behavioral abnormalities. A behavioral phenotype is a characteristic pattern of motor, cognitive, linguistic and social observations, consistently associated to a biological condition. That phenotype may be a mental disorder or other behavioral characteristics not necessarily associated to any specific disorder. Referring to MPS, altohugh there are several descriptions of high ocurrence of behavioral problems in patients with Sanfilippo Syndrome (MPS III), the knowledge about behavioral characteristics of the other types of MPS is scarce. This work intended to analyse and describe psychiatric alterations in 22 patients with MPS from three services of medical genetics. Evaluation was made using specific instruments, translated and validated for use with brazilian population: K-SADS-PL, ATA, CARS, CGAS; and one instrument translated but not validated for brazilian population: Vineland Adaptive Behavior Scales. Results showed high lifetime prevalence of mental disorders, deficient adaptive behavior, and poor global functioning. Besides, it was observed intense familiar impact, high drop out rates from school, highly dependent individuals, and excessive burden for the caretaker. It was also evidenced the burden of the treatment itself. The conclusion was that this population is extremely vulnerable, and that it is necessary the realization of more studies for the better understanding of its specific necessitites

L’objectif général de cette thèse de doctorat est de mieux comprendre comment le public interprète les nouvelles scientifiques portant sur la génétique humaine, plus précisément les nouvelles portant sur la génétique des comportements et celles portant sur la génétique des groupes raciaux. L’ouvrage prend la forme d’une thèse par article. Le Chapitre 1 introduit le lecteur aux buts et aux pratiques de la vulgarisation scientifique, présente un sommaire de la recherche sur les effets des médias, résume les principaux travaux produits par le champ de la génopolitique, et définit la structure des croyances du public à l’égard de l’influence de la génétique sur les traits humains. Le Chapitre 2 présente les fondements de la méthode expérimentale, il en explique les atouts et il offre des exemples de différents types de devis expérimentaux utilisés en science politique. Toutes les recherches produites dans cette thèse reposent au moins en partie sur cette méthode. Le Chapitre 3 présente les résultats d’une expérience de sondage qui vise à mesurer l’effet de la lecture d’une nouvelle à propos de la recherche en génétique des comportements sur des participants. L’étude démontre que le public interprète la nouvelle avec maladresse et tend à généraliser l’influence de la génétique à d’autres traits humains qui n’y sont pas mentionnés. J’avance l’hypothèse qu’un raccourci psychologique amplement documenté puisse expliquer cette réaction : l’heuristique de l’ancrage et de l’ajustement. Le Chapitre 4 présente lui aussi les résultats d’une expérience de sondage. L’étude consiste à manipuler certaines informations du contenu d’une nouvelle sur la génopolitique de manière à vérifier si certains éléments sont particulièrement susceptibles de mener à la généralisation hâtive mise en évidence dans le Chapitre 3. Les analyses suggèrent que cette généralisation est amplifiée lorsque la nouvelle présente de hauts niveaux d’héritabilité tirés d’études de jumeaux, ainsi que lorsqu’elle présente des travaux de génétique des populations visant à étudier l’origine des différences géographiques. Ce chapitre présente des recommandations à l’égard des journalistes scientifiques. Le Chapitre 5 s’intéresse à un aspect différent de la génétique humaine : celui de la génétique des races. L’objectif de cette recherche est de comprendre comment le public réagit aux travaux qui invalident l’idée selon laquelle les humains sont divisés en différentes races génétiquement distinctes. Les analyses de données transversales ainsi que les résultats d’une expérience de sondage convergent et indiquent que les conservateurs et les libéraux réagissent de manière diamétralement opposée à cette information. D’un côté, les libéraux acceptent le constat scientifique et réduisent leur impression que la génétique explique en partie les inégalités sociales; de l’autre, les conservateurs rejettent l’argument avec une intensité si forte que le rôle qu’ils attribuent aux différences génétiques s’en voit bonifié. Ces résultats sont interprétés à partir de la théorie du raisonnement motivé. Enfin, le Chapitre 6 résume les principaux constats, met en évidence les contributions que ma thèse apporte à la science politique et à la communication scientifique, et présente quelques pistes pour la recherche future. / The main objective of this doctoral thesis is to improve our understanding of how the public interprets scientific news about human genetics, specifically, behavioral genetics and the genetic underpinnings of racial groups. The core of the dissertation is a collection of three research articles and one book chapter. Chapter 1 introduces the readers to the goals and practices of science journalism, presents a summary of the literature on media effects, summarizes research on genopolitics, and discusses findings in public opinion on how people understand genetic influence on human characteristics. Chapter 2 presents the rationale behind the experimental method, explains its pros and cons, and provides examples of how different types of research designs have been used in political science. All the empirical evidence presented in this dissertation rests at least in part on experiments. Chapter 3 presents the results of a survey experiment that aims to measure the effects on individuals of reading a news article about behavioral genetics research. The study suggests that the public has difficulty in making sense of such research findings. The results show that participants tend to generalize the conclusions of one particular genetic study to other characteristics not mentioned by the study. I hypothesize that these results can be explained by a well-known and widely documented psychological process: the use of anchoring and adjustment heuristics. Chapter 4 presents the results of a second survey experiment. This experiment manipulates the content of a news article about behavioral genetics. The purpose of the manipulation is to test whether particular aspects of article’s message are more likely than others to cause the hasty generalizations revealed in Chapter 3. The findings show that the tendency to generalization is greater when the news presents high heritability estimates derived from twin studies or insights from research using population genetics methods to account for aggregate geographic difference. Based on these findings, the chapter develops recommendations for science journalists interested in covering behavioral genetics. Chapter 5 focuses on a different field of human genetic research, namely, that investigating the genetic bases of racial differences. The chapter’s aim is to improve our understanding of how the public reacts when exposed to scientific claims arguing against the idea that that human beings belong to different, genetically distinct races. Both cross sectional survey data and experimental data suggest that conservatives and liberals react to this information in opposing ways. Liberals tend to accept such arguments and temper their beliefs that genetic differences account for racial inequalities. By contrast, conservatives reject the arguments so strongly that exposure to them actually strengthens these citizens’ beliefs that genetics explain a proportion of racial inequality. These results are interpreted from the perspective of motivated reasoning theory. Finally, Chapter 6 summarizes the main findings of the doctoral dissertation, highlights its contribution to the discipline of political science and the field of science communication, and suggests directions for future research.

Much recent scholarship in Victorian studies has viewed sexuality as historically contingent and constructed primarily within the realm of discourse or social organization. In contrast, the following study details species-typical and universal aspects of human sexuality that must be adequately theorized if an accurate model of the ideological forces impacting Victorian sexuality is to be fashioned. After a short survey of previous scholarly projects that examine literature through the lens of biology—much of it marred by an obvious antipathy toward all attempts to discover the involvement of ideology in human behavior—this study presents a lengthy primer to the modern study of evolutionary psychology, behavioral genetics, and human sexuality. Because the use of science is still relatively rare in literary studies, the first chapters are designed both to convince the reader of the necessity of considering biology and evolution in examining human sexuality, as well as to provide the general educated scholar in our field with the basic framework of knowledge necessary to follow the remainder of the text. Chapter three follows with a detailed examination of the sources of the political resistance to biological and genetic models of human behavior within liberal arts and social science departments, and chapter four presents an evolutionary and biochemical model for the apprehension of art that locates the origins of culture within the evolutionarily-fashioned brains of individuals and attempts to recuperate the concept of aesthetic emotion and foreground the special nature of erotica in its ability to produce immediate neurochemical effects in the brains of its consumers. Finally, the study examines works of Victorian literature, especially My Secret Life, to demonstrate the deficiencies in constructionist and interactionist theories of human sexuality while detailing the new readings that emerge when one is aware of the biological basis of human mate selection mechanisms.