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The Genetics of Cognition
Uncovering the genetic underpinnings of cognition
Trevor W. Robbins and Stavroula Kousta
Trends in Cognitive Sciences | Special Issue: The Genetics of Cognition
Volume 15, Issue 9, September 2011, Pages 375-377
Excerpt:
No one today can ignore the genetic approach to cognition and behavior, given the huge achievements of the Human Genome Project. The initial impact of studies of individual differences in genetic polymorphisms,such as the catechol-O-methyl transferase (COMT) gene, and their relationship to such core cognitive concepts asworking memory (in this case via its modulation by pre-frontal dopamine [1]) has been immense, catching theimagination of many cognitive neuroscientists. Here is a way, for example, to evaluate the effect of individual differences in neurotransmitter function without the need to administer drugs. Alternatively, possible heterogeneity in behavioral performance or patterns of neural networkactivation revealed through functional neuroimaging, maybe resolved by taking into account genetic factors. Taken together, the contributions in this special issue address the genetic underpinnings of key aspects of cognition, such as memory, intelligence, reward processing, as well as emotion and personality, in the context of both healthy populations and in key disorders, such as schizophrenia, autism, and addiction. Collectively, the articles discuss evidence from a variety of perspectives and differentapproaches, including twin, linkage, candidate gene, genome-wide association, imaging genetics, gene x environ-environment interaction, and gene expression studies, providing insight into the strengths and challenges for each approach.
A key insight arising from several articles in this issue is that variations in complex psychological attributes such as intelligence and psychosis are usually likely to be determined by multiple genes, each exerting a small effect. Moreover, it is becoming increasingly clear that, so as to establish valid behavioral–genetic correlations, it is necessary to test large populations, in order to avoid spurious false positive effects arising from the very large number of contributing genes. Finally, the well-known mantra of the importance of ‘gene x environment interaction’ has gained additional complexity from the discovery of effects of imprinted genes and epigenetic factors. As several articles in this special issue make clear, some of the inspiration for the genetic (and epigenetic) approach to cognition comes from our need to understand better the origin of disorders in mental health. The hope is that by understanding their genetic basis, we will be able to identify the causal molecular pathology of different disorders and capitalize on proteomic approaches for treatments. By paying attention to possible intermediate phenotypes(‘endophenotypes’), which may have a biochemical, neuralor even cognitive-behavioral basis, we may be able to bridge the present daunting gap between genes and psychopathology.
Rapid advances in the field of genetics have also raised several ethical and legal questions. In the first article in this issue, Morse discusses one such question: what are the implications of genetic research for the concept of criminal responsibility? Morse explains that the concept of criminal responsibility as determined by law is based on identifying relevant mental states: was there an intention to commit a crime? And did the individual possess knowledge of wrong-doing? Genetic research, on the other hand, is concerned with mechanistic causation, and causation does not currently constitute an excusing condition in law. Unless it can be shown that biological causation is directly responsible for aparticular mental state, it cannot be used either as a mitigating factor or an excuse for a criminal act. But one could argue, and some have, that an individual’s genetic make-up completely determines behaviour, hence suggesting that the concept of criminal responsibility as defined by law shouldbe completely revised: it is biology, not mental states thatmatter. However, Morse argues, genetic research (or any other research) has provided no evidence to support the idea that mental states are redundant and do not have a causal role in driving behavior. And denying a critical role formental states would do away with human motivation to do anything whatsoever, not just a criminal act.
The four review articles that follow address different aspects of cognitive and emotional processes from a genetic perspective.
....
Munafo and Flint critically review the personality genetics literature, as a case study of the missing heritability problem: as with any other complex trait, the genetic architecture of personality traits, the authors argue, is likely to be the result of several hundreds, if not thousands, of small effect loci, which together none the less produce substantial heritability. Early candidate gene studies found positive associations of the serotonin trans-porter gene (SLC6A4) with measures of neuroticism, and the dopamine D4 receptor gene (DRD4) with noveltyseeking. Although follow up candidate gene studies, aswell as gene by environment interaction studies, abound,meta-analytic studies suggest that these genes, as well asother candidate genes identified, have a very small effect at best. In fact, a number of recent genome-wide association studies have failed to identify any locus with clear genome-wide significance. Munafo and Flint argue that, in order to achieve progress in this field, it is important to consider issues of power, statistical stringency and independent replication; and to acknowledge that, as with other complex traits, such as blood pressure and height, variation in personality is the outcome of the combined effect of several small effect loci.
In a related contribution, Bevilacqua and Goldmandiscuss the genetic basis of emotional processing, personality and temperament, focusing on functional variants at five genes: COMT, SLC6A4, neuropeptide Y (NPY), a glucocorticoid receptor-regulating cochaperone of stressproteins (FKBP5) and pituitary adenylate cyclase-activating polypeptide (PACAP), as illustrative of the effects of genes on emotion. They address factors that alter or confound the effects of these genes, especially gene x environ-environment interactions, as emotionality is strongly influenced by exposure to stress. They acknowledge the issues highlighted in Munafo and Flint’s contribution—the few genome-wide association studies that have examined the effects on emotion of genes identified in candidate genestudies have indeed failed to yield any significant resultsfor these genes. And they converge with Munafo and Flint on likely explanations (statistical power and the fact that emotionality is likely to be underpinned by several different loci of small effect). However, despite lack of genome-wide significance in the few studies carried out up to now, the authors argue, these genes have large effects on metabolic responses of the brain to emotional stimuli assessed in real time by brain imaging, hence validating the effectsof these genes in emotion.
link to database http://www.sciencedirect.com/science/article/pii/S1364661311001483
Uncovering the genetic underpinnings of cognition
Trevor W. Robbins and Stavroula Kousta
Trends in Cognitive Sciences | Special Issue: The Genetics of Cognition
Volume 15, Issue 9, September 2011, Pages 375-377
Excerpt:
No one today can ignore the genetic approach to cognition and behavior, given the huge achievements of the Human Genome Project. The initial impact of studies of individual differences in genetic polymorphisms,such as the catechol-O-methyl transferase (COMT) gene, and their relationship to such core cognitive concepts asworking memory (in this case via its modulation by pre-frontal dopamine [1]) has been immense, catching theimagination of many cognitive neuroscientists. Here is a way, for example, to evaluate the effect of individual differences in neurotransmitter function without the need to administer drugs. Alternatively, possible heterogeneity in behavioral performance or patterns of neural networkactivation revealed through functional neuroimaging, maybe resolved by taking into account genetic factors. Taken together, the contributions in this special issue address the genetic underpinnings of key aspects of cognition, such as memory, intelligence, reward processing, as well as emotion and personality, in the context of both healthy populations and in key disorders, such as schizophrenia, autism, and addiction. Collectively, the articles discuss evidence from a variety of perspectives and differentapproaches, including twin, linkage, candidate gene, genome-wide association, imaging genetics, gene x environ-environment interaction, and gene expression studies, providing insight into the strengths and challenges for each approach.
A key insight arising from several articles in this issue is that variations in complex psychological attributes such as intelligence and psychosis are usually likely to be determined by multiple genes, each exerting a small effect. Moreover, it is becoming increasingly clear that, so as to establish valid behavioral–genetic correlations, it is necessary to test large populations, in order to avoid spurious false positive effects arising from the very large number of contributing genes. Finally, the well-known mantra of the importance of ‘gene x environment interaction’ has gained additional complexity from the discovery of effects of imprinted genes and epigenetic factors. As several articles in this special issue make clear, some of the inspiration for the genetic (and epigenetic) approach to cognition comes from our need to understand better the origin of disorders in mental health. The hope is that by understanding their genetic basis, we will be able to identify the causal molecular pathology of different disorders and capitalize on proteomic approaches for treatments. By paying attention to possible intermediate phenotypes(‘endophenotypes’), which may have a biochemical, neuralor even cognitive-behavioral basis, we may be able to bridge the present daunting gap between genes and psychopathology.
Rapid advances in the field of genetics have also raised several ethical and legal questions. In the first article in this issue, Morse discusses one such question: what are the implications of genetic research for the concept of criminal responsibility? Morse explains that the concept of criminal responsibility as determined by law is based on identifying relevant mental states: was there an intention to commit a crime? And did the individual possess knowledge of wrong-doing? Genetic research, on the other hand, is concerned with mechanistic causation, and causation does not currently constitute an excusing condition in law. Unless it can be shown that biological causation is directly responsible for aparticular mental state, it cannot be used either as a mitigating factor or an excuse for a criminal act. But one could argue, and some have, that an individual’s genetic make-up completely determines behaviour, hence suggesting that the concept of criminal responsibility as defined by law shouldbe completely revised: it is biology, not mental states thatmatter. However, Morse argues, genetic research (or any other research) has provided no evidence to support the idea that mental states are redundant and do not have a causal role in driving behavior. And denying a critical role formental states would do away with human motivation to do anything whatsoever, not just a criminal act.
The four review articles that follow address different aspects of cognitive and emotional processes from a genetic perspective.
....
Munafo and Flint critically review the personality genetics literature, as a case study of the missing heritability problem: as with any other complex trait, the genetic architecture of personality traits, the authors argue, is likely to be the result of several hundreds, if not thousands, of small effect loci, which together none the less produce substantial heritability. Early candidate gene studies found positive associations of the serotonin trans-porter gene (SLC6A4) with measures of neuroticism, and the dopamine D4 receptor gene (DRD4) with noveltyseeking. Although follow up candidate gene studies, aswell as gene by environment interaction studies, abound,meta-analytic studies suggest that these genes, as well asother candidate genes identified, have a very small effect at best. In fact, a number of recent genome-wide association studies have failed to identify any locus with clear genome-wide significance. Munafo and Flint argue that, in order to achieve progress in this field, it is important to consider issues of power, statistical stringency and independent replication; and to acknowledge that, as with other complex traits, such as blood pressure and height, variation in personality is the outcome of the combined effect of several small effect loci.
In a related contribution, Bevilacqua and Goldmandiscuss the genetic basis of emotional processing, personality and temperament, focusing on functional variants at five genes: COMT, SLC6A4, neuropeptide Y (NPY), a glucocorticoid receptor-regulating cochaperone of stressproteins (FKBP5) and pituitary adenylate cyclase-activating polypeptide (PACAP), as illustrative of the effects of genes on emotion. They address factors that alter or confound the effects of these genes, especially gene x environ-environment interactions, as emotionality is strongly influenced by exposure to stress. They acknowledge the issues highlighted in Munafo and Flint’s contribution—the few genome-wide association studies that have examined the effects on emotion of genes identified in candidate genestudies have indeed failed to yield any significant resultsfor these genes. And they converge with Munafo and Flint on likely explanations (statistical power and the fact that emotionality is likely to be underpinned by several different loci of small effect). However, despite lack of genome-wide significance in the few studies carried out up to now, the authors argue, these genes have large effects on metabolic responses of the brain to emotional stimuli assessed in real time by brain imaging, hence validating the effectsof these genes in emotion.
link to database http://www.sciencedirect.com/science/article/pii/S1364661311001483
