Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Current and emerging developments in subseasonal to decadal prediction

Weather and climate variations of subseasonal to decadal timescales can have enormous social, economic and environmental impacts, making skillful predictions on these timescales a valuable tool for decision makers. As such, there is a growing interest in the scientific, operational and applications communities in developing forecasts to improve our foreknowledge of extreme events. On subseasonal to seasonal (S2S) timescales, these include high-impact meteorological events such as tropical cyclones, extratropical storms, floods, droughts, and heat and cold waves. On seasonal to decadal (S2D) timescales, while the focus remains broadly similar (e.g., on precipitation, surface and upper ocean temperatures and their effects on the probabilities of high-impact meteorological events), understanding the roles of internal and externally-forced variability such as anthropogenic warming in forecasts also becomes important. The S2S and S2D communities share common scientific and technical challenges. These include forecast initialization and ensemble generation; initialization shock and drift; understanding the onset of model systematic errors; bias correct, calibration and forecast quality assessment; model resolution; atmosphere-ocean coupling; sources and expectations for predictability; and linking research, operational forecasting, and end user needs. In September 2018 a coordinated pair of international conferences, framed by the above challenges, was organized jointly by the World Climate Research Programme (WCRP) and the World Weather Research Prograame (WWRP). These conferences surveyed the state of S2S and S2D prediction, ongoing research, and future needs, providing an ideal basis for synthesizing current and emerging developments in these areas that promise to enhance future operational services. This article provides such a synthesis

The Role of Emotion in the Interpretation of Sounds

Historically there has been a conceptual distinction between reason and passion, i.e. emotions and higher levels of cognitive processing has been viewed apart from each other and studied separately. Recent research suggest a more dynamic interaction where the emotional responses may affect several aspects of higher level cognitive functioning. This thesis focuses on how an integrated analysis can discern the relationship between interpretation and emotion responses in auditory signals. It concludes that the interpretations of perceptual qualities in sounds are affected by the emotional responses to the sounds. Paper I studied auditory alerts in two stages. First by a general dissimilarity rating where the participants rated perceived dissimilarity. This resulted in a two-dimensional multidimensional scaling solution. In a second experiment the participants rated each sound with semantic descriptors as well as their emotional reactions measured by hedonic valence and arousal. The results from the two experiments were then integrated by the use of multidimensional perceptual unfolding and a set mediation analyses. The latter showed that part of the cognitive categorization of the semantic descriptors was mediated by the emotional reactions to the sounds. Paper II further investigated the role of emotion in interpretation of perceptual qualities in everyday sounds. The participants conducted a general dissimilarity rating of 12 sounds, parametrically chosen from three levels of hedonic valence (high, neutral, low) and four categories of sounds (human, animals, environmental, and mechanical). Afterwards the participants rated their emotional reaction to each sound. At a second occasion, same participants conducted seven focused dissimilarity ratings concerning emotional aspects and perceptual qualities in the sounds. The general dissimilarity ratings resulted in a three-dimensional scaling. Both the emotional reactions as well as the perceptual qualities from the specific dissimilarity ratings (in at least one dimension) could explain the first dimension in the general perceptual space. Subsequent mediation analyses revealed that the emotional responses mediated the physical perception. The second and the third dimension were explained by theory-categorization. E.g. in the second dimension the participants differentiated between living and nonliving sources. The two paper together support the use of integrated analysis to determine the underlying perceptual mechanisms in perception of sounds. The research suggests that emotional reactions are fundamental in interpretation of perceptual qualities in sounds and that emotion categorization is a strong influence in perception. This further suggests that auditory signals are promising in promoting emotion regulation. This could be applied in e.g. restorative soundscapes

The Role of Emotion in the Interpretation of Sounds

Historically there has been a conceptual distinction between reason and passion, i.e. emotions and higher levels of cognitive processing has been viewed apart from each other and studied separately. Recent research suggest a more dynamic interaction where the emotional responses may affect several aspects of higher level cognitive functioning. This thesis focuses on how an integrated analysis can discern the relationship between interpretation and emotion responses in auditory signals. It concludes that the interpretations of perceptual qualities in sounds are affected by the emotional responses to the sounds.Paper I studied auditory alerts in two stages. First by a general dissimilarity rating where the participants rated perceived dissimilarity. This resulted in a two-dimensional multidimensional scaling solution. In a second experiment the participants rated each sound with semantic descriptors as well as their emotional reactions measured by hedonic valence and arousal. The results from the two experiments were then integrated by the use of multidimensional perceptual unfolding and a set mediation analyses. The latter showed that part of the cognitive categorization of the semantic descriptors was mediated by the emotional reactions to the sounds. Paper II further investigated the role of emotion in interpretation of perceptual qualities in everyday sounds. The participants conducted a general dissimilarity rating of 12 sounds, parametrically chosen from three levels of hedonic valence (high, neutral, low) and four categories of sounds (human, animals, environmental, and mechanical). Afterwards the participants rated their emotional reaction to each sound. At a second occasion, same participants conducted seven focused dissimilarity ratings concerning emotional aspects and perceptual qualities in the sounds. The general dissimilarity ratings resulted in a three-dimensional scaling. Both the emotional reactions as well as the perceptual qualities from the specific dissimilarity ratings (in at least one dimension) could explain the first dimension in the general perceptual space. Subsequent mediation analyses revealed that the emotional responses mediated the physical perception.The second and the third dimension were explained by theory-categorization. E.g. in the second dimension the participants differentiated between living and nonliving sources. The two paper together support the use of integrated analysis to determine the underlying perceptual mechanisms in perception of sounds. The research suggests that emotional reactions are fundamental in interpretation of perceptual qualities in sounds and that emotion categorization is a strong influence in perception. This further suggests that auditory signals are promising in promoting emotion regulation. This could be applied in e.g. restorative soundscapes

The role of embodied emotions in perceptual decisions and categorization of sounds

How do people react emotionally to sound? In particular how does emotion affect interpretation, perceptual judgment and categorization of auditory stimuli? This thesis explored 1) how sound and emotion relate to each other, 2) whether this relationship can be modified by embodied associations and 3) if the emotional responses influence the perceptual decisions of sounds. Paper I investigated the emotional reactions to the perception of the acoustic properties of frequency and intensity. Paper II investigated whether the relationship between emotion and perception could be associated with each other through an embodied perspective. Paper III further investigated the embodied relations, using thermal stimuli instead, to discern whether embodied associations would influence information processing. Paper IV and Paper V examined whether emotional responses influence the perceptual decisions of sound, and whether additional non-physical factors in the sound affect this relationship.Taken together, in each of the empirical studies we may conclude that emotions are central for perception and perceptual decisions of sounds. Further, this relationship must take the embodied perspective into account. The co-experiences of emotional responses and perceptual aspects appear to create a robust association pattern that affects both inter-personal relations as well as intra-personal reactions. It may also be concluded that there are several application possibilities in the intersection between emotion, perception and cognition, both concerning general health and well-being as well as in sound design of various products