| 1. |
- Shungin, Dmitry, et al.
(author)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Journal article (peer-reviewed)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 2. |
- Forssén, Jens, 1968, et al.
(author)
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Auralization model for the perceptual evaluation of tyre–road noise
- 2018
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In: Applied Acoustics. - : Elsevier BV. - 0003-682X .- 1872-910X. ; 132, s. 232-242
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Journal article (peer-reviewed)abstract
- Due to improvements in combustion-engines and use of electric-engines for cars, tyre noise has become the prominent noise source also at lower speeds. Models exist that simulate the noise produced by a rolling tyre, as do models that auralize different traffic situations from basic data. In this paper, a novel auralization method is introduced, with the purpose to enable synthesis of useful car pass-by sound signals for various situations. The method is based on an established model for tyre noise levels (SPERoN) that is combined with a validated auralization tool (LISTEN). In the LISTEN approach, source signals for tyre–road interaction and propulsion are produced from data based on recorded pass-by sounds. In the combined model, the tyre–road interaction data is shaped by the spectra estimated in SPERoN and synthesized back into a pass-by signal. The combined model is made to agree spectrally with measurements for a receiver at 7.5 m distance. Psychoacoustic judgments were used to compare the modelled signals with recorded signals, and the pass-by sounds for a given listener position showed promising quality and accuracy with respect to perceived pleasantness.
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| 3. |
- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 4. |
- Hoffmann, Alice, 1983, et al.
(author)
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Auralization of simulated tyre noise: Psychoacoustic validation of a combined model
- 2019
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In: Applied Acoustics. - : Elsevier BV. - 0003-682X .- 1872-910X. ; 145, s. 220-227
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Journal article (peer-reviewed)abstract
- Due to improvements on combustion-engines and electric-engines for cars, tyre noise has become the prominent noise source at low and medium speeds. Models exist that simulate the noise produced by a rolling tyre, as do models that auralize different traffic situations from a basic data set. In this paper, an established model for tyre noise (SPERoN) is combined with an auralization tool. The combined model can predict the spectrum of the sound at 7.5 m, as well as reproduce the sound for a given listener position. The auralization uses a methodology where recorded sounds are converted to source signals for engine and tyre/road-interaction. These can be shaped by the spectra estimated in SPERoN and synthesized back into a pass-by signal. Psychoacoustic judgements were used to compare the modelled signals with recorded signals. To see how well the modelled signals match the real recorded signals for perception, two listening-tests were performed. The simulated and recorded signals were rated by pleasantness, loudness, roughness and sharpness using semantic differentials. It was found that responses for simulated and recorded signals correlate for all cases, but rankings could not be reproduced exactly. The model can be further improved to be more applicable for listening tests.
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| 5. |
- Hoffmann, Alice, 1983, et al.
(author)
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Perception of Tyre Noise: Can Tyre Noise be Differentiated and Characterized by the Perception of a Listener Outside the Car?
- 2016
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In: Acta Acustica united with Acustica. - : Wissenschaftliche Verlagsgesellschaft mbH. - 1610-1928 .- 1861-9959. ; 102:6, s. 992-998
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Journal article (peer-reviewed)abstract
- When constructing a tyre, it is of importance that improvements and planned changes are not only physically measurable, but that they also can be perceived by a listener. Tyre/road noise becomes a more important focus area, especially with the growing market of electric vehicles. In the design of tyre/road sound, there are three main aims: to reduce the overall sound level, to increase pleasantness and to do so still maintaining the carried information about e.g. driving conditions. To be able to do this, an understanding of how physical changes in a tyre are reflected in the perception of the same tyre is essential. In the present study, the aim is thus to determine if the rolling noise of a tyre can be both differentiated and characterized by its perceptual qualities. The focus is on the perception of the sound outside the car, perceived by, for example, a pedestrian. Listeners have judged different road tyre combinations and their perception in terms of their emotional responses (pleasantness, activation and stress) and their psychoacoustic responses (loudnes s, sharpness, roughness, and pitch). The results confirmed that rolling noise can be perceptually differentiated. Further, it is possible to differentiate between the effects of the street and the effects of the tyre on all emotional and most psychoacoustic parameters. The results suggest that changes to both road surfaces and tyres can affect both emotional and psychoacoustic perceptual qualities.
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| 6. |
- Hoffmann, Alice, 1983, et al.
(author)
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There’s a car coming? - Psychometric function for car pass-by in background noise based on simulated data
- 2015
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In: Euronoise 2015, 10th European Congress on Noise Control Engineering. - 2226-5147. ; , s. 2417-2421
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Conference paper (peer-reviewed)abstract
- To detect an approaching car in background noise is an important aspect of traffic safety. Therefore itis essential to understand the determinants that makes people recognize an approaching car especiallywhen the cars become very quiet at low speeds as it is the case for electrical cars for instance. Moststudies on the detection of passenger cars in background noise are based on recorded signals. Thisrequires that suitable recordings are available both for the background sound as well as the test sound(i.e. the sound of the approaching vehicle). Due to the limited control of such situations the degreesof freedom to be varied in such experiments is limited as well. In the presented study a differentapproach has been employed. The utilized sounds are based on an auralization method that allowsfor simulating vehicle sounds including both tyre/road noise and propulsion noise. Single car eventscan thus be superposed to background sound with full control of all relevant parameters. The usedauralization method has in earlier studies been validated for giving good perceptual ratings comparedto recorded sounds. The method allows for evaluating the psychometric functions for single parametersand hopefully give a deeper understanding of the perceptual space for a car in background noise. Inthe present study the reaction time is measured for the detection of a car (test vehicle) passing byin the presence of background noise from a road with high traffic flow. The distance between the thepath of the test vehicle and the highly trafficked road is varied. All other parameters (i.e. car-type,road surface, speed, etc.) are kept constant. The study shows that there is a logarithmic relationbetween the response times and the distance between the the track of the test car and the road withhigh traffic volume. At the same time there is a linear relation between reaction time and signal tonoise ratio (i.e. the equivalent sound pressure level in relation to the background level).
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| 7. |
- Hou, Liping, et al.
(author)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 8. |
- Satizabal, Claudia L., et al.
(author)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Journal article (peer-reviewed)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 9. |
- Smith, Jennifer A, et al.
(author)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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In: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Journal article (peer-reviewed)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 10. |
- Stitziel, Nathan O., et al.
(author)
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Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease
- 2016
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144
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Journal article (peer-reviewed)abstract
- BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
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