1. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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2. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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3. |
- León-Domínguez, Umberto, et al.
(författare)
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A Frontal Neuropsychological Profile in Fitness to Drive
- 2020
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Ingår i: Accident Analysis and Prevention. - : Elsevier Ltd. - 0001-4575 .- 1879-2057. ; 148
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Tidskriftsartikel (refereegranskat)abstract
- Traffic accidents are a global concern due to the elevated mortality rates of both drivers and pedestrians. The World Health Organization declared 2011-2020 as the Decade of Action for Road Safety, endorsing initiatives to reduce traffic-related deaths. Yet, despite these incentives, fatal accidents still occur. Different studies have linked deficits in executive functions to risky driving attitudes and crashes. The present study focuses on demographic, cognitive and personality factors, related to the prefrontal cortex, that are characteristic of drivers prone to risky behavior behind the wheel. The penalty Points System was used to classify drivers as “safe”, with no point loss over a two-year period, or “risky”, with full point loss during the same interval. A neuropsychological assessment of prefrontal cognitive functions was carried out on each group to identify variables associated with safe and risky behavior. Neuropsychological indexes were obtained from a continuous performance task without cue (Simple Attention), a continuous performance task with cue (Conditioned Attention), the Tower of Hanoi test and the Neurologically-related Changes in Personality Inventory (NECHAPI). A Discriminant Analysis (DA) found that education level, reaction times in Simple and Conditioned Attention, learning errors in the Tower of Hanoi and vulnerability in the personality test, best predicted whether drivers were likely to be in the safe or risky group. Finally, a cross-validation analysis performed on the same sample correctly classified 87.5% of the drivers. These data suggest that prefrontal dysfunction contributes to risky behavior behind the wheel. The inclusion of cognitive programs to identify and train drivers with this propensity could reduce risky driving, and consequently, save lives on the road.
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4. |
- León-Domínguez, Umberto, et al.
(författare)
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Safe Driving and Executive Functions in Healthy Middle-Aged Drivers
- 2017
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Ingår i: Applied neuropsychology. Adult. - : Routledge. - 2327-9095 .- 2327-9109. ; 24:5, s. 395-403
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of the point system driver’s license in several European countries could offer a valid framework for evaluating driving skills. This is the first study to use this framework to assess the functional integrity of executive functions in middle-aged drivers with full points, partial points or no points on their driver’s license (N = 270). The purpose of this study is to find differences in executive functions that could be determinants in safe driving. Cognitive tests were used to assess attention processes, processing speed, planning, cognitive flexibility, and inhibitory control. Analyses for covariance (ANCOVAS) were used for group comparisons while adjusting for education level. The Bonferroni method was used for correcting for multiple comparisons. Overall, drivers with the full points on their license showed better scores than the other two groups. In particular, significant differences were found in reaction times on Simple and Conditioned Attention tasks (both p-values < 0.001) and in number of type-III errors on the Tower of Hanoi task (p = 0.026). Differences in reaction time on attention tasks could serve as neuropsychological markers for safe driving. Further analysis should be conducted in order to determine the behavioral impact of impaired executive functioning on driving ability.
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