| 1. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 2. |
- Synofzik, M., et al.
(författare)
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Mutant superoxide dismutase-1 indistinguishable from wild-type causes ALS
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP): Policy B - Oxford Open Option B. - 0964-6906 .- 1460-2083. ; 21:16, s. 3568-3574
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Tidskriftsartikel (refereegranskat)abstract
- A reason for screening amyotrophic lateral sclerosis (ALS) patients for mutations in the superoxide dismutase-1 (SOD1) gene is the opportunity to find novel mutations with properties that can give information on pathogenesis. A novel c.352Cgreater thanG (L117V) SOD1 mutation was found in two Syrian ALS families living in Europe. The disease showed unusually low penetrance and slow progression. In erythrocytes, the total SOD1 activity, as well as specific activity of the mutant protein, was equal in carriers of the mutation and family controls lacking SOD1 mutations. The structural stabilities of the L117V mutant and wild-type SOD1 under denaturing conditions were likewise equal, but considerably lower than that of murine SOD1. As analyzed with an ELISA specific for misfolded SOD1 species, no differences were found in the content of misfolded SOD1 protein between extracts of fibroblasts from wild-type controls and from an L117V patient. In contrast, elevated levels of misfolded SOD1 protein were found in fibroblasts from ALS patients carrying seven other mutations in the SOD1 gene. We conclude that mutations in SOD1 that result in a fully stable protein are associated with low disease penetrance for ALS and may be found in cases of apparently sporadic ALS. Wild-type human SOD1 is moderately stable, and was found here to be within the stability range of ALS-causing SOD1 variants, lending support to the hypothesis that wild-type SOD1 could be more generally involved in ALS pathogenesis.
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| 3. |
- McKay, James D., et al.
(författare)
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A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- 2011
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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| 4. |
- Ossewaarde, Lindsey, et al.
(författare)
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Changes in functioning of mesolimbic incentive processing circuits during the premenstrual phase
- 2010
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Ingår i: Social cognitive and affective neuroscience. - : Oxford University Press (OUP). - 1749-5024 .- 1749-5016.
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Tidskriftsartikel (refereegranskat)abstract
- The premenstrual phase of the menstrual cycle is associated with marked changes in normal and abnormal motivated behaviors. Animal studies suggest that such effects may result from actions of gonadal hormones on the mesolimbic dopamine (DA) system. We therefore investigated premenstrual changes in reward-related neural activity in terminal regions of the DA system in humans. Twenty-eight healthy young women underwent functional magnetic resonance imaging on 2 days during the menstrual cycle, once during the late follicular phase and once during the premenstrual phase, in counterbalanced order. Using a modified version of the monetary incentive delay task, we assessed responsiveness of the ventral striatum to reward anticipation. Our results show enhanced ventral striatal responses during the premenstrual as compared to the follicular phase. Moreover, this effect was most pronounced in women reporting more premenstrual symptoms. These findings provide support for the notion that changes in functioning of mesolimbic incentive processing circuits may underlie premenstrual changes in motivated behaviors. Notably, increases in reward-cue responsiveness have previously been associated with DA withdrawal states. Our findings therefore suggest that the sharp decline of gonadal hormone levels in the premenstrual phase may trigger a similar withdrawal-like state.
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| 5. |
- Ossewaarde, Lindsey, et al.
(författare)
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Neural mechanisms underlying changes in stress-sensitivity across the menstrual cycle
- 2010
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 35:1, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- Hormonal fluctuations across the menstrual cycle are thought to play a central role in premenstrual mood symptoms. In agreement, fluctuations in gonadal hormone levels affect brain processes in regions involved in emotion regulation. Recent findings, however, implicate psychological stress as a potential mediating factor and thus, we investigated whether effects of moderate psychological stress on relevant brain regions interact with menstrual cycle phase. Twenty-eight healthy women were tested in a crossover design with menstrual cycle phase (late luteal versus late follicular) and stress (stress induction versus control) as within-subject factors. After stress induction (or control), we probed neural responses to facial expressions using fMRI. During the late luteal phase, negative affect was highest and the stress-induced increase in heart rate was mildly augmented. fMRI data of the control condition replicate previous findings of elevated amygdala and medial prefrontal cortex responses when comparing the late luteal with the late follicular phase. Importantly, stress induction had opposite effects in the two cycle phases, with unexpected lower response magnitudes in the late luteal phase. Moreover, the larger the increase in allopregnanolone concentration across the menstrual cycle was, the smaller the amygdala and medial prefrontal cortex responses were after stress induction in the late luteal phase. Our findings show that moderate psychological stress influences menstrual cycle effects on activity in the emotion regulation circuitry. These results provide potential insights into how fluctuations in allopregnanolone that naturally occur during the menstrual cycle may change stress vulnerability.
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| 6. |
- Svensson, A., et al.
(författare)
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European children's sugar intake on weekdays versus weekends: the IDEFICS study
- 2014
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 68:7, s. 822-828
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare the intake of total sugars, foods and drinks rich in added sugar, and energy in children on weekdays (Monday Thursday), Fridays and weekends. METHODS: Dietary intake (g, kJ, energy %) was assessed using a computerized 24-h recall method in a sample of 2- to 9-year-old children from Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden who were participating in the IDEFICS baseline study (2007-2008). Analyses were performed in 9497 children by selecting one 24-h recall per child (for comparison of weekdays vs weekends, and Fridays vs weekdays and weekends). Selected stratified analyses were performed by country and age group. RESULTS: Intake of total sugars exceeded 20 energy % in all countries but one. In the non-stratified analyses, the intakes of total sugars and foods and drinks rich in added sugar were found to be higher on weekends compared with weekdays (both P < 0.001), and intakes on Fridays were a mix between intakes on weekdays and weekends. Energy intake did not differ between weekdays and weekends. Results were somewhat heterogeneous, both across countries and age groups. CONCLUSIONS: High intake of sugar remains an important nutritional problem in children of many European countries. Interventions aiming to prevent this diet pattern may optimize their impact by targeting dietary habits on Fridays and weekends. Furthermore, when conducting dietary assessment in children, data from weekends and Fridays in combination with a selection of Mondays to Thursdays are needed to capture habitual sugar intake. Age and dietary cultures should also be considered in dietary intervention and assessment as effect modifications were seen for both age and country.
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| 7. |
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| 8. |
- Svensson, Åsa, 1981-, et al.
(författare)
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Observed differences in dietary intake on weekdays versus weekends in European children
- 2012
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Konferensbidrag (refereegranskat)abstract
- OBJECTIVE: To examine differences in intake of energy (EI), sugars, and sucrose-rich foods and drinks between weekdays (Monday through Thursday), Fridays and weekends in European children.METHODS: Twenty-four hour recall data were used for children aged 2-9 years from Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden, participating in the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In children and infantS) study at baseline 2007-2008. Dietary intake was reported by parents and complemented by day-care or school personnel when needed. Children with complete interview days for whom all main meals were known and that had a reported EI between 500-5000 kcal/day were included with one day each. For children with more than one 24-hour recall weekends were chosen over weekdays in order to obtain a balanced distribution of days of week. Regression models adjusted for country, age and sex were performed to investigate differences in EI, sugars (g/day) and sucrose-rich foods and drinks (g/day) on weekdays (Monday through Thursday) versus weekends (n=9339), as well as Fridays versus weekdays and weekends (n=9496), respectively. Models with intake of sugars and sucrose-rich foods and drinks as dependent variables were additionally adjusted for EI. The analysis comparing intake on weekdays versus weekends was stratified by country for Belgium, Cyprus (excluding sugars), Germany, Hungary, Italy, Spain and Sweden.RESULTS: Intake of energy (t(9338)=4.1, p<0.001), sugars (t(8189)=7.6, p<0.001), and sucrose-rich foods and drinks (t(9338)=6.4, p<0.001) were higher on weekends versus weekdays. Intake on Fridays was a cross between the intakes on weekdays and weekends and did not differ from them, except for intake of sucrose-rich foods and drinks, being lower on Fridays compared with weekends (t(9495)= -2.2, p=0.02). Stratified analyses showed higher EI on weekends versus weekdays in Hungary (t(1532)=7.7, p<0.001). Intake of sugars was higher on weekends versus weekdays in Hungary (t(1532)=5.6, p<0.001), Italy (t(1974)=4.5, p<0.001) and Sweden (t(1224)=6.0, p<0.001), but in Belgium it was lower on weekends versus weekdays (t(372)= -2.0, p=0.04). Intake of sucrose rich foods and drinks was higher on weekends versus weekdays in Cyprus (t(1148)=2.8, p=0.01), Hungary (t(1532)=2.9, p=0.004), Italy (t(1974)=9.0, p<0.001) and Spain (t(623)=3.0, P=0.003).CONCLUSION: Dietary intake of European children differed on weekdays (Monday through Thursday) versus weekends, and intake on Fridays was a cross between the intakes on these days. The results imply the importance to capture dietary intake of children on both weekdays and weekends when assessing their habitual intake with 24-hour recalls.
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| 9. |
- van Es, Michael A, et al.
(författare)
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Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
- 2011
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Ingår i: Annals of Neurology. - : Wiley-Blackwell. - 0364-5134 .- 1531-8249. ; 70:6, s. 964-973
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
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