| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
- Davies, G., et al.
(författare)
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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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| 3. |
- Silventoinen, K., et al.
(författare)
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The CODATwins Project : The current status and recent findings of COllaborative Project of Development of Anthropometrical Measures in Twins
- 2019
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 800-808
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Tidskriftsartikel (refereegranskat)abstract
- The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
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| 4. |
- de Schipper, Elles, et al.
(författare)
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Functioning and disability in autism spectrum disorder : A worldwide survey of experts
- 2016
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Ingår i: Autism Research. - : John Wiley & Sons. - 1939-3792 .- 1939-3806. ; 9:9, s. 959-969
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study is the second of four to prepare International Classification of Functioning, Disability and Health (ICF; and Children and Youth version, ICF(-CY)) Core Sets for Autism Spectrum Disorder (ASD).The objective of this study was to survey the opinions and experiences of international experts on functioning and disability in ASD.Methods: Using a protocol stipulated by the World Health Organization (WHO) and monitored by the ICF Research Branch, an email-based questionnaire was circulated worldwide among ASD experts, and meaningful functional ability and disability concepts were extracted from their responses. These concepts were then linked to the ICF(-CY) by two independent researchers using a standardized linking procedure.Results: N = 225 experts from 10 different disciplines and all six WHO-regions completed the survey. Meaningful concepts from the responses were linked to 210 ICF(-CY) categories. Of these, 103 categories were considered most relevant to ASD (i.e., identified by at least 5% of the experts), of which 37 were related toActivities and Participation, 35 to Body functions, 22 to Environmental factors, and 9 to Body structures. A variety of personal characteristics and ASD-related functioning skills were provided by experts, including honesty, loyalty, attention to detail and creative talents. Reported gender differences in ASD comprised more externalizing behaviors among males and more internalizing behaviors in females.Conclusion: The ICF(-CY) categories derived from international expert opinions indicate that the impact of ASD on functioning extends far beyond core symptom domains
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| 5. |
- Jelenkovic, A., et al.
(författare)
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Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994
- 2016
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Ingår i: eLIFE. - Cambridge, United Kingdom : eLife Sciences Publications. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.
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| 6. |
- Lee, Eun-Young, et al.
(författare)
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Play, Learn, and Teach Outdoors—Network (PLaTO-Net) : terminology, taxonomy, and ontology
- 2022
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : BioMed Central (BMC). - 1479-5868. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A recent dialogue in the field of play, learn, and teach outdoors (referred to as “PLaTO” hereafter) demonstrated the need for developing harmonized and consensus-based terminology, taxonomy, and ontology for PLaTO. This is important as the field evolves and diversifies in its approaches, contents, and contexts over time and in different countries, cultures, and settings. Within this paper, we report the systematic and iterative processes undertaken to achieve this objective, which has built on the creation of the global PLaTO-Network (PLaTO-Net). Methods: This project comprised of four major methodological phases. First, a systematic scoping review was conducted to identify common terms and definitions used pertaining to PLaTO. Second, based on the results of the scoping review, a draft set of key terms, taxonomy, and ontology were developed, and shared with PLaTO members, who provided feedback via four rounds of consultation. Third, PLaTO terminology, taxonomy, and ontology were then finalized based on the feedback received from 50 international PLaTO member participants who responded to ≥ 3 rounds of the consultation survey and dialogue. Finally, efforts to share and disseminate project outcomes were made through different online platforms. Results: This paper presents the final definitions and taxonomy of 31 PLaTO terms along with the PLaTO-Net ontology model. The model incorporates other relevant concepts in recognition that all the aspects of the model are interrelated and interconnected. The final terminology, taxonomy, and ontology are intended to be applicable to, and relevant for, all people encompassing various identities (e.g., age, gender, culture, ethnicity, ability). Conclusions: This project contributes to advancing PLaTO-based research and facilitating intersectoral and interdisciplinary collaboration, with the long-term goal of fostering and strengthening PLaTO’s synergistic linkages with healthy living, environmental stewardship, climate action, and planetary health agendas. Notably, PLaTO terminology, taxonomy and ontology will continue to evolve, and PLaTO-Net is committed to advancing and periodically updating harmonized knowledge and understanding in the vast and interrelated areas of PLaTO.
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| 7. |
- Lin, C. -Y, et al.
(författare)
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Longitudinal relationships between nomophobia, addictive use of social media, and insomnia in adolescents
- 2021
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Ingår i: Healthcare. - : MDPI. - 2227-9032. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Temporal relationships between nomophobia (anxiety related to ‘no mobile phone phobia’), addictive use of social media, and insomnia are understudied. The present study aimed to use a longitudinal design to investigate temporal relationships between nomophobia, addictive use of social media, and insomnia among Iranian adolescents; (2) Methods: A total of 1098 adolescents (600 males; 54.6%; age range = 13 to 19) were recruited from 40 randomly selected classes in Qazvin, Iran. They completed baseline assessments. The same cohort was invited to complete three follow-up assessments one month apart. Among the 1098 adolescents, 812 (400 males; 49.3%; age range = 13 to 18) completed the baseline and three follow-up assessments. In each assessment, the participants completed three questionnaires, including the Nomophobia Questionnaire (NMP-Q), Bergen Social Media Addiction Scale (BSMAS), and Insomnia Severity Index (ISI); (3) Results: Multilevel linear mixed-effects regression analyses showed that participants demonstrated increased insomnia longitudinally over 3 months (B = 0.12 and 0.19; p = 0.003 and <0.001). Insomnia was associated with nomophobia (B = 0.20; p < 0.001) and addictive use of social media (B = 0.49; p < 0.001). Nomophobia and addictive use of social media interacted with time in associations with insomnia as demonstrated by significant interaction terms (B = 0.05; p < 0.001 for nomophobia; B = 0.13; p < 0.001 for addictive use of social media); (4) Conclusions: Both nomophobia and addictive use of social media are potential risk factors for adolescent insomnia. The temporal relationship between the three factors suggests that parents, policymakers, and healthcare providers may target reducing nomophobia and addictive use of social media to improve adolescents’ sleep.
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| 8. |
- Rajabi Majd, N., et al.
(författare)
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Efficacy of a Theory-Based Cognitive Behavioral Technique App-Based Intervention for Patients With Insomnia : Randomized Controlled Trial
- 2020
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Ingår i: Journal of Medical Internet Research. - Toronto, ON, Canada : JMIR publications. - 1438-8871. ; 22:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sleep hygiene is important for maintaining good sleep and reducing insomnia. OBJECTIVE: This study examined the long-term efficacy of a theory-based app (including cognitive behavioral therapy [CBT], theory of planned behavior [TPB], health action process approach [HAPA], and control theory [CT]) on sleep hygiene among insomnia patients. METHODS: The study was a 2-arm single-blind parallel-group randomized controlled trial (RCT). Insomnia patients were randomly assigned to a treatment group that used an app for 6 weeks (ie, CBT for insomnia [CBT-I], n=156) or a control group that received only patient education (PE, n=156) through the app. Outcomes were assessed at baseline and 1 month, 3 months, and 6 months postintervention. Primary outcomes were sleep hygiene, insomnia, and sleep quality. Secondary outcomes included attitudes toward sleep hygiene behavior, perceived behavioral control, behavioral intention, action and coping planning, self-monitoring, behavioral automaticity, and anxiety and depression. Linear mixed models were used to evaluate the magnitude of changes in outcomes between the two groups and across time. RESULTS: Sleep hygiene was improved in the CBT-I group compared with the PE group (P=.02 at 1 month, P=.04 at 3 months, and P=.02 at 6 months) as were sleep quality and severity of insomnia. Mediation analyses suggested that perceived behavioral control on sleep hygiene as specified by TPB along with self-regulatory processes from HAPA and CT mediated the effect of the intervention on outcomes. CONCLUSIONS: Health care providers might consider using a CBT-I app to improve sleep among insomnia patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03605732; https://clinicaltrials.gov/ct2/show/NCT03605732.
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| 9. |
- Savage, J. E., et al.
(författare)
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Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:7, s. 912-919
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Tidskriftsartikel (refereegranskat)abstract
- Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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| 10. |
- Silventoinen, Karri, et al.
(författare)
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Education in twins and their parents across birth cohorts over 100 years : an individual-level pooled analysis of 42 twin cohorts
- 2017
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Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
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Tidskriftsartikel (refereegranskat)abstract
- Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
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