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  • 1
    Online Resource
    Online Resource
    Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
    Springer Science and Business Media LLC ; 2022
    In:  Nature Genetics Vol. 54, No. 5 ( 2022-05), p. 581-592
    Details
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 54, No. 5 ( 2022-05), p. 581-592
    Abstract: Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    URL: Article
    DOI: 10.1038/s41588-022-01062-7
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 2
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    Prevalence and correlates of dementia and mild cognitive impairment classified with different versions of the modified Telephone Interview for Cognitive Status (TICS‐m)
    Wiley ; 2019
    In:  International Journal of Geriatric Psychiatry Vol. 34, No. 12 ( 2019-12), p. 1883-1891
    Details
    In: International Journal of Geriatric Psychiatry, Wiley, Vol. 34, No. 12 ( 2019-12), p. 1883-1891
    Abstract: The modified Telephone Interview for Cognitive Status (TICS‐m) is an efficient and cost‐effective screening instrument of dementia, but there is less support for its utility in the detection of mild cognitive impairment (MCI). We undertook a comprehensive evaluation of the utility of different TICS‐m versions with or without an education‐adjusted scoring method to classify dementia and MCI in a large population‐based sample. Methods Cross‐sectional assessment of cognition (TICS‐m), depressive symptoms (CES‐D), and apolipoprotein E (APOE) ε4 status was performed on 1772 older adults (aged 71‐78 y, education 5‐16 y, 50% female) from the population‐based older Finnish Twin Cohort. TICS‐m classification methods with and without education adjustment were used to classify individuals with normal cognition, MCI, or dementia. Results The prevalence of dementia and MCI varied between education‐adjusted (dementia = 3.7%, MCI = 9.3%) and unadjusted classifications (dementia = 8.5%‐11%, MCI = 22.3%‐41.3%). APOE ε4 status was associated with dementia irrespective of education adjustment, but with MCI only when education adjustment was used. Regardless of the version, poorer continuous TICS‐m scores were associated with higher age, lower education, more depressive symptoms, male sex, and being an APOE ε4 carrier. Conclusions We showed that demographic factors, APOE ε4 status, and depressive symptoms were similarly related to continuous TICS‐m scores and dementia classifications with different versions. However, education‐adjusted classification resulted in a lower prevalence of dementia and MCI and in a higher proportion of APOE ε4 allele carriers among those identified as having MCI. Our results support the use of education‐adjusted classification especially in the context of MCI.
    Type of Medium: Online Resource
    ISSN: 0885-6230 , 1099-1166
    URL: Issue
    URL: Article
    DOI: 10.1002/gps.v34.12
    DOI: 10.1002/gps.5205
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1500455-7
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  • 3
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    Continuity of Genetic Risk for Aggressive Behavior Across the Life-Course
    Springer Science and Business Media LLC ; 2021
    In:  Behavior Genetics Vol. 51, No. 5 ( 2021-09), p. 592-606
    Details
    In: Behavior Genetics, Springer Science and Business Media LLC, Vol. 51, No. 5 ( 2021-09), p. 592-606
    Abstract: We test whether genetic influences that explain individual differences in aggression in early life also explain individual differences across the life-course. In two cohorts from The Netherlands ( N  = 13,471) and Australia ( N  = 5628), polygenic scores (PGSs) were computed based on a genome-wide meta-analysis of childhood/adolescence aggression. In a novel analytic approach, we ran a mixed effects model for each age (Netherlands: 12–70 years, Australia: 16–73 years), with observations at the focus age weighted as 1, and decaying weights for ages further away. We call this approach a ‘rolling weights’ model. In The Netherlands, the estimated effect of the PGS was relatively similar from age 12 to age 41, and decreased from age 41–70. In Australia, there was a peak in the effect of the PGS around age 40 years. These results are a first indication from a molecular genetics perspective that genetic influences on aggressive behavior that are expressed in childhood continue to play a role later in life.
    Type of Medium: Online Resource
    ISSN: 0001-8244 , 1573-3297
    URL: Article
    DOI: 10.1007/s10519-021-10076-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2014974-8
    SSG: 12
    SSG: 5,2
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  • 4
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    Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
    Elsevier BV ; 2022
    In:  Journal of the American Academy of Child & Adolescent Psychiatry Vol. 61, No. 7 ( 2022-07), p. 934-945
    Details
    In: Journal of the American Academy of Child & Adolescent Psychiatry, Elsevier BV, Vol. 61, No. 7 ( 2022-07), p. 934-945
    Type of Medium: Online Resource
    ISSN: 0890-8567
    URL: Article
    DOI: 10.1016/j.jaac.2021.11.035
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2022051-0
    SSG: 5,2
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  • 5
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    A Polygenic Risk Score for Hand Grip Strength Predicts Muscle Strength and Proximal and Distal Functional Outcomes among Older Women
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Medicine & Science in Sports & Exercise Vol. 54, No. 11 ( 2022-11), p. 1889-1896
    Details
    In: Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 11 ( 2022-11), p. 1889-1896
    Abstract: Hand grip strength (HGS) is a widely used indicator of overall muscle strength and general health. We computed a polygenic risk score (PRS) for HGS and examined whether it predicted muscle strength, functional capacity, and disability outcomes. Methods Genomewide association study summary statistics for HGS from the Pan-UK Biobank was used. PRS were calculated in the Finnish Twin Study on Aging ( N = 429 women, 63–76 yr). Strength tests included HGS, isometric knee extension, and ankle plantarflexion strength. Functional capacity was examined with the Timed Up and Go, 6-min and 10-m walk tests, and dual-task tests. Disabilities in the basic activities of daily living (ADL) and instrumental ADL (IADL) were investigated with questionnaires. The proportion of variation in outcomes accounted for by PRS HGS was examined using linear mixed models and extended logistic regression. Results The measured HGS increased linearly over increasing PRS ( β = 4.8, SE = 0.93, P 〈 0.001). PRS HGS independently accounted for 6.1% of the variation in the measured HGS ( β = 14.2, SE = 3.1, P 〈 0.001), 5.4% of the variation in knee extension strength ( β = 19.6, SE = 4.7, P 〈 0.001), 1.2% of the variation in ankle plantarflexion strength ( β = 9.4, SE = 4.2, P = 0.027), and 0.1%–1.5% of the variation in functional capacity tests ( P = 0.016–0.133). Further, participants with higher PRS HGS were less likely to have ADL/IADL disabilities (odds ratio = 0.74–0.76). Conclusions Older women with genetic risk for low muscle strength were significantly weaker than those with genetic susceptibility for high muscle strength. PRS HGS was also systematically associated with overall muscle strength and proximal and distal functional outcomes that require muscle strength.
    Type of Medium: Online Resource
    ISSN: 1530-0315 , 0195-9131
    URL: Article
    DOI: 10.1249/MSS.0000000000002981
    RVK:
    ZX 1000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2031167-9
    SSG: 31
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  • 6
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    Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
    Springer Science and Business Media LLC ; 2018
    In:  Nature Communications Vol. 9, No. 1 ( 2018-05-29)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2018-05-29)
    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.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-018-04362-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2553671-0
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  • 7
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    The Associations Between Leisure-Time Physical Activity and Academic Performance: A Twin Study
    Human Kinetics ; 2021
    In:  Journal of Physical Activity and Health Vol. 18, No. 8 ( 2021-08-1), p. 998-1003
    Details
    In: Journal of Physical Activity and Health, Human Kinetics, Vol. 18, No. 8 ( 2021-08-1), p. 998-1003
    Abstract: Background : Both genetic and environmental influences have been shown to contribute to the association between physical activity and overall academic performance. The authors examined whether leisure-time physical activity (LTPA) shares genetic and environmental variances between spelling, essay writing, reading aloud, reading comprehension, and mathematics in early adolescence. Moreover, they investigated whether genetic polymorphisms associated with physical activity behavior affect these academic skills. Methods : Participants were 12-year-old Finnish twins (n = 4356–4370 twins/academic skill, 49% girls). Academic skills were assessed by teachers, and LTPA was self-reported. Polygenic scores for physical activity behavior were constructed from the UK Biobank. Quantitative genetic modeling and linear regression models were used to analyze the data. Results : The trait correlations between LTPA and academic skills were significant but weak ( r  = .05–.08). The highest trait correlation was found between LTPA and mathematics. A significant genetic correlation was revealed between LTPA and essay writing ( r A  = .14). Regarding polygenic scores of physical activity, the highest correlations were found with reading comprehension, spelling, and essay writing, but these results only approached statistical significance ( P values = .09–.15). Conclusions : The authors’ results suggest that reading and writing are the academic skills that most likely share a common genetic background with LTPA.
    Type of Medium: Online Resource
    ISSN: 1543-3080 , 1543-5474
    URL: Article
    DOI: 10.1123/jpah.2020-0746
    Language: Unknown
    Publisher: Human Kinetics
    Publication Date: 2021
    SSG: 31
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  • 8
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    Genomic prediction of alcohol-related morbidity and mortality
    Springer Science and Business Media LLC ; 2020
    In:  Translational Psychiatry Vol. 10, No. 1 ( 2020-01-21)
    Details
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-01-21)
    Abstract: While polygenic risk scores (PRS) have been shown to predict many diseases and risk factors, the potential of genomic prediction in harm caused by alcohol use has not yet been extensively studied. Here, we built a novel polygenic risk score of 1.1 million variants for alcohol consumption and studied its predictive capacity in 96,499 participants from the FinnGen study and 39,695 participants from prospective cohorts with detailed baseline data and up to 25 years of follow-up time. A 1 SD increase in the PRS was associated with 11.2 g (=0.93 drinks) higher weekly alcohol consumption (CI = 9.85–12.58 g, p  = 2.3 × 10 –58 ). The PRS was associated with alcohol-related morbidity (4785 incident events) and the risk estimate between the highest and lowest quintiles of the PRS was 1.83 (95% CI = 1.66–2.01, p  = 1.6 × 10 –36 ). When adjusted for self-reported alcohol consumption, education, marital status, and gamma-glutamyl transferase blood levels in 28,639 participants with comprehensive baseline data from prospective cohorts, the risk estimate between the highest and lowest quintiles of the PRS was 1.58 (CI = 1.26–1.99, p  = 8.2 × 10 –5 ). The PRS was also associated with all-cause mortality with a risk estimate of 1.33 between the highest and lowest quintiles (CI = 1.20–1.47, p  = 4.5 × 10 –8 ) in the adjusted model. In conclusion, the PRS for alcohol consumption independently associates for both alcohol-related morbidity and all-cause mortality. Together, these findings underline the importance of heritable factors in alcohol-related health burden while highlighting how measured genetic risk for an important behavioral risk factor can be used to predict related health outcomes.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    URL: Article
    DOI: 10.1038/s41398-019-0676-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2609311-X
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  • 9
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    Genetic association study of childhood aggression across raters, instruments, and age
    Springer Science and Business Media LLC ; 2021
    In:  Translational Psychiatry Vol. 11, No. 1 ( 2021-07-30)
    Details
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-07-30)
    Abstract: Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG overall ) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG overall . The gene-based analysis returned three significant genes: ST3GAL3 ( P  = 1.6E–06), PCDH7 ( P  = 2.0E–06), and IPO13 ( P  = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations ( r g ) among rater-specific assessment of AGG ranged from r g  = 0.46 between self- and teacher-assessment to r g  = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong r g s with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range $$\left| {r_g} \right|$$ r g : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation ( r g  = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range $$\left| {r_g} \right|$$ r g : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    URL: Article
    DOI: 10.1038/s41398-021-01480-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2609311-X
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  • 10
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    Higher aggression is related to poorer academic performance in compulsory education
    Wiley ; 2021
    In:  Journal of Child Psychology and Psychiatry Vol. 62, No. 3 ( 2021-03), p. 327-338
    Details
    In: Journal of Child Psychology and Psychiatry, Wiley, Vol. 62, No. 3 ( 2021-03), p. 327-338
    Abstract: To conduct a comprehensive assessment of the association between aggression and academic performance in compulsory education. Method We studied aggression and academic performance in over 27,000 individuals from four European twin cohorts participating in the ACTION consortium (Aggression in Children: Unraveling gene‐environment interplay to inform Treatment and InterventiON strategies). Individual level data on aggression at ages 7–16 were assessed by three instruments (Achenbach System of Empirically Based Assessment, Multidimensional Peer Nomination Inventory, Strengths and Difficulties Questionnaire) including parental, teacher and self‐reports. Academic performance was measured with teacher‐rated grade point averages (ages 12–14) or standardized test scores (ages 12–16). Random effect meta‐analytical correlations with academic performance were estimated for parental ratings (in all four cohorts) and self‐ratings (in three cohorts). Results All between‐family analyses indicated significant negative aggression–academic performance associations with correlations ranging from −.06 to −.33. Results were similar across different ages, instruments and raters and either with teacher‐rated grade point averages or standardized test scores as measures of academic performance. Meta‐analytical r ’s were −.20 and −.23 for parental and self‐ratings, respectively. In within‐family analyses of all twin pairs, the negative aggression–academic performance associations were statistically significant in 14 out of 17 analyses ( r  = −.17 for parental‐ and r  = −.16 for self‐ratings). Separate analyses in monozygotic ( r  = −.07 for parental and self‐ratings), same‐sex dizygotic ( r ’s = −.16 and −.17 for parental and self‐ratings) and opposite‐sex dizygotic ( r ’s = −.21 and −.19 for parental and self‐ratings) twin pairs suggested partial confounding by genetic effects. Conclusions There is a robust negative association between aggression and academic performance in compulsory education. Part of these associations were explained by shared genetic effects, but some evidence of a negative association between aggression and academic performance remained even in within‐family analyses of monozygotic twin pairs.
    Type of Medium: Online Resource
    ISSN: 0021-9630 , 1469-7610
    URL: Issue
    URL: Article
    DOI: 10.1111/jcpp.v62.3
    DOI: 10.1111/jcpp.13273
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1470297-6
    SSG: 5,2
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