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Träfflista för sökning "WFRF:(Vonk Judith M.) ;pers:(Boomsma Dorret I.)"

Sökning: WFRF:(Vonk Judith M.) > Boomsma Dorret I.

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1.
  • Middeldorp, Christel M., et al. (författare)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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2.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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3.
  • Smith, Jennifer A, et al. (författare)
  • Genome-wide association study identifies 74 loci associated with educational attainment
  • 2016
  • Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
  • Tidskriftsartikel (refereegranskat)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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4.
  • Vogelezang, Suzanne, et al. (författare)
  • Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
  • 2020
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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5.
  • Ferreira, Manuel A R, et al. (författare)
  • Eleven loci with new reproducible genetic associations with allergic disease risk.
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 143:2, s. 691-699
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities.OBJECTIVE: We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects.METHODS: We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study.RESULTS: Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10-6. Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress TH2 responses.CONCLUSION: Using a gene-based approach, we identified 11 risk loci for allergic disease that were not reported in previous GWASs. Functional studies that investigate the contribution of the 19 associated genes to the pathophysiology of allergic disease and assess their therapeutic potential are warranted.
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Vonk, Judith M (5)
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