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  1. Article ; Online: Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response

    Jelle Vlaanderen / Roel Vermeulen / Matthew Whitaker / Marc Chadeau-Hyam / Jouke-Jan Hottenga / Eco de Geus / Gonneke Willemsen / Brenda W.J.H. Penninx / Rick Jansen / Dorret I. Boomsma

    Environment International, Vol 168, Iss , Pp 107491- (2022)

    2022  

    Abstract: Background: Exposure to ambient air pollution, even at low levels, is a major environmental health risk. The peripheral blood transcriptome provides a potential avenue for the elucidation of ambient air pollution related biological perturbations. We ... ...

    Abstract Background: Exposure to ambient air pollution, even at low levels, is a major environmental health risk. The peripheral blood transcriptome provides a potential avenue for the elucidation of ambient air pollution related biological perturbations. We assessed the association between long-term estimates for seven priority air pollutants and perturbations in peripheral blood transcriptomics data collected in the Dutch National Twin Register (NTR) and Netherlands Study of Depression and Anxiety (NESDA) cohorts. Methods: In both the discovery (n = 2438) and replication (n = 1567) cohort, outdoor concentration of 7 air pollutants (NO2, NOx, particulate matter (PM2.5, PM2.5abs, PM10, PMcoarse), and ultrafine particles) was predicted with land use regression models. Gene expression was assessed by Affymetrix U219 arrays. Multi-variable univariate mixed-effect models were applied to test for an association between the air pollutants and the transcriptome. Functional analysis was conducted in DAVID. Results: In the discovery cohort, we observed for 335 genes (374 probes with FDR < 5 %) a perturbation in peripheral blood gene expression that was associated with long-term average levels of PM2.5. For 69 genes pooled effect estimates from the NTR and NESDA cohorts were significant. Identified genes play a role in biological pathways related to cell signaling and immune response. Sixty-two out of 69 genes had a similar direction of effect in an analysis in which we regressed the probes on differential PM2.5 exposure within monozygotic twin pairs, indicating that the observed differences in gene expression were likely driven by differences in air pollution, rather than by confounding by genetic factors. Conclusion: Our results indicate that PM2.5 can elicit a response in cell signaling and the immune system, both hallmarks of environmental diseases. The differential effect that we observed between air pollutants may aid in the understanding of differential health effects that have been observed with these exposures.
    Keywords Air pollution ; Transcriptomics ; Molecular epidemiology ; Biological pathways ; Cell signaling ; Immune system ; Environmental sciences ; GE1-350
    Subject code 333
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Large-scale GWAS of food liking reveals genetic determinants and genetic correlations with distinct neurophysiological traits

    Sebastian May-Wilson / Nana Matoba / Kaitlin H. Wade / Jouke-Jan Hottenga / Maria Pina Concas / Massimo Mangino / Eryk J. Grzeszkowiak / Cristina Menni / Paolo Gasparini / Nicholas J. Timpson / Maria G. Veldhuizen / Eco de Geus / James F. Wilson / Nicola Pirastu

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 13

    Abstract: Genetic determinants of food consumption and food liking are likely to be distinct, although it has not been well studied. Here, the authors identify genetic variants associated with food-liking, finding that different food-liking traits correlate with ... ...

    Abstract Genetic determinants of food consumption and food liking are likely to be distinct, although it has not been well studied. Here, the authors identify genetic variants associated with food-liking, finding that different food-liking traits correlate with different brain areas and other food consumption traits.
    Keywords Science ; Q
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores

    Perline A. Demange / Jouke Jan Hottenga / Abdel Abdellaoui / Espen Moen Eilertsen / Margherita Malanchini / Benjamin W. Domingue / Emma Armstrong-Carter / Eveline L. de Zeeuw / Kaili Rimfeld / Dorret I. Boomsma / Elsje van Bergen / Gerome Breen / Michel G. Nivard / Rosa Cheesman

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 14

    Abstract: Understanding how parents’ cognitive and non-cognitive skills influence their children’s educational trajectories is important for educational, family and economic policy. Here, the authors investigate parental influence on children’s education using ... ...

    Abstract Understanding how parents’ cognitive and non-cognitive skills influence their children’s educational trajectories is important for educational, family and economic policy. Here, the authors investigate parental influence on children’s education using genetic approaches.
    Keywords Science ; Q
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Implementation and implications for polygenic risk scores in healthcare

    John L. Slunecka / Matthijs D. van der Zee / Jeffrey J. Beck / Brandon N. Johnson / Casey T. Finnicum / René Pool / Jouke-Jan Hottenga / Eco J. C. de Geus / Erik A. Ehli

    Human Genomics, Vol 15, Iss 1, Pp 1-

    2021  Volume 18

    Abstract: Abstract Increasing amounts of genetic data have led to the development of polygenic risk scores (PRSs) for a variety of diseases. These scores, built from the summary statistics of genome-wide association studies (GWASs), are able to stratify ... ...

    Abstract Abstract Increasing amounts of genetic data have led to the development of polygenic risk scores (PRSs) for a variety of diseases. These scores, built from the summary statistics of genome-wide association studies (GWASs), are able to stratify individuals based on their genetic risk of developing various common diseases and could potentially be used to optimize the use of screening and preventative treatments and improve personalized care for patients. Many challenges are yet to be overcome, including PRS validation, healthcare professional and patient education, and healthcare systems integration. Ethical challenges are also present in how this information is used and the current lack of diverse populations with PRSs available. In this review, we discuss the topics above and cover the nature of PRSs, visualization schemes, and how PRSs can be improved. With these tools on the horizon for multiple diseases, scientists, clinicians, health systems, regulatory bodies, and the public should discuss the uses, benefits, and potential risks of PRSs.
    Keywords Polygenic risk score ; PRS ; Clinical genetics ; Genetic risk ; Risk stratification ; Public health ; Medicine ; R ; Genetics ; QH426-470
    Subject code 170
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Genome-wide association meta-analysis identifies 29 new acne susceptibility loci

    Brittany L. Mitchell / Jake R. Saklatvala / Nick Dand / Fiona A. Hagenbeek / Xin Li / Josine L. Min / Laurent Thomas / Meike Bartels / Jouke Jan Hottenga / Michelle K. Lupton / Dorret I. Boomsma / Xianjun Dong / Kristian Hveem / Mari Løset / Nicholas G. Martin / Jonathan N. Barker / Jiali Han / Catherine H. Smith / Miguel E. Rentería /
    Michael A. Simpson

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 9

    Abstract: Better understanding of the genetic basis of acne can pave the way to more effective treatments. Here, the authors perform a genome-wide association study meta-analysis of >20,000 cases and identify 29 new acne susceptibility loci, uncovering genetic ... ...

    Abstract Better understanding of the genetic basis of acne can pave the way to more effective treatments. Here, the authors perform a genome-wide association study meta-analysis of >20,000 cases and identify 29 new acne susceptibility loci, uncovering genetic links to Mendelian hair and skin disorders and other complex traits.
    Keywords Science ; Q
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: DNA methylation in peripheral tissues and left-handedness

    Veronika V. Odintsova / Matthew Suderman / Fiona A. Hagenbeek / Doretta Caramaschi / Jouke-Jan Hottenga / René Pool / BIOS Consortium / Conor V. Dolan / Lannie Ligthart / Catharina E. M. van Beijsterveldt / Gonneke Willemsen / Eco J. C. de Geus / Jeffrey J. Beck / Erik A. Ehli / Gabriel Cuellar-Partida / David M. Evans / Sarah E. Medland / Caroline L. Relton / Dorret I. Boomsma /
    Jenny van Dongen

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 16

    Abstract: Abstract Handedness has low heritability and epigenetic mechanisms have been proposed as an etiological mechanism. To examine this hypothesis, we performed an epigenome-wide association study of left-handedness. In a meta-analysis of 3914 adults of whole- ...

    Abstract Abstract Handedness has low heritability and epigenetic mechanisms have been proposed as an etiological mechanism. To examine this hypothesis, we performed an epigenome-wide association study of left-handedness. In a meta-analysis of 3914 adults of whole-blood DNA methylation, we observed that CpG sites located in proximity of handedness-associated genetic variants were more strongly associated with left-handedness than other CpG sites (P = 0.04), but did not identify any differentially methylated positions. In longitudinal analyses of DNA methylation in peripheral blood and buccal cells from children (N = 1737), we observed moderately stable associations across age (correlation range [0.355–0.578]), but inconsistent across tissues (correlation range [− 0.384 to 0.318]). We conclude that DNA methylation in peripheral tissues captures little of the variance in handedness. Future investigations should consider other more targeted sources of tissue, such as the brain.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Heritability and Genome-Wide Association Studies for Hair Color in a Dutch Twin Family Based Sample

    Bochao Danae Lin / Hamdi Mbarek / Gonneke Willemsen / Conor V. Dolan / Iryna O. Fedko / Abdel Abdellaoui / Eco J. de Geus / Dorret I. Boomsma / Jouke-Jan Hottenga

    Genes, Vol 6, Iss 3, Pp 559-

    2015  Volume 576

    Abstract: Hair color is one of the most visible and heritable traits in humans. Here, we estimated heritability by structural equation modeling (N = 20,142), and performed a genome wide association (GWA) analysis (N = 7091) and a GCTA study (N = 3340) on hair ... ...

    Abstract Hair color is one of the most visible and heritable traits in humans. Here, we estimated heritability by structural equation modeling (N = 20,142), and performed a genome wide association (GWA) analysis (N = 7091) and a GCTA study (N = 3340) on hair color within a large cohort of twins, their parents and siblings from the Netherlands Twin Register (NTR). Self-reported hair color was analyzed as five binary phenotypes, namely “blond versus non-blond”, “red versus non-red”, “brown versus non-brown”, “black versus non-black”, and “light versus dark”. The broad-sense heritability of hair color was estimated between 73% and 99% and the genetic component included non-additive genetic variance. Assortative mating for hair color was significant, except for red and black hair color. From GCTA analyses, at most 24.6% of the additive genetic variance in hair color was explained by 1000G well-imputed SNPs. Genome-wide association analysis for each hair color showed that SNPs in the MC1R region were significantly associated with red, brown and black hair, and also with light versus dark hair color. Five other known genes (HERC2, TPCN2, SLC24A4, IRF4, and KITLG) gave genome-wide significant hits for blond, brown and light versus dark hair color. We did not find and replicate any new loci for hair color.
    Keywords hair color ; twin-family based heritability ; GRM based heritability ; Genome Wide Association Study ; Genetics ; QH426-470 ; Biology (General) ; QH301-705.5 ; Science ; Q
    Subject code 660 ; 571
    Language English
    Publishing date 2015-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: A genome-wide association study of total child psychiatric problems scores.

    Alexander Neumann / Ilja M Nolte / Irene Pappa / Tarunveer S Ahluwalia / Erik Pettersson / Alina Rodriguez / Andrew Whitehouse / Catharina E M van Beijsterveldt / Beben Benyamin / Anke R Hammerschlag / Quinta Helmer / Ville Karhunen / Eva Krapohl / Yi Lu / Peter J van der Most / Teemu Palviainen / Beate St Pourcain / Ilkka Seppälä / Anna Suarez /
    Natalia Vilor-Tejedor / Carla M T Tiesler / Carol Wang / Amanda Wills / Ang Zhou / Silvia Alemany / Hans Bisgaard / Klaus Bønnelykke / Gareth E Davies / Christian Hakulinen / Anjali K Henders / Elina Hyppönen / Jakob Stokholm / Meike Bartels / Jouke-Jan Hottenga / Joachim Heinrich / John Hewitt / Liisa Keltikangas-Järvinen / Tellervo Korhonen / Jaakko Kaprio / Jari Lahti / Marius Lahti-Pulkkinen / Terho Lehtimäki / Christel M Middeldorp / Jackob M Najman / Craig Pennell / Chris Power / Albertine J Oldehinkel / Robert Plomin / Katri Räikkönen / Olli T Raitakari

    PLoS ONE, Vol 17, Iss 8, p e

    2022  Volume 0273116

    Abstract: Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide ...

    Abstract Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

    Fiona A. Hagenbeek / René Pool / Jenny van Dongen / Harmen H. M. Draisma / Jouke Jan Hottenga / Gonneke Willemsen / Abdel Abdellaoui / Iryna O. Fedko / Anouk den Braber / Pieter Jelle Visser / Eco J. C. N. de Geus / Ko Willems van Dijk / Aswin Verhoeven / H. Eka Suchiman / Marian Beekman / P. Eline Slagboom / Cornelia M. van Duijn / BBMRI Metabolomics Consortium / Amy C. Harms /
    Thomas Hankemeier / Meike Bartels / Michel G. Nivard / Dorret I. Boomsma

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: Blood metabolite levels are under the influence of environmental and genetic factors. Here, Hagenbeek et al. perform heritability estimations for metabolite measures and determine the contribution of known metabolite loci to metabolite levels using data ... ...

    Abstract Blood metabolite levels are under the influence of environmental and genetic factors. Here, Hagenbeek et al. perform heritability estimations for metabolite measures and determine the contribution of known metabolite loci to metabolite levels using data from 40 genome-wide association studies.
    Keywords Science ; Q
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Author Correction

    Fiona A. Hagenbeek / René Pool / Jenny van Dongen / H. M. Draisma / Jouke Jan Hottenga / Gonneke Willemsen / Abdel Abdellaoui / Iryna O. Fedko / Anouk den Braber / Pieter Jelle Visser / Eco J. C. N. de Geus / Ko Willems van Dijk / Aswin Verhoeven / H. Eka Suchiman / Marian Beekman / P. Eline Slagboom / Cornelia M. van Duijn / BBMRI Metabolomics Consortium / Amy C. Harms /
    Thomas Hankemeier / Meike Bartels / Michel G. Nivard / Dorret I. Boomsma

    Nature Communications, Vol 11, Iss 1, Pp 1-

    Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

    2020  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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