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12 results on '"Suchiman, H.E."'

3. TCTEX1D1 is a genetic modifier of disease progression in Duchenne muscular dystrophy

Author

Spitali, P., Zaharieva, I., Bohringer, S., Hiller, M., Chaouch, A., Roos, A., Scotton, C., Claustres, M., Bello, L., McDonald, C.M., Hoffman, E.P., Koeks, Z., Suchiman, H.E., Cirak, S., Scoto, M., Reza, M., Hoen, P.A.C. t, Niks, E.H., Tuffery-Giraud, S., Lochmuller, H., Ferlini, A., Muntoni, F., Aartsma-Rus, A., Dubrovsky, A., Kornberg, A., North, K., Ryan, M., Webster, R., Biggar, W.D., McAdam, L.C., Mah, J.K., Kolski, H., Vishwanathan, V., Chidambaranathan, S., Nevo, Y., Gorni, K., Carlo, J., Tulinius, M., Lotze, T., Bertorini, T.E., Day, J.W., Karachunski, P., Clemens, P.R., Abdel-Hamid, H., Teasley, J., Kuntz, N., Driscoll, S., Bodensteiner, J.B., Connolly, A.M., Pestronk, A., Abresch, R.T., Henricson, E.K., Joyce, N.C., Cnaan, A., Gordish-Dressmsn, H., Morgenroth, L.P., Leshner, R., Tesi-Rocha, C., Thangarajh, M., Duong, T., CINRG Investigators, Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universita degli Studi di Padova, Newcastle University [Newcastle], Department of Reproduction and Growth, UOL of Medical Genetics (University Hospital St Anna, Ferrara), University of Ferrara at St. Anna Hospital, Dubowitz Neuromuscular Center, Institute of Child Health, and Human Genetics

Subjects
Male, 0301 basic medicine, Adolescent, Duchenne muscular dystrophy, [SDV]Life Sciences [q-bio], Locus (genetics), Polymorphism, Single Nucleotide, Genome-wide association studies, Article, Prognostic markers, 03 medical and health sciences, Exon, 0302 clinical medicine, Genotype, Genetics, medicine, Humans, Allele, Muscular dystrophy, Child, Genetics (clinical), Genes, Modifier, biology, business.industry, Neuromuscular disease, medicine.disease, Muscular Dystrophy, Duchenne, Phenotype, 030104 developmental biology, Disease Progression, biology.protein, Human genome, Dystrophin, business, 030217 neurology & neurosurgery
Abstract

Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene leading to the lack of dystrophin. Variability in the disease course suggests that other factors influence disease progression. With this study we aimed to identify genetic factors that may account for some of the variability in the clinical presentation. We compared whole-exome sequencing (WES) data in 27 DMD patients with extreme phenotypes to identify candidate variants that could affect disease progression. Validation of the candidate SNPs was performed in two independent cohorts including 301 (BIO-NMD cohort) and 109 (CINRG cohort of European ancestry) DMD patients, respectively. Variants in the Tctex1 domain containing 1 (TCTEX1D1) gene on chromosome 1 were associated with age of ambulation loss. The minor alleles of two independent variants, known to affect TCTEX1D1 coding sequence and induce skipping of its exon 4, were associated with earlier loss of ambulation. Our data show that disease progression of DMD is affected by a new locus on chromosome 1 and demonstrate the possibility to identify genetic modifiers in rare diseases by studying WES data in patients with extreme phenotypes followed by multiple layers of validation.

Published
2020
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4. Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Author

Hagenbeek, F.A., Pool, R., Dongen, J. van, Draisma, H.H.M., Hottenga, J.J., Willemsen, G., Abdellaoui, A., Fedko, I.O., Braber, A. den, Visser, P.J., Geus, E.J.C.N. de, Dijk, K.W. van, Verhoeven, A., Suchiman, H.E., Beekman, M., Slagboom, P.E., Duijn, C.M. van, Harms, A.C., Hankemeier, T., Bartels, M., Nivard, M.G., Boomsma, D.I., Wolf, J.J.H.B., Cats, D., Amin, N., Beulens, J.W., Bom, J.A. van der, Bomer, N., Demirkan, A., Hilten, J.A. van, Meessen, J.M.T.A., Moed, M.H., Fu, J., Onderwater, G.L.J., Rutters, F., So-Osman, C., Flier, W.M. van der, Heijden, A.A.W.A. van der, Spek, A. van der, Asselbergs, F.W., Boersma, E., Elders, P.M., Geleijnse, J.M., Ikram, M.A., Kloppenburg, M., Meulenbelt, I., Mooijaart, S.P., Nelissen, R.G.H.H., Netea, M.G., Penninx, B.W.J.H., Stehouwer, C.D.A., Teunissen, C.E., Terwindt, G.M., Hart, L.M. 't, Maagdenberg, A.M.J.M. van den, Harst, P. van der, Horst, I.C.C. van der, Kallen, C.J.H. van der, Greevenbroek, M.M.J. van, Spil, W.E. van, Wijmenga, C., Zwinderman, A.H., Zhernikova, A., Jukema, J.W., Mei, H., Slofstra, M., Swertz, M., Akker, E.B. van den, Deelen, J., Reinders, M.J.T., BBMRI Metabolomics Consortium, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Cardiovascular Centre (CVC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Neurology, Epidemiology and Data Science, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, General practice, APH - Methodology, Amsterdam Reproduction & Development (AR&D), APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, Laboratory Medicine, Other Research, APH - Aging & Later Life, APH - Personalized Medicine, APH - Digital Health, ACS - Diabetes & metabolism, Adult Psychiatry, Epidemiology, Cardiology, Radiology & Nuclear Medicine, Biological Psychology, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), Interne Geneeskunde, MUMC+: Centrum voor Chronische Zieken (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), MUMC+: MA Endocrinologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Hematologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Reumatologie (9), and RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome

Subjects
Netherlands Twin Register (NTR), 0301 basic medicine, SELECTION, Quantitative trait loci, Nutrition and Disease, DATABASE, Metabolite, Science, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], General Physics and Astronomy, Genome-wide association study, VARIANCE-ESTIMATION, Biology, Quantitative trait locus, GENOTYPE IMPUTATION, METABOLOMICS, BIOBANK, Genome-wide association studies, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Metabolomics, All institutes and research themes of the Radboud University Medical Center, Missing heritability problem, MISSING HERITABILITY, Voeding en Ziekte, Genetic variation, Life Science, NETHERLANDS TWIN REGISTER, lcsh:Science, VLAG, Genetics, Multidisciplinary, General Chemistry, Heritability, Genetic architecture, 030104 developmental biology, chemistry, Lipidomics, lcsh:Q, 030217 neurology & neurosurgery
Abstract

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes., 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.

Published
2020
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5. Author Correction: Heritability estimates for 361 blood metabolites across 40 genome-wide association studies (Nature Communications, (2020), 11, 1, (39), 10.1038/s41467-019-13770-6)

Author

Hagenbeek, F.A. (Fiona A.), Pool, R. (Reńe), Dongen, J. (Jenny) van, Draisma, G. (Gerrit), Hottenga, J.J. (Jouke Jan), Willemsen, G. (Gonneke), Abdellaoui, A. (Abdel), Fedko, I.O. (Iryna O.), Braber, A. (Anouk) den, Visser, P. (Pim), Geus, E.J.C. (Eco) de, Willems van Dijk, K. (Ko), Verhoeven, A. (Aswin), Suchiman, H.E. (H. Eka), Beekman, M. (Marian), Slagboom, P.E. (Eline), Duijn, C.M. (Cornelia) van, Barkey Wolf, J.J.H. (J. J.H.), Cats, D. (D.), Amin, N. (N.), Beulens, J.W.J. (Joline), van der Bom, J.A. (J. A.), Bomer, N. (Nils), Demirkan, A. (Ayşe), van Hilten, J.A. (J. A.), Meessen, J.M.T.A. (J. M.T.A.), Moed, H. (Heleen), Fu, J. (J.), Onderwater, G.L.J. (G. L.J.), Rutters, F. (F.), So-Osman, C. (Cynthia), van der Flier, W.M. (W. M.), Heijden, A.A.W.A. (Amber A. W.) van der, Spek, A. (Ashley) van der, Asselbergs, F.W. (F. W.), Boersma, H. (Eric), Elders, P.M. (P. M.), Geleijnse, J.M. (J. M.), Ikram, M.A. (Arfan), Kloppenburg, M. (Margreet), Meulenbelt, I. (I.), Mooijaart, S.P. (Simon), Nelissen, R.G.H.H. (Rob), Netea, M.G. (Mihai), Penninx, B.W.J.H. (Brenda), Stehouwer, C.D.A. (C. D.A.), Teunissen, C.E. (Charlotte), Terwindt, G.M. (G. M.), ‘t Hart, L.M. (L. M.), van den Maagdenberg, A.M.J.M. (A. M.J.M.), Harst, P. (Pim) van der, van der Horst, I.C.C. (I. C.C.), Kallen, C.J. van der, van Greevenbroek, M.M.J. (M. M.J.), Spil, W.E. (Willem) van, Wijmenga, C. (Cisca), Zwinderman, A.H. (Ailko), Zhernikova, A. (A.), Jukema, J.W. (Jan Wouter), Mei, H. (H.), Slofstra, M. (M.), Swertz, M. (M.), Akker, E.B. (Erik) van den, Deelen, J. (Joris), Reinders, M.J.T. (M. J.T.), Harms, A.C. (Amy), Hankemeier, T. (Thomas), Bartels, M. (Meike), Nivard, M. (Michel), Boomsma, D.I. (Dorret), Hagenbeek, F.A. (Fiona A.), Pool, R. (Reńe), Dongen, J. (Jenny) van, Draisma, G. (Gerrit), Hottenga, J.J. (Jouke Jan), Willemsen, G. (Gonneke), Abdellaoui, A. (Abdel), Fedko, I.O. (Iryna O.), Braber, A. (Anouk) den, Visser, P. (Pim), Geus, E.J.C. (Eco) de, Willems van Dijk, K. (Ko), Verhoeven, A. (Aswin), Suchiman, H.E. (H. Eka), Beekman, M. (Marian), Slagboom, P.E. (Eline), Duijn, C.M. (Cornelia) van, Barkey Wolf, J.J.H. (J. J.H.), Cats, D. (D.), Amin, N. (N.), Beulens, J.W.J. (Joline), van der Bom, J.A. (J. A.), Bomer, N. (Nils), Demirkan, A. (Ayşe), van Hilten, J.A. (J. A.), Meessen, J.M.T.A. (J. M.T.A.), Moed, H. (Heleen), Fu, J. (J.), Onderwater, G.L.J. (G. L.J.), Rutters, F. (F.), So-Osman, C. (Cynthia), van der Flier, W.M. (W. M.), Heijden, A.A.W.A. (Amber A. W.) van der, Spek, A. (Ashley) van der, Asselbergs, F.W. (F. W.), Boersma, H. (Eric), Elders, P.M. (P. M.), Geleijnse, J.M. (J. M.), Ikram, M.A. (Arfan), Kloppenburg, M. (Margreet), Meulenbelt, I. (I.), Mooijaart, S.P. (Simon), Nelissen, R.G.H.H. (Rob), Netea, M.G. (Mihai), Penninx, B.W.J.H. (Brenda), Stehouwer, C.D.A. (C. D.A.), Teunissen, C.E. (Charlotte), Terwindt, G.M. (G. M.), ‘t Hart, L.M. (L. M.), van den Maagdenberg, A.M.J.M. (A. M.J.M.), Harst, P. (Pim) van der, van der Horst, I.C.C. (I. C.C.), Kallen, C.J. van der, van Greevenbroek, M.M.J. (M. M.J.), Spil, W.E. (Willem) van, Wijmenga, C. (Cisca), Zwinderman, A.H. (Ailko), Zhernikova, A. (A.), Jukema, J.W. (Jan Wouter), Mei, H. (H.), Slofstra, M. (M.), Swertz, M. (M.), Akker, E.B. (Erik) van den, Deelen, J. (Joris), Reinders, M.J.T. (M. J.T.), Harms, A.C. (Amy), Hankemeier, T. (Thomas), Bartels, M. (Meike), Nivard, M. (Michel), and Boomsma, D.I. (Dorret)

Abstract

The original version of the Supplementary Information associated with this Article included an incorrect Supplementary Data 1 file, in which additional delimiters were included in the first column for a number of rows, resulting in column shifts for some of these rows. The HTML has been updated to include a corrected version of Supplementary Data 1; the original incorrect version of Supplementary Data 1 can be found as Supplementary Information associated with this Correction. In addition, the original version of this Article contained an error in the author affiliations. An affiliation of Abdel Abdellaoui with Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2020
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6. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Author

Li, C. (Chen), Stoma, S. (Svetlana), Lotta, L.A. (Luca A.), Warner, S. (Sophie), Albrecht, E. (Eva), Allione, A. (Alessandra), Arp, P.P. (Pascal), Broer, L. (Linda), Buxton, J.L. (Jessica L.), Da Silva Couto Alves, A. (Alexessander), Deelen, J. (Joris), Fedko, I.O. (Iryna O.), Gordon, S.D. (Scott D.), Jiang, T. (Tao), Karlsson, R. (Robert), Kerrison, N. (Nicola), Loe, T.K. (Taylor K.), Mangino, M. (Massimo), Milaneschi, Y. (Yuri), Miraglio, B. (Benjamin), Pervjakova, N. (Natalia), Russo, A. (Alessia), Surakka, I. (Ida), Spek, A. (Ashley) van der, Verhoeven, J.E. (Josine E.), Amin, N. (Najaf), Beekman, M. (Marian), Blakemore, A.I. (Alexandra I.), Canzian, F. (Federico), Hamby, S.E. (Stephen E.), Hottenga, J.J. (Jouke Jan), Jones, P.D. (Peter D.), Jousilahti, P. (Pekka), Mägi, R. (Reedik), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Nyholt, D.R. (Dale), Perola, M. (Markus), Pietilainen, K.H. (Kirsi Hannele), Salomaa, V. (Veikko), Sillanpää, E. (Elina), Suchiman, H.E. (H. Eka), Heemst, D. (Diana) van, Willemsen, G. (Gonneke), Agudo, A. (Antonio), Boeing, H. (Heiner), Boomsma, D.I. (Dorret), Chirlaque, M.D. (M.), Fagherazzi, G. (Guy), Ferrari, P. (Pietro), Franks, P. (Paul), Gieger, C. (Christian), Hagen, K. (Knut), Gunter, M.J. (Marc J.), Hägg, S. (Sara), Hovatta, I. (Iiris), Imaz, L. (Liher), Kaprio, J. (Jaakko), Kaaks, R. (Rudolf), Key, T. (Tim), Krogh, V. (Vittorio), Martin, N.G. (Nicholas), Melander, O. (Olle), Metspalu, A. (Andres), Moreno, C. (Concha), Onland-Moret, N.C. (N. Charlotte), Nilsson, P. (Peter), Ong, K.K. (Ken K.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Quirós, J.R., Jarvelin, M.R. (Marjo Riitta), Rodríguez-Barranco, M. (Miguel), Scott, R.A. (Robert A.), Severi, G. (Gianluca), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Tjønneland, A. (Anne), Trichopoulou, A. (Antonia), Tumino, R. (Rosario), Uitterlinden, A.G. (André G.), Schouw, Y.T. (Yvonne) van der, Duijn, C.M. (Cornelia) van, Weiderpass, E. (Elisabete), Denchi, E.L. (Eros Lazzerini), Matullo, G., Butterworth, A.S. (Adam S.), Danesh, J. (John), Samani, N.J. (Nilesh), Wareham, N.J. (Nick), Nelson, C.P. (Christopher P.), Langenberg, C. (Claudia), Codd, V. (Veryan), Li, C. (Chen), Stoma, S. (Svetlana), Lotta, L.A. (Luca A.), Warner, S. (Sophie), Albrecht, E. (Eva), Allione, A. (Alessandra), Arp, P.P. (Pascal), Broer, L. (Linda), Buxton, J.L. (Jessica L.), Da Silva Couto Alves, A. (Alexessander), Deelen, J. (Joris), Fedko, I.O. (Iryna O.), Gordon, S.D. (Scott D.), Jiang, T. (Tao), Karlsson, R. (Robert), Kerrison, N. (Nicola), Loe, T.K. (Taylor K.), Mangino, M. (Massimo), Milaneschi, Y. (Yuri), Miraglio, B. (Benjamin), Pervjakova, N. (Natalia), Russo, A. (Alessia), Surakka, I. (Ida), Spek, A. (Ashley) van der, Verhoeven, J.E. (Josine E.), Amin, N. (Najaf), Beekman, M. (Marian), Blakemore, A.I. (Alexandra I.), Canzian, F. (Federico), Hamby, S.E. (Stephen E.), Hottenga, J.J. (Jouke Jan), Jones, P.D. (Peter D.), Jousilahti, P. (Pekka), Mägi, R. (Reedik), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Nyholt, D.R. (Dale), Perola, M. (Markus), Pietilainen, K.H. (Kirsi Hannele), Salomaa, V. (Veikko), Sillanpää, E. (Elina), Suchiman, H.E. (H. Eka), Heemst, D. (Diana) van, Willemsen, G. (Gonneke), Agudo, A. (Antonio), Boeing, H. (Heiner), Boomsma, D.I. (Dorret), Chirlaque, M.D. (M.), Fagherazzi, G. (Guy), Ferrari, P. (Pietro), Franks, P. (Paul), Gieger, C. (Christian), Hagen, K. (Knut), Gunter, M.J. (Marc J.), Hägg, S. (Sara), Hovatta, I. (Iiris), Imaz, L. (Liher), Kaprio, J. (Jaakko), Kaaks, R. (Rudolf), Key, T. (Tim), Krogh, V. (Vittorio), Martin, N.G. (Nicholas), Melander, O. (Olle), Metspalu, A. (Andres), Moreno, C. (Concha), Onland-Moret, N.C. (N. Charlotte), Nilsson, P. (Peter), Ong, K.K. (Ken K.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Quirós, J.R., Jarvelin, M.R. (Marjo Riitta), Rodríguez-Barranco, M. (Miguel), Scott, R.A. (Robert A.), Severi, G. (Gianluca), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Tjønneland, A. (Anne), Trichopoulou, A. (Antonia), Tumino, R. (Rosario), Uitterlinden, A.G. (André G.), Schouw, Y.T. (Yvonne) van der, Duijn, C.M. (Cornelia) van, Weiderpass, E. (Elisabete), Denchi, E.L. (Eros Lazzerini), Matullo, G., Butterworth, A.S. (Adam S.), Danesh, J. (John), Samani, N.J. (Nilesh), Wareham, N.J. (Nick), Nelson, C.P. (Christopher P.), Langenberg, C. (Claudia), and Codd, V. (Veryan)

Abstract

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.

Published
2020
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7. Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Author

Hagenbeek, F.A. (Fiona A.), Pool, R. (Reńe), Dongen, J. (Jenny) van, Draisma, G. (Gerrit), Hottenga, J.J. (Jouke Jan), Willemsen, G. (Gonneke), Abdellaoui, A. (Abdel), Fedko, I.O. (Iryna O.), Braber, A. (Anouk) den, Visser, P.J. (Pieter Jelle), de Geus, E.J.C.N. (Eco J. C. N.), Willems van Dijk, K. (Ko), Verhoeven, A. (Aswin), Suchiman, H.E. (H. Eka), Beekman, M. (Marian), Slagboom, P.E. (Eline), Duijn, C.M. (Cornelia) van, Barkey Wolf, J.J.H. (J. J.H.), Cats, D. (D.), Amin, N. (N.), Beulens, J.W.J. (Joline), van der Bom, J.A. (J. A.), Bomer, N. (Nils), Demirkan, A. (Ayşe), van Hilten, J.A. (J. A.), Meessen, J.M.T.A. (J. M.T.A.), Moed, H. (Heleen), Fu, J. (J.), Onderwater, G.L.J. (G. L.J.), Rutters, F. (F.), So-Osman, C. (Cynthia), Flier, W.M. (Wiesje) van der, Heijden, A.A.W.A. (Amber A. W.) van der, Spek, A. (Ashley) van der, Asselbergs, F.W. (F. W.), Boersma, H. (Eric), Elders, P.M. (P. M.), Geleijnse, J.M. (Marianne), Ikram, M.A. (Arfan), Kloppenburg, M. (Margreet), Meulenbelt, I. (I.), Mooijaart, S.P. (Simon), Nelissen, R.G.H.H. (Rob), Netea, M.G. (Mihai), Penninx, B.W.J.H. (Brenda), Stehouwer, C.D. (Coen), Teunissen, C.E. (Charlotte), Terwindt, G.M. (Gisela), ‘t Hart, L.M. (L. M.), Maagdenberg, A.M.J.M. (Arn), Harst, P. (Pim) van der, van der Horst, I.C.C. (I. C.C.), Kallen, C.J. van der, van Greevenbroek, M.M.J. (M. M.J.), Spil, W.E. (Willem) van, Wijmenga, C. (C.), Zwinderman, A.H. (A. H.), Zhernikova, A. (A.), Jukema, J.W. (Jan Wouter), Mei, H. (H.), Slofstra, M. (M.), Swertz, M. (M.), Akker, E.B. (Erik) van den, Deelen, J. (Joris), Reinders, M.J.T. (M. J.T.), Harms, A.C. (Amy C.), Hankemeier, T. (Thomas), Bartels, M. (Meike), Nivard, M. (Michel), Boomsma, D.I. (Dorret), Hagenbeek, F.A. (Fiona A.), Pool, R. (Reńe), Dongen, J. (Jenny) van, Draisma, G. (Gerrit), Hottenga, J.J. (Jouke Jan), Willemsen, G. (Gonneke), Abdellaoui, A. (Abdel), Fedko, I.O. (Iryna O.), Braber, A. (Anouk) den, Visser, P.J. (Pieter Jelle), de Geus, E.J.C.N. (Eco J. C. N.), Willems van Dijk, K. (Ko), Verhoeven, A. (Aswin), Suchiman, H.E. (H. Eka), Beekman, M. (Marian), Slagboom, P.E. (Eline), Duijn, C.M. (Cornelia) van, Barkey Wolf, J.J.H. (J. J.H.), Cats, D. (D.), Amin, N. (N.), Beulens, J.W.J. (Joline), van der Bom, J.A. (J. A.), Bomer, N. (Nils), Demirkan, A. (Ayşe), van Hilten, J.A. (J. A.), Meessen, J.M.T.A. (J. M.T.A.), Moed, H. (Heleen), Fu, J. (J.), Onderwater, G.L.J. (G. L.J.), Rutters, F. (F.), So-Osman, C. (Cynthia), Flier, W.M. (Wiesje) van der, Heijden, A.A.W.A. (Amber A. W.) van der, Spek, A. (Ashley) van der, Asselbergs, F.W. (F. W.), Boersma, H. (Eric), Elders, P.M. (P. M.), Geleijnse, J.M. (Marianne), Ikram, M.A. (Arfan), Kloppenburg, M. (Margreet), Meulenbelt, I. (I.), Mooijaart, S.P. (Simon), Nelissen, R.G.H.H. (Rob), Netea, M.G. (Mihai), Penninx, B.W.J.H. (Brenda), Stehouwer, C.D. (Coen), Teunissen, C.E. (Charlotte), Terwindt, G.M. (Gisela), ‘t Hart, L.M. (L. M.), Maagdenberg, A.M.J.M. (Arn), Harst, P. (Pim) van der, van der Horst, I.C.C. (I. C.C.), Kallen, C.J. van der, van Greevenbroek, M.M.J. (M. M.J.), Spil, W.E. (Willem) van, Wijmenga, C. (C.), Zwinderman, A.H. (A. H.), Zhernikova, A. (A.), Jukema, J.W. (Jan Wouter), Mei, H. (H.), Slofstra, M. (M.), Swertz, M. (M.), Akker, E.B. (Erik) van den, Deelen, J. (Joris), Reinders, M.J.T. (M. J.T.), Harms, A.C. (Amy C.), Hankemeier, T. (Thomas), Bartels, M. (Meike), Nivard, M. (Michel), and Boomsma, D.I. (Dorret)

Abstract

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 5

Published
2020
Full Text
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8. Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Author

Hagenbeek, Fiona A., Pool, René, van Dongen, Jenny, Draisma, Harmen H.M., Hottenga, Jouke Jan, Willemsen, Gonneke, Abdellaoui, Abdel, Fedko, Iryna O., den Braber, Anouk, Visser, Pieter Jelle, de Geus, Eco J.C.N., Willems van Dijk, Ko, Verhoeven, Aswin, Suchiman, H.E., Beekman, Marian, Slagboom, Eline P., van Duijn, Cornelia M., Barkey Wolf, J.J.H., Cats, D., Amin, N., Beulens, J.W., van der Bom, J.A., Bomer, N., Demirkan, A., van Hilten, J.A., Meessen, J.M.T.A., Moed, M.H., Fu, J., Onderwater, G.L.J., Rutters, F., So-Osman, C., van der Flier, W.M., van der Heijden, A.A.W.A., van der Spek, A., Asselbergs, F.W., Boersma, E., Elders, P.M., Geleijnse, J.M., Ikram, M.A., Kloppenburg, M., Meulenbelt, I., Mooijaart, S.P., Nelissen, R.G.H.H., Netea, M.G., Penninx, B.W.J.H., Stehouwer, C.D.A., Teunissen, C.E., Terwindt, G.M., Jukema, J.W., Reinders, M.J.T., Hagenbeek, Fiona A., Pool, René, van Dongen, Jenny, Draisma, Harmen H.M., Hottenga, Jouke Jan, Willemsen, Gonneke, Abdellaoui, Abdel, Fedko, Iryna O., den Braber, Anouk, Visser, Pieter Jelle, de Geus, Eco J.C.N., Willems van Dijk, Ko, Verhoeven, Aswin, Suchiman, H.E., Beekman, Marian, Slagboom, Eline P., van Duijn, Cornelia M., Barkey Wolf, J.J.H., Cats, D., Amin, N., Beulens, J.W., van der Bom, J.A., Bomer, N., Demirkan, A., van Hilten, J.A., Meessen, J.M.T.A., Moed, M.H., Fu, J., Onderwater, G.L.J., Rutters, F., So-Osman, C., van der Flier, W.M., van der Heijden, A.A.W.A., van der Spek, A., Asselbergs, F.W., Boersma, E., Elders, P.M., Geleijnse, J.M., Ikram, M.A., Kloppenburg, M., Meulenbelt, I., Mooijaart, S.P., Nelissen, R.G.H.H., Netea, M.G., Penninx, B.W.J.H., Stehouwer, C.D.A., Teunissen, C.E., Terwindt, G.M., Jukema, J.W., and Reinders, M.J.T.

Abstract

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2 Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.

Published
2020

9. Unraveling the role of WWP2 in osteoarthritis pathophysiology

Author

Tuerlings, M., primary, Houtman, E., additional, van Hoolwerff, M., additional, Coutinho de Almeida, R., additional, Ruiz, A. Rodriguez, additional, Lakenberg, N., additional, Suchiman, H.E., additional, Timmermans, R.G., additional, Ramos, Y.F., additional, and Meulenbelt, I., additional

Published
2019
Full Text
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11. Whole-genome sequence variation, population structure and demographic history of the Dutch population

Author

Francioli, L.C., Menelaou, A., Pulit, S.L., Dijk, F. van, Palamara, P.F., Elbers, C.C., Neerincx, P.B., Ye, K., Guryev, V., Kloosterman, W.P., Deelen, P., Abdellaoui, A., Leeuwen, E.M. van, Oven, M. van, Vermaat, M., Li, M., Laros, J.F., Karssen, L.C., Kanterakis, A., Amin, N., Hottenga, J.J., Lameijer, E.W., Kattenberg, M., Dijkstra, M., Byelas, H., Setten, J. van, Schaik, B.D. van, Bot, J., Nijman, I.J., Renkens, I., Marschall, T., Schönhuth, A., Hehir-Kwa, J.Y., Handsaker, R.E., Polak, P., Sohail, M., Vuzman, D., Hormozdiari, F., Enckevort, D. van, Mei, H., Koval, V., Moed, M.H., Velde, K.J. van der, Rivadeneira, F., Estrada, K., Medina-Gomez, C., Isaacs, A., McCarroll, S.A., Beekman, M., Craen, A.J. de, Suchiman, H.E., Hofman, A., Oostra, B., Uitterlinden, A.G., Willemsen, G., Platteel, M., Veldink, J.H., Berg, L.H. van den, Pitts, S.J., Potluri, S., Sundar, P., Cox, D.R., Sunyaev, S.R., Dunnen, J.T. den, Stoneking, M., Knijff, P. de, Kayser, M., Li, Q., Li, Y., Du, Y., Chen, R., Cao, H., Li, N., Cao, S., Wang, J, Bovenberg, J.A., Pe'er, I., Slagboom, P.E., Duijn, C.M. van, Boomsma, D.I., Ommen, G.J. van, Bakker, P.I. de, Swertz, M.A., Wijmenga, C., Francioli, L.C., Menelaou, A., Pulit, S.L., Dijk, F. van, Palamara, P.F., Elbers, C.C., Neerincx, P.B., Ye, K., Guryev, V., Kloosterman, W.P., Deelen, P., Abdellaoui, A., Leeuwen, E.M. van, Oven, M. van, Vermaat, M., Li, M., Laros, J.F., Karssen, L.C., Kanterakis, A., Amin, N., Hottenga, J.J., Lameijer, E.W., Kattenberg, M., Dijkstra, M., Byelas, H., Setten, J. van, Schaik, B.D. van, Bot, J., Nijman, I.J., Renkens, I., Marschall, T., Schönhuth, A., Hehir-Kwa, J.Y., Handsaker, R.E., Polak, P., Sohail, M., Vuzman, D., Hormozdiari, F., Enckevort, D. van, Mei, H., Koval, V., Moed, M.H., Velde, K.J. van der, Rivadeneira, F., Estrada, K., Medina-Gomez, C., Isaacs, A., McCarroll, S.A., Beekman, M., Craen, A.J. de, Suchiman, H.E., Hofman, A., Oostra, B., Uitterlinden, A.G., Willemsen, G., Platteel, M., Veldink, J.H., Berg, L.H. van den, Pitts, S.J., Potluri, S., Sundar, P., Cox, D.R., Sunyaev, S.R., Dunnen, J.T. den, Stoneking, M., Knijff, P. de, Kayser, M., Li, Q., Li, Y., Du, Y., Chen, R., Cao, H., Li, N., Cao, S., Wang, J, Bovenberg, J.A., Pe'er, I., Slagboom, P.E., Duijn, C.M. van, Boomsma, D.I., Ommen, G.J. van, Bakker, P.I. de, Swertz, M.A., and Wijmenga, C.

Abstract

Contains fulltext : 137213.pdf (publisher's version ) (Closed access), Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage ( approximately 13x) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies.

Published
2014

12. Identification and systematic annotation of tissue-specific differentially methylated regions using the Illumina 450k array

Author

Slieker, R.C., Bos, S.D., Goeman, J.J., Bovee, J.V., Talens, R.P., Breggen, R. van der, Suchiman, H.E., Lameijer, E.W., Putter, H., Akker, E.B. van den, Zhang, Y., Jukema, J.W., Slagboom, P.E., Meulenbelt, I., Heijmans, B.T., Slieker, R.C., Bos, S.D., Goeman, J.J., Bovee, J.V., Talens, R.P., Breggen, R. van der, Suchiman, H.E., Lameijer, E.W., Putter, H., Akker, E.B. van den, Zhang, Y., Jukema, J.W., Slagboom, P.E., Meulenbelt, I., and Heijmans, B.T.

Abstract

Contains fulltext : 125872.pdf (publisher's version ) (Open Access), BACKGROUND: DNA methylation has been recognized as a key mechanism in cell differentiation. Various studies have compared tissues to characterize epigenetically regulated genomic regions, but due to differences in study design and focus there still is no consensus as to the annotation of genomic regions predominantly involved in tissue-specific methylation. We used a new algorithm to identify and annotate tissue-specific differentially methylated regions (tDMRs) from Illumina 450k chip data for four peripheral tissues (blood, saliva, buccal swabs and hair follicles) and six internal tissues (liver, muscle, pancreas, subcutaneous fat, omentum and spleen with matched blood samples). RESULTS: The majority of tDMRs, in both relative and absolute terms, occurred in CpG-poor regions. Further analysis revealed that these regions were associated with alternative transcription events (alternative first exons, mutually exclusive exons and cassette exons). Only a minority of tDMRs mapped to gene-body CpG islands (13%) or CpG islands shores (25%) suggesting a less prominent role for these regions than indicated previously. Implementation of ENCODE annotations showed enrichment of tDMRs in DNase hypersensitive sites and transcription factor binding sites. Despite the predominance of tissue differences, inter-individual differences in DNA methylation in internal tissues were correlated with those for blood for a subset of CpG sites in a locus- and tissue-specific manner. CONCLUSIONS: We conclude that tDMRs preferentially occur in CpG-poor regions and are associated with alternative transcription. Furthermore, our data suggest the utility of creating an atlas cataloguing variably methylated regions in internal tissues that correlate to DNA methylation measured in easy accessible peripheral tissues.

Published
2013

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