Genotype/fenotype database voor gedragsgenetisch en genetisch epidemiologisch onderzoek
Projectomschrijving
Depressie en hart- en vaatziekten komen vaak samen voor. Beide ziekten worden gekenmerkt door afwijkende waardes in stoffen in het bloed die deel uitmaken van het immuunsysteem. Erfelijke factoren bepalen voor een belangrijk deel de nivo’s van deze bloedfactoren, die mogelijk als biomarkers voor het dubbele risico op deze aandoeningen gebruikt kunnen worden. Met behulp van de ZonMW subsidie worden bepalingen van deze biomarkers verricht bij 9500 deelnemers aan het Nederlandse Tweelingenregister van de Vrije Universiteit. Daarmee kunnen de relaties tussen erfelijke aanleg, het immuunsysteem, depressie en hart- en vaatziekten beter worden onderzocht.
Producten
Titel: A 3p26-3p25 genetic linkage finding for DSM-IV major depression in heavy smoking families.
Auteur: Pergadia ML, Glowinski AL, Wray NR, Agrawal A, Saccone SF, Loukola A, Broms U, Korhonen T, Penninx BW, Grant JD, Nelson EC, Henders AK, Schrage AJ, Chou YL, Keskitalo-Vuokko K, Zhu Q, Gordon SD, Vink JM, de Geus EJ, Macgregor S, Liu JZ, Willemsen G, Medland SE, Boomsma DI, Montgomery GW, Rice JP, Goate AM, Heath AC, Kaprio J, Martin NG, Madden PA
Magazine: American Journal of Psychiatry
Auteur: Pergadia ML, Glowinski AL, Wray NR, Agrawal A, Saccone SF, Loukola A, Broms U, Korhonen T, Penninx BW, Grant JD, Nelson EC, Henders AK, Schrage AJ, Chou YL, Keskitalo-Vuokko K, Zhu Q, Gordon SD, Vink JM, de Geus EJ, Macgregor S, Liu JZ, Willemsen G, Medland SE, Boomsma DI, Montgomery GW, Rice JP, Goate AM, Heath AC, Kaprio J, Martin NG, Madden PA
Magazine: American Journal of Psychiatry
Titel: LPAR1 and ITGA4 regulate peripheral blood monocyte counts.
Auteur: Maugeri N, Powell J, 't Hoen PA, de Geus EJ, Willemsen G, Kattenberg M, Henders AK, Wallace L, Penninx B, Hottenga JJ, Medland SE, Saviouk V, Martin NG, Visscher PM, van Ommen GJ, Frazer IH, Boomsma DI, Montgomery GW, Ferreira MA.
Magazine: Human Mutation
Auteur: Maugeri N, Powell J, 't Hoen PA, de Geus EJ, Willemsen G, Kattenberg M, Henders AK, Wallace L, Penninx B, Hottenga JJ, Medland SE, Saviouk V, Martin NG, Visscher PM, van Ommen GJ, Frazer IH, Boomsma DI, Montgomery GW, Ferreira MA.
Magazine: Human Mutation
Titel: Meta-analysis of genome-wide association
for migraine in six population-based European cohorts.
Auteur: Ligthart L, de Vries B, Smith AV, Ikram MA, Amin N, Hottenga JJ, Koelewijn SC, Kattenberg VM, de Moor MH, Janssens AC, Aulchenko YS, Oostra BA, de Geus EJ, Smit JH, Zitman FG, Uitterlinden AG, Hofman A, Willemsen G, Nyholt DR, Montgomery GW, Terwindt GM, Gudnason V, Penninx BW, Breteler M, Ferrari MD, Launer LJ, van Duijn CM, van den Maagdenberg AM, Boomsma DI.
Magazine: European Journal of Human Genetics
Auteur: Ligthart L, de Vries B, Smith AV, Ikram MA, Amin N, Hottenga JJ, Koelewijn SC, Kattenberg VM, de Moor MH, Janssens AC, Aulchenko YS, Oostra BA, de Geus EJ, Smit JH, Zitman FG, Uitterlinden AG, Hofman A, Willemsen G, Nyholt DR, Montgomery GW, Terwindt GM, Gudnason V, Penninx BW, Breteler M, Ferrari MD, Launer LJ, van Duijn CM, van den Maagdenberg AM, Boomsma DI.
Magazine: European Journal of Human Genetics
Titel: New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism
Auteur: Horikoshi M et al
Magazine: Nature Genetics
Auteur: Horikoshi M et al
Magazine: Nature Genetics
Titel: Population structure, migration, and diversifying selection in the Netherlands
Auteur: Abdellaoui A, Hottenga JJ, Knijff PD, Nivard MG, Xiao X, Scheet P, Brooks A, Ehli EA, Hu Y, Davies GE, Hudziak JJ, Sullivan PF, van Beijsterveldt T, Willemsen G, de Geus EJ, Penninx BW, Boomsma DI1
Magazine: European Journal of Human Genetics
Auteur: Abdellaoui A, Hottenga JJ, Knijff PD, Nivard MG, Xiao X, Scheet P, Brooks A, Ehli EA, Hu Y, Davies GE, Hudziak JJ, Sullivan PF, van Beijsterveldt T, Willemsen G, de Geus EJ, Penninx BW, Boomsma DI1
Magazine: European Journal of Human Genetics
Titel: The molecular genetic architecture of self-employment
Auteur: Van der Loos MJ, Rietveld CA, Eklund N, Koellinger PD, Rivadeneira F, Abecasis GR, Ankra-Badu GA, Baumeister SE, Benjamin DJ, Biffar R, Blankenberg S, Boomsma DI, Cesarini D, Cucca F, de Geus EJ, Dedoussis G, Deloukas P, Dimitriou M, Eiriksdottir G, Eriksson J, Gieger C, Gudnason V, Höhne B, Holle R, Hottenga JJ, Isaacs A, Järvelin MR, Johannesson M, Kaakinen M, Kähönen M, Kanoni S, Laaksonen MA, Lahti J, Launer LJ, Lehtimäki T, Loitfelder M, Magnusson PK, Naitza S, Oostra BA, Perola M, Pet
Magazine: PLoS ONE
Auteur: Van der Loos MJ, Rietveld CA, Eklund N, Koellinger PD, Rivadeneira F, Abecasis GR, Ankra-Badu GA, Baumeister SE, Benjamin DJ, Biffar R, Blankenberg S, Boomsma DI, Cesarini D, Cucca F, de Geus EJ, Dedoussis G, Deloukas P, Dimitriou M, Eiriksdottir G, Eriksson J, Gieger C, Gudnason V, Höhne B, Holle R, Hottenga JJ, Isaacs A, Järvelin MR, Johannesson M, Kaakinen M, Kähönen M, Kanoni S, Laaksonen MA, Lahti J, Launer LJ, Lehtimäki T, Loitfelder M, Magnusson PK, Naitza S, Oostra BA, Perola M, Pet
Magazine: PLoS ONE
Titel: The heritability of metabolic syndrome traits in a large population-based sample
Auteur: van Dongen J, Willemsen G, Chen WM, de Geus EJ, Boomsma DI
Magazine: Journal of Lipid Research
Auteur: van Dongen J, Willemsen G, Chen WM, de Geus EJ, Boomsma DI
Magazine: Journal of Lipid Research
Titel: A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
Auteur: Manning et al.
Magazine: Nature Genetics
Auteur: Manning et al.
Magazine: Nature Genetics
Titel: The adult Netherlands twin register: twenty-five years of survey and biological data collection
Auteur: Willemsen G, Vink JM, Abdellaoui A, den Braber A, van Beek JH, Draisma HH, van Dongen J, van 't Ent D, Geels LM, van Lien R, Ligthart L, Kattenberg M, Mbarek H, de Moor MH, Neijts M, Pool R, Stroo N, Kluft C, Suchiman HE, Slagboom PE, de Geus EJ, Boomsma DI
Magazine: Twin Research and Human Genetics
Auteur: Willemsen G, Vink JM, Abdellaoui A, den Braber A, van Beek JH, Draisma HH, van Dongen J, van 't Ent D, Geels LM, van Lien R, Ligthart L, Kattenberg M, Mbarek H, de Moor MH, Neijts M, Pool R, Stroo N, Kluft C, Suchiman HE, Slagboom PE, de Geus EJ, Boomsma DI
Magazine: Twin Research and Human Genetics
Titel: A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol
Auteur: Surakka I, Whitfield JB, Perola M, Visscher PM, Montgomery GW, Falchi M, Willemsen G, de Geus EJ, Magnusson PK, Christensen K, Sørensen TI, Pietiläinen KH, Rantanen T, Silander K, Widén E, Muilu J, Rahman I, Liljedahl U, Syvänen AC, Palotie A, Kaprio J, Kyvik KO, Pedersen NL, Boomsma DI, Spector T, Martin NG, Ripatti S, Peltonen L
Magazine: Twin Research and Human Genetics
Auteur: Surakka I, Whitfield JB, Perola M, Visscher PM, Montgomery GW, Falchi M, Willemsen G, de Geus EJ, Magnusson PK, Christensen K, Sørensen TI, Pietiläinen KH, Rantanen T, Silander K, Widén E, Muilu J, Rahman I, Liljedahl U, Syvänen AC, Palotie A, Kaprio J, Kyvik KO, Pedersen NL, Boomsma DI, Spector T, Martin NG, Ripatti S, Peltonen L
Magazine: Twin Research and Human Genetics
Titel: Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
Auteur: den Hoed M et al
Magazine: Nature Genetics
Auteur: den Hoed M et al
Magazine: Nature Genetics
Titel: Seventy-five genetic loci influencing the human red blood cell
Auteur: van der Harst P et al
Magazine: Nature
Auteur: van der Harst P et al
Magazine: Nature
Titel: Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
Auteur: Scott et al.
Magazine: Nature Genetics
Auteur: Scott et al.
Magazine: Nature Genetics
Titel: A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.
Auteur: Surakka I, Isaacs A, Karssen LC, Laurila PP, Middelberg RP, Tikkanen E, Ried JS, Lamina C, Mangino M, Igl W, Hottenga JJ, Lagou V, van der Harst P, Mateo Leach I, Esko T, Kutalik Z, Wainwright NW, Struchalin MV, Sarin AP, Kangas AJ, Viikari JS, Perola M, Rantanen T, Petersen AK, Soininen P, Johansson A, Soranzo N, Heath AC, Papamarkou T, Prokopenko I, Tönjes A, Kronenberg F, Döring A, Rivadeneira F, Montgomery GW, Whitfield JB, Kähönen M, Lehtimäki T, Freimer NB, Willemsen G, de Geus EJ, Pa
Magazine: PLoS Genetics
Auteur: Surakka I, Isaacs A, Karssen LC, Laurila PP, Middelberg RP, Tikkanen E, Ried JS, Lamina C, Mangino M, Igl W, Hottenga JJ, Lagou V, van der Harst P, Mateo Leach I, Esko T, Kutalik Z, Wainwright NW, Struchalin MV, Sarin AP, Kangas AJ, Viikari JS, Perola M, Rantanen T, Petersen AK, Soininen P, Johansson A, Soranzo N, Heath AC, Papamarkou T, Prokopenko I, Tönjes A, Kronenberg F, Döring A, Rivadeneira F, Montgomery GW, Whitfield JB, Kähönen M, Lehtimäki T, Freimer NB, Willemsen G, de Geus EJ, Pa
Magazine: PLoS Genetics
Titel: Genome-wide meta-analysis of common variant differences between men and women
Auteur: Boraska et al.
Magazine: Human Molecular Genetics
Auteur: Boraska et al.
Magazine: Human Molecular Genetics
Titel: Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
Auteur: Stolk et al.
Magazine: Nature Genetics
Auteur: Stolk et al.
Magazine: Nature Genetics
Titel: Genetic Architecture of the Pro-Inflammatory State in an Extended Twin-Family Design
Auteur: Neijts M, van Dongen J, Kluft C, Boomsma DI, Willemsen G, de Geus EJ
Magazine: Twin Research and Human Genetics
Auteur: Neijts M, van Dongen J, Kluft C, Boomsma DI, Willemsen G, de Geus EJ
Magazine: Twin Research and Human Genetics
Titel: Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
Auteur: Chambers JC et al.
Magazine: Nature Genetics
Auteur: Chambers JC et al.
Magazine: Nature Genetics
Titel: Genome-wide analyses of borderline personality features
Auteur: Lubke GH, Laurin C, Amin N, Hottenga JJ, Willemsen G, van Grootheest G, Abdellaoui A, Karssen LC, Oostra BA, van Duijn CM, Penninx BW, Boomsma DI
Magazine: Molecular Psychiatry
Auteur: Lubke GH, Laurin C, Amin N, Hottenga JJ, Willemsen G, van Grootheest G, Abdellaoui A, Karssen LC, Oostra BA, van Duijn CM, Penninx BW, Boomsma DI
Magazine: Molecular Psychiatry
Titel: Loci affecting gamma-glutamyl transferase in adults and adolescents show age x snp interaction and cardiometabolic disease associations.
Auteur: Middelberg RP, Benyamin B, de Moor MH, Warrington NM, Gordon S, Henders AK, Medland SE, Nyholt DR, de Geus EJ, Hottenga JJ, Willemsen G, Beilin LJ, Mori TA, Wright MJ, Heath AC, Madden PA, Boomsma DI, Pennell CE, Montgomery GW, Martin NG, Whitfield JB.
Magazine: Human Molecular Genetics
Auteur: Middelberg RP, Benyamin B, de Moor MH, Warrington NM, Gordon S, Henders AK, Medland SE, Nyholt DR, de Geus EJ, Hottenga JJ, Willemsen G, Beilin LJ, Mori TA, Wright MJ, Heath AC, Madden PA, Boomsma DI, Pennell CE, Montgomery GW, Martin NG, Whitfield JB.
Magazine: Human Molecular Genetics
Titel: The Use of Imputed Sibling Genotypes in Sibship-Based Association Analysis: On Modeling Alternatives, Power and Model Misspecification
Auteur: Minică CC, Dolan CV, Hottenga JJ, Willemsen G, Vink JM, Boomsma DI
Magazine: Behavior Genetics
Auteur: Minică CC, Dolan CV, Hottenga JJ, Willemsen G, Vink JM, Boomsma DI
Magazine: Behavior Genetics
Titel: Identification of common variants associated with human hippocampal and intracranial volumes
Auteur: Stein et al for the Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium
Magazine: Nature Genetics
Auteur: Stein et al for the Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium
Magazine: Nature Genetics
Titel: Meta-analysis of genome-wide association studies in >80000 subjects identifies multiple loci for C-reactive protein levels.
Auteur: Dehghan A et al.
Magazine: Circulation
Auteur: Dehghan A et al.
Magazine: Circulation
Titel: Identification of IL6R and chromosome 11q13.5 as risk loci for asthma
Auteur: Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souëf P, Danoy P, Baltic S, Nyholt DR, Jenkins M, Hayden C, Willemsen G, Ang W, Kuokkanen M, Beilby J, Cheah F, de Geus EJ, Ramasamy A, Vedantam S, Salomaa V, Madden PA, Heath AC, Hopper JL, Visscher PM, Musk B, Leeder SR, Jarvelin MR, Pennell C, Boomsma DI, Hirschhorn JN, Walters H, Martin NG, James A, Jones G, Abramson MJ, Robertson CF, Dharmage SC, Brown MA, Montgomery GW, Thompson PJ; Australian Asthma Genetics Consortium
Magazine: Lancet
Auteur: Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souëf P, Danoy P, Baltic S, Nyholt DR, Jenkins M, Hayden C, Willemsen G, Ang W, Kuokkanen M, Beilby J, Cheah F, de Geus EJ, Ramasamy A, Vedantam S, Salomaa V, Madden PA, Heath AC, Hopper JL, Visscher PM, Musk B, Leeder SR, Jarvelin MR, Pennell C, Boomsma DI, Hirschhorn JN, Walters H, Martin NG, James A, Jones G, Abramson MJ, Robertson CF, Dharmage SC, Brown MA, Montgomery GW, Thompson PJ; Australian Asthma Genetics Consortium
Magazine: Lancet
Titel: Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
Auteur: Wain LV et al.
Magazine: Nature Genetics
Auteur: Wain LV et al.
Magazine: Nature Genetics
Titel: The Netherlands Twin Register Biobank; a resource for genetic epidemiological studies.
Auteur: Willemsen G, EJC de Geus, Bartels M, Beijsterveldt CEMT van, Brooks AI, Estourgie-van Burk GF, Fugman DA, Hoekstra C, Hottenga JJ, Kluft K, Meijer P, Montgomery GW, Rizzu P, Sondervan D, Smit AB, Spijker S, Suchiman HED, Tischfield JA, Lehner T, Slagboom PE, Boomsma DI.
Magazine: Twin Research and Human Genetics
Auteur: Willemsen G, EJC de Geus, Bartels M, Beijsterveldt CEMT van, Brooks AI, Estourgie-van Burk GF, Fugman DA, Hoekstra C, Hottenga JJ, Kluft K, Meijer P, Montgomery GW, Rizzu P, Sondervan D, Smit AB, Spijker S, Suchiman HED, Tischfield JA, Lehner T, Slagboom PE, Boomsma DI.
Magazine: Twin Research and Human Genetics
Titel: New gene functions in megakaryopoiesis and platelet formation
Auteur: Gieger C et al
Magazine: Nature
Auteur: Gieger C et al
Magazine: Nature
Titel: The role of adiposity in cardiometabolic traits: a mendelian randomization analysis
Auteur: Fall T et al
Magazine: PLoS Medicine
Auteur: Fall T et al
Magazine: PLoS Medicine
Titel: Identification of seven loci affecting mean telomere length and their association with disease
Auteur: Codd V et al
Magazine: Nature Genetics
Auteur: Codd V et al
Magazine: Nature Genetics
Titel: Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease
Auteur: Sabater-Lleal M et al
Magazine: Circulation
Auteur: Sabater-Lleal M et al
Magazine: Circulation
Titel: Sex differences in genetic architecture of complex phenotypes?
Auteur: Vink JM, Bartels M, van Beijsterveldt TC, van Dongen J, van Beek JH, Distel MA, de Moor MH, Smit DJ, Minica CC, Ligthart L, Geels LM, Abdellaoui A, Middeldorp CM, Hottenga JJ, Willemsen G, de Geus EJ, Boomsma DI
Magazine: PLoS ONE
Auteur: Vink JM, Bartels M, van Beijsterveldt TC, van Dongen J, van Beek JH, Distel MA, de Moor MH, Smit DJ, Minica CC, Ligthart L, Geels LM, Abdellaoui A, Middeldorp CM, Hottenga JJ, Willemsen G, de Geus EJ, Boomsma DI
Magazine: PLoS ONE
Titel: Meta-analysis of telomere length in 19713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect
Auteur: Broer L, Codd V, Nyholt DR, Deelen J, Mangino M, Willemsen G, Albrecht E, Amin N, Beekman M, de Geus EJ, Henders A, Nelson CP, Steves CJ, Wright MJ, de Craen AJ, Isaacs A, Matthews M, Moayyeri A, Montgomery GW, Oostra BA, Vink JM, Spector TD, Slagboom PE, Martin NG, Samani NJ, van Duijn CM, Boomsma DI
Magazine: European Journal of Human Genetics
Auteur: Broer L, Codd V, Nyholt DR, Deelen J, Mangino M, Willemsen G, Albrecht E, Amin N, Beekman M, de Geus EJ, Henders A, Nelson CP, Steves CJ, Wright MJ, de Craen AJ, Isaacs A, Matthews M, Moayyeri A, Montgomery GW, Oostra BA, Vink JM, Spector TD, Slagboom PE, Martin NG, Samani NJ, van Duijn CM, Boomsma DI
Magazine: European Journal of Human Genetics
Titel: Association Between Autozygosity and Major Depression Stratification Due to Religious Assortment
Auteur: Abdellaoui A, Hottenga JJ, Xiao X, Scheet P, Ehli EA, Davies GE, Hudziak JJ, Smit DJ, Bartels M, Willemsen G, Brooks A, Sullivan PF, Smit JH, de Geus EJ, Penninx BW, Boomsma DI
Magazine: Behavior Genetics
Auteur: Abdellaoui A, Hottenga JJ, Xiao X, Scheet P, Ehli EA, Davies GE, Hudziak JJ, Smit DJ, Bartels M, Willemsen G, Brooks A, Sullivan PF, Smit JH, de Geus EJ, Penninx BW, Boomsma DI
Magazine: Behavior Genetics
Titel: Depression and Heart Disease
Auteur: de Geus EJC
Auteur: de Geus EJC
Verslagen
Eindverslag
Depressie en hart- en vaatziekten komen vaak samen voor. Beide ziekten worden gekenmerkt door afwijkende waardes in stoffen in het bloed die deel uitmaken van het immuunsysteem. Met behulp van de ZonMW subsidie werden bepalingen van deze bloedfactoren verricht bij ~9000 deelnemers aan het Nederlandse Tweelingenregister van de Vrije Universiteit. De resultaten van tweelinganalyses op deze wereldwijd unieke set van gegevens laten zien dat erfelijke factoren voor een belangrijk deel de niveaux van deze bloedfactoren bepalen. Met genoombrede associatiestudies zijn nieuwe genetische varianten ontdekt die van invloed zijn op deze bloedfactoren. Daarmee kan de oorzakelijkheid van de relaties tussen het immuunsysteem en het vóórkomen depressie en hart- en vaatziekten nu beter worden.
Samenvatting van de aanvraag
Genome-wide association (GWA) studies in large samples have proven successful in identifying genetic variation underlying complex diseases and their quantitative risk factors. The Netherlands has done very well so far in GWA studies on depression and cardiovascular disease. The Netherlands Twin Registry (NTR) together with colleagues at the VUmc, LUMC, and the EUR prominently participate in two large international GWA consortia, the ESF-KP7-ENGAGE project on the metabolic syndrome (http://www.euengage.org/) and the Psychiatric GWAS Consortium on depression (https://pgc.unc.edu/pgc/index.php). To be able to take a leading role in the next level of large meta- and mega-analytic projects, we here apply for investment in the Netherlands Twin Register to become one of the leading phenotype/genotype databases in the genetic epidemiology of depression and cardiovascular disease.
The NTR has collected biological samples (mRNA, DNA, serum, plasma, urine) in >9000 participants. The resulting NTR biobank has two unique advantages over many other biobanks: sample collection is done in twin families, and genetic materials can be linked to an existing longitudinal database on mental (anxiety and depression) and physical (metabolic syndrome) health parameters and behavioral risk-modifiers (stress exposure, exercise behavior) that have been collected since 1991. As a next step, we wish to perform large-scale phenotyping of the participants on a set of inflammatory biomarkers (Tumor Necrosis Factor alpha, TNFα; Interleukin-6, IL-6; the soluble IL-6 receptor, IL-6R; C-reactive protein, CRP, and fibrinogen). The genetic factors underlying variation in these biomarkers are expected to influence the risk for depression as well as cardiovascular disease and they may explain why many patients are co-morbid for these afflictions. The investment will yield the largest genetically informative database on these biomarkers worldwide. This will allow us to:
1) successfully respond to competitive grant calls from the major genotyping facilities operated by the National Institutes of Health (NIH) that offer free large-scale genotyping to outstanding genotype/phenotype databases.
2) take the lead in large multinational consortia that pool data for genome-wide screening in mega- and meta-analyses for genes involved in inflammation, depression and cardiovascular disease.