Search

Your search keyword '"Meulenbelt, I."' showing total 856 results
Start Over Author "Meulenbelt, I."
856 results on '"Meulenbelt, I."'

2. NMR metabolomics-guided DNA methylation mortality predictors

Author

Geleijnse, J.M., Boersma, E., van Spil, W.E., van Greevenbroek, M.M.J., Stehouwer, C.D.A., van der Kallen, C.J.H., Arts, I.C.W., Rutters, F., Beulens, J.W.J., Muilwijk, M., Elders, P.J.M., 't Hart, L.M., Ghanbari, M., Ikram, M.A., Netea, M.G., Kloppenburg, M., Ramos, Y.F.M., Bomer, N., Meulenbelt, I., Stronks, K., Snijder, M.B., Zwinderman, A.H., Heijmans, B.T., Lumey, L.H., Wijmenga, C., Fu, J., Zhernakova, A., Deelen, J., Mooijaart, S.P., Beekman, M., Slagboom, P.E., Onderwater, G.L.J., van den Maagdenberg, A.M.J.M., Terwindt, G.M., Thesing, C., Bot, M., Penninx, B.W.J.H., Trompet, S., Jukema, J.W., Sattar, N., van der Horst, I.C.C., van der Harst, P., So-Osman, C., van Hilten, J.A., Nelissen, R.G.H.H., Höfer, I.E., Asselbergs, F.W., Scheltens, P., Teunissen, C.E., van der Flier, W.M., van Dongen, J., Pool, R., Willemsen, A.H.M., Boomsma, D.I., Suchiman, H.E.D., Barkey Wolf, J.J.H., Cats, D., Mei, H., Slofstra, M., Swertz, M., Reinders, M.J.T., van den Akker, E.B., Bizzarri, Daniele, Reinders, Marcel J.T., Kuiper, Lieke, Beekman, Marian, Deelen, Joris, van Meurs, Joyce B.J., van Dongen, Jenny, Pool, René, Boomsma, Dorret I., Ghanbari, Mohsen, Franke, Lude, Slagboom, Pieternella E., and van den Akker, Erik B.

Published
2024
Full Text
View/download PDF

4. NMR metabolomics-guided DNA methylation mortality predictors

Author

Bizzarri, Daniele, Reinders, Marcel J.T., Kuiper, Lieke, Beekman, Marian, Deelen, Joris, van Meurs, Joyce B.J., van Dongen, Jenny, Pool, René, Boomsma, D. I., Ghanbari, M., Franke, Lude, Geleijnse, J. M., Boersma, E., van Spil, W. E., van Greevenbroek, M. M.J., Stehouwer, C. D.A., van der Kallen, C. J.H., Arts, I. C.W., Rutters, F., Beulens, J. W.J., Muilwijk, M., Elders, P. J.M., 't Hart, L. M., Ikram, M. A., Netea, M. G., Kloppenburg, M., Ramos, Y. F.M., Bomer, N., Meulenbelt, I., Stronks, K., Snijder, M. B., Zwinderman, A. H., Heijmans, B. T., Lumey, L. H., Fu, J., Deelen, J., Mooijaart, S. P., Beekman, M., Bot, M., Trompet, S., van der Horst, I. C.C., So-Osman, C., Nelissen, R. G.H.H., Teunissen, C. E., van Dongen, J., Willemsen, A. H.M., Mei, H., Reinders, M. J.T., van den Akker, E. B., Bizzarri, Daniele, Reinders, Marcel J.T., Kuiper, Lieke, Beekman, Marian, Deelen, Joris, van Meurs, Joyce B.J., van Dongen, Jenny, Pool, René, Boomsma, D. I., Ghanbari, M., Franke, Lude, Geleijnse, J. M., Boersma, E., van Spil, W. E., van Greevenbroek, M. M.J., Stehouwer, C. D.A., van der Kallen, C. J.H., Arts, I. C.W., Rutters, F., Beulens, J. W.J., Muilwijk, M., Elders, P. J.M., 't Hart, L. M., Ikram, M. A., Netea, M. G., Kloppenburg, M., Ramos, Y. F.M., Bomer, N., Meulenbelt, I., Stronks, K., Snijder, M. B., Zwinderman, A. H., Heijmans, B. T., Lumey, L. H., Fu, J., Deelen, J., Mooijaart, S. P., Beekman, M., Bot, M., Trompet, S., van der Horst, I. C.C., So-Osman, C., Nelissen, R. G.H.H., Teunissen, C. E., van Dongen, J., Willemsen, A. H.M., Mei, H., Reinders, M. J.T., and van den Akker, E. B.

Abstract

Background: 1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals. Methods: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors. Findings: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates. Interpretation: The addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal. Funding: BBMRI-NL, X-omics, VOILA, Medical Delta, NWO, ERC.

Published
2024

5. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author

Sterenborg, R.B.T.M., Steinbrenner, I., Li, Yong, Bujnis, M.N., Naito, T., Marouli, E., Galesloot, T.E., Babajide, O., Andreasen, L., Astrup, A., Åsvold, B.O., Bandinelli, S., Beekman, M., Beilby, J.P., Bork-Jensen, J., Boutin, T., Brody, J.A., Brown, S.J., Brumpton, B., Campbell, P.J., Cappola, A.R., Ceresini, G., Chaker, L., Chasman, D.I., Concas, M.P., Coutinho de Almeida, Rodrigo, Cross, S.M., Cucca, F., Deary, I.J., Kjaergaard, A.D., Echouffo Tcheugui, J.B., Ellervik, C., Eriksson, J.G., Ferrucci, L., Freudenberg, J., Fuchsberger, C., Gieger, C., Giulianini, F., Gögele, M., Graham, S.E., Grarup, N., Gunjača, I., Hansen, T., Harding, B.N., Harris, S.E., Haunsø, S., Hayward, C., Hui, J., Ittermann, T., Jukema, J.W., Kajantie, E., Kanters, J.K., Kårhus, L.L., Kiemeney, L.A.L.M., Kühnel, B., Lahti, J., Langenberg, C., Lapauw, B., Leese, G., Li, Shuo, Liewald, D.C.M., Linneberg, A., Lominchar, J.V.T., Luan, Jian'an, Martin, N.G., Matana, A., Meima, M.E., Meitinger, T., Meulenbelt, I., Mitchell, B.D., Møllehave, L.T., Mora, S., Naitza, S., Nauck, M., Netea-Maier, R.T., Noordam, R., Nursyifa, C., Okada, Y., Onano, S., Papadopoulou, A., Palmer, C.N.A., Pattaro, C., Pedersen, O., Peters, A., Pietzner, M., Polašek, O., Pramstaller, P.P., Psaty, B.M., Punda, A., Ray, D., Redmond, P., Richards, J.B., Ridker, P.M., Russ, T.C., Ryan, K.A., Olesen, M.S., Schultheiss, U.T., Selvin, E., Siddiqui, M.K., Teumer, A., Medici, M., Sterenborg, R.B.T.M., Steinbrenner, I., Li, Yong, Bujnis, M.N., Naito, T., Marouli, E., Galesloot, T.E., Babajide, O., Andreasen, L., Astrup, A., Åsvold, B.O., Bandinelli, S., Beekman, M., Beilby, J.P., Bork-Jensen, J., Boutin, T., Brody, J.A., Brown, S.J., Brumpton, B., Campbell, P.J., Cappola, A.R., Ceresini, G., Chaker, L., Chasman, D.I., Concas, M.P., Coutinho de Almeida, Rodrigo, Cross, S.M., Cucca, F., Deary, I.J., Kjaergaard, A.D., Echouffo Tcheugui, J.B., Ellervik, C., Eriksson, J.G., Ferrucci, L., Freudenberg, J., Fuchsberger, C., Gieger, C., Giulianini, F., Gögele, M., Graham, S.E., Grarup, N., Gunjača, I., Hansen, T., Harding, B.N., Harris, S.E., Haunsø, S., Hayward, C., Hui, J., Ittermann, T., Jukema, J.W., Kajantie, E., Kanters, J.K., Kårhus, L.L., Kiemeney, L.A.L.M., Kühnel, B., Lahti, J., Langenberg, C., Lapauw, B., Leese, G., Li, Shuo, Liewald, D.C.M., Linneberg, A., Lominchar, J.V.T., Luan, Jian'an, Martin, N.G., Matana, A., Meima, M.E., Meitinger, T., Meulenbelt, I., Mitchell, B.D., Møllehave, L.T., Mora, S., Naitza, S., Nauck, M., Netea-Maier, R.T., Noordam, R., Nursyifa, C., Okada, Y., Onano, S., Papadopoulou, A., Palmer, C.N.A., Pattaro, C., Pedersen, O., Peters, A., Pietzner, M., Polašek, O., Pramstaller, P.P., Psaty, B.M., Punda, A., Ray, D., Redmond, P., Richards, J.B., Ridker, P.M., Russ, T.C., Ryan, K.A., Olesen, M.S., Schultheiss, U.T., Selvin, E., Siddiqui, M.K., Teumer, A., and Medici, M.

Abstract

Contains fulltext : 304858.pdf (Publisher’s version ) (Open Access), To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Published
2024

6. Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls

Author

Beekman, M., Suchiman, H.E.D., Deelen, J., Amin, N., Beulens, J.W., van der Bom, J.A., Bomer, N., Demirkan, A., van Hilten, J.A., Meessen, J.M.T.A., Pool, R., 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., ’t Hart, L.M., van den Maagdenberg, A.M.J.M., van der Harst, P., van der Horst, I.C.C., van der Kallen, C.J.H., van Greevenbroek, M.M.J., van Spil, W.E., Wijmenga, C., Zwinderman, A.H., Zhernikova, A., Jukema, J.W., Sattar, N., Bot, Mariska, Milaneschi, Yuri, Al-Shehri, Tahani, Amin, Najaf, Garmaeva, Sanzhima, Onderwater, Gerrit L.J., Pool, Rene, Thesing, Carisha S., Vijfhuizen, Lisanne S., Vogelzangs, Nicole, Arts, Ilja C.W., Demirkan, Ayse, van Duijn, Cornelia, van Greevenbroek, Marleen, van der Kallen, Carla J.H., Köhler, Sebastian, Ligthart, Lannie, van den Maagdenberg, Arn M.J.M., Mook-Kanamori, Dennis O., de Mutsert, Renée, Tiemeier, Henning, Schram, Miranda T., Stehouwer, Coen D.A., Terwindt, Gisela M., Willems van Dijk, Ko, Fu, Jingyuan, Zhernakova, Alexandra, Beekman, Marian, Slagboom, P. Eline, Boomsma, Dorret I., and Penninx, Brenda W.J.H.

Published
2020
Full Text
View/download PDF

7. A genome-wide association study of anorexia nervosa

Author

Boraska, V, Franklin, CS, Floyd, JAB, Thornton, LM, Huckins, LM, Southam, L, Rayner, NW, Tachmazidou, I, Klump, KL, Treasure, J, Lewis, CM, Schmidt, U, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, P, Adan, RAH, Kas, MJH, Favaro, A, Santonastaso, P, Fernández-Aranda, F, Gratacos, M, Rybakowski, F, Dmitrzak-Weglarz, M, Kaprio, J, Keski-Rahkonen, A, Raevuori, A, Van Furth, EF, Slof-Op 't Landt, MCT, Hudson, JI, Reichborn-Kjennerud, T, Knudsen, GPS, Monteleone, P, Kaplan, AS, Karwautz, A, Hakonarson, H, Berrettini, WH, Guo, Y, Li, D, Schork, NJ, Komaki, G, Ando, T, Inoko, H, Esko, T, Fischer, K, Männik, K, Metspalu, A, Baker, JH, Cone, RD, Dackor, J, DeSocio, JE, Hilliard, CE, O'Toole, JK, Pantel, J, Szatkiewicz, JP, Taico, C, Zerwas, S, Trace, SE, Davis, OSP, Helder, S, Bühren, K, Burghardt, R, de Zwaan, M, Egberts, K, Ehrlich, S, Herpertz-Dahlmann, B, Herzog, W, Imgart, H, Scherag, A, Scherag, S, Zipfel, S, Boni, C, Ramoz, N, Versini, A, Brandys, MK, Danner, UN, de Kovel, C, Hendriks, J, Koeleman, BPC, Ophoff, RA, Strengman, E, van Elburg, AA, Bruson, A, Clementi, M, Degortes, D, Forzan, M, Tenconi, E, Docampo, E, Escaramís, G, Jiménez-Murcia, S, Lissowska, J, Rajewski, A, Szeszenia-Dabrowska, N, Slopien, A, Hauser, J, Karhunen, L, Meulenbelt, I, Slagboom, PE, Tortorella, A, and Maj, M

Subjects
Anorexia, Mental Health, Serious Mental Illness, Human Genome, Eating Disorders, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Anorexia Nervosa, Asian People, Calcineurin, Carrier Proteins, Case-Control Studies, Cullin Proteins, Female, Genome-Wide Association Study, Guanine Nucleotide Exchange Factors, Humans, Japan, Male, Meta-Analysis as Topic, Nuclear Proteins, Polymorphism, Single Nucleotide, White People, anorexia nervosa, body mass index, eating disorders, genome-wide association study, GWAS, metabolic, Wellcome Trust Case Control Consortium 3, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Published
2014

9. Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study

Author

Panoutsopoulou, K, Southam, L, Elliott, KS, Wrayner, N, Zhai, G, Beazley, C, Thorleifsson, G, Arden, NK, Carr, A, Chapman, K, Deloukas, P, Doherty, M, McCaskie, A, Ollier, WER, Ralston, SH, Spector, TD, Valdes, AM, Wallis, GA, Wilkinson, JM, Arden, E, Battley, K, Blackburn, H, Blanco, FJ, Bumpstead, S, Cupples, LA, Day-Williams, AG, Dixon, K, Doherty, SA, Esko, T, Evangelou, E, Felson, D, Gomez-Reino, JJ, Gonzalez, A, Gordon, A, Gwilliam, R, Halldorsson, BV, Hauksson, VB, Hofman, A, Hunt, SE, Ioannidis, JPA, Ingvarsson, T, Jonsdottir, I, Jonsson, H, Keen, R, Kerkhof, HJM, Kloppenburg, MG, Koller, N, Lakenberg, N, Lane, NE, Lee, AT, Metspalu, A, Meulenbelt, I, Nevitt, MC, O'Neill, F, Parimi, N, Potter, SC, Rego-Perez, I, Riancho, JA, Sherburn, K, Slagboom, PE, Stefansson, K, Styrkarsdottir, U, Sumillera, M, Swift, D, Thorsteinsdottir, U, Tsezou, A, Uitterlinden, AG, van Meurs, JBJ, Watkins, B, Wheeler, M, Mitchell, S, Zhu, Y, Zmuda, JM, Consortium, arcOGEN, Zeggini, E, and Loughlin, J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Arthritis, Genetics, Prevention, Aging, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Musculoskeletal, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Osteoarthritis, Hip, Osteoarthritis, Knee, Polymorphism, Single Nucleotide, arcOGEN Consortium, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectivesThe genetic aetiology of osteoarthritis has not yet been elucidated. To enable a well-powered genome-wide association study (GWAS) for osteoarthritis, the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome-wide association scan. Here the authors report the findings of the stage 1 interim analysis.MethodsThe authors have performed a genome-wide association scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based controls from the UK. Replication of promising signals was carried out in silico in five further scans (44,449 individuals), and de novo in 14 534 independent samples, all of European descent.ResultsNone of the association signals the authors identified reach genome-wide levels of statistical significance, therefore stressing the need for corroboration in sample sets of a larger size. Application of analytical approaches to examine the allelic architecture of disease to the stage 1 genome-wide association scan data suggests that osteoarthritis is a highly polygenic disease with multiple risk variants conferring small effects.ConclusionsIdentifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.

Published
2011

15. Application of 3D human in vitro osteoarthritic chondrocyte models to study CCN4/WISP1 and Wnt signaling

Author

Kraan, P.M. van der, Meulenbelt, I., Bosch, M.H.J. van den, Ramos, Y.F.M., Timmermans, R.G.M., Kraan, P.M. van der, Meulenbelt, I., Bosch, M.H.J. van den, Ramos, Y.F.M., and Timmermans, R.G.M.

Abstract

Radboud University, 07 november 2023, Promotores : Kraan, P.M. van der, Meulenbelt, I. Co-promotores : Bosch, M.H.J. van den, Ramos, Y.F.M., Item does not contain fulltext

Published
2023

18. Large scale meta-analysis of urinary C-terminal telopeptide, serum cartilage oligomeric protein and matrix metalloprotease degraded type II collagen and their role in prevalence, incidence and progression of osteoarthritis

Author

Valdes, A.M., Meulenbelt, I., Chassaing, E., Arden, N.K., Bierma-Zeinstra, S., Hart, D., Hofman, A., Karsdal, M., Kloppenburg, M., Kroon, H.M., Slagboom, E.P., Spector, T.D., Uitterlinden, A.G., van Meurs, J.B., and Bay-Jensen, A.C.

Published
2014
Full Text
View/download PDF

19. Sex Differences in Sum Scores May Be Hard to Interpret: The Importance of Measurement Invariance

Author

Slof-Op 't Landt, M. C. T., van Furth, E. F., Rebollo-Mesa, I., Bartels, M., van Beijsterveldt, C. E. M., Slagboom, P. E., Boomsma, D. I., Meulenbelt, I., and Dolan, C. V.

Abstract

In most assessment instruments, distinct items are designed to measure a trait, and the sum score of these items serves as an approximation of an individual's trait score. In interpreting group differences with respect to sum scores, the instrument should measure the same underlying trait across groups (e.g., male/female, young/old). Differences with respect to the sum score should accurately reflect differences in the latent trait of interest. A necessary condition for this is that the instrument is measurement invariant. In the current study, the authors illustrate a stepwise approach for testing measurement invariance with respect to sex in a four-item instrument designed to assess disordered eating behavior in a large epidemiological sample (1,195 men and 1,507 women). This approach can be applied to other phenotypes for which group differences are expected. Any analysis of such variables may be subject to measurement bias if a lack of measurement invariance between grouping variables goes undetected. (Contains 3 tables and 1 note.)

Published
2009
Full Text
View/download PDF

20. A human in vitro 3D neo-cartilage model to explore the response of OA risk genes to hyper-physiological mechanical stress

Author

Timmermans, R.G.M., Bloks, N.G.C., Tuerlings, M., Hoolwerff, M. van, Nelissen, R.G., Wal, R.J.P. van der, Kraan, P.M. van der, Blom, A.B., Bosch, M.H.J. van den, Ramos, Y.F.M., Meulenbelt, I., Timmermans, R.G.M., Bloks, N.G.C., Tuerlings, M., Hoolwerff, M. van, Nelissen, R.G., Wal, R.J.P. van der, Kraan, P.M. van der, Blom, A.B., Bosch, M.H.J. van den, Ramos, Y.F.M., and Meulenbelt, I.

Abstract

Contains fulltext : 248968.pdf (Publisher’s version ) (Open Access)

Published
2022

23. FUNCTIONAL GENOMICS HIGHLIGHTS ROLE FOR OSTEOARTHRITIS SUSCEPTIBILITY GENE WWP2 IN CARTILAGE MATRIX DEPOSITION

Author

Tuerlings, M., primary, Janssen, G., additional, Boone, I., additional, van Hoolwerff, M., additional, Ruiz, A. Rodriguez, additional, Houtman, E., additional, Suchiman, E., additional, van der Wal, R., additional, Nelissen, R., additional, Coutinho de Almeida, R., additional, van Veelen, P., additional, Ramos, Y., additional, and Meulenbelt, I., additional

Published
2022
Full Text
View/download PDF

30. AN EPIGENOME-WIDE VIEW OF OSTEOARTHRITIS IN PRIMARY TISSUES

Author

Kreitmaier, P., primary, Suderman, M., additional, Southam, L., additional, Coutinho de Almeida, R., additional, Hatzikotoulas, K., additional, Meulenbelt, I., additional, Steinberg, J., additional, Relton, C., additional, Wilkinson, J.M., additional, and Zeggini, E., additional

Published
2022
Full Text
View/download PDF

32. Genetics and Not Shared Environment Explains Familial Resemblance in Adult Metabolomics Data

Author

Pool, Rene, Hagenbeek, Fiona A., Hendriks, Anne M., van Dongen, Jenny, Willemsen, Gonneke, de Geus, Eco, van Dijk, Ko Willems, Verhoeven, Aswin, Suchiman, H. Eka, Beekman, Marian, Slagboom, P. Eline, Harms, Amy C., Hankemeier, Thomas, Boomsma, Dorret, I, Beekman, M., Suchiman, H. E. D., Amin, N., Beulens, J. W., van der Bom, J. A., Bomer, N., Demirkan, A., van Hilten, J. A., Meessen, J. M. T. A., Pool, R., 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., 't Hart, L. M., van den Maagdenberg, A. M. J. M., van der Harst, P., van der Horst, I. C. C., van der Kallen, C. J. H., van Greevenbroek, M. M. J., van Spil, W. E., Wijmenga, C., Zwinderman, A. H., Zhernikova, A., Jukema, J. W., Wolf, J. J. H. Barkey, Cats, D., Mei, H., Slofstra, M., Swertz, M., van den Akker, E. B., Deelen, J., Reinders, M. J. T., Boomsma, D., I, van Duijn, C. M., Slagboom, P. E., Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (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), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Molecular Neuroscience and Ageing Research (MOLAR), Cardiovascular Centre (CVC), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Medical Microbiology and Infection Prevention, Graduate School, Tytgat Institute for Liver and Intestinal Research, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Obstetrics and Gynaecology, Cardiology, Public and occupational health, Gastroenterology and Hepatology, Paediatric Endocrinology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Epidemiology and Data Science, Obstetrics and gynaecology, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, Anatomy and neurosciences, Anesthesiology, General practice, Internal medicine, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Reproduction & Development (AR&D), AMS - Musculoskeletal Health, AMS - Tissue Function & Regeneration, Rheumatology, Gastroenterology and hepatology, APH - Aging & Later Life, and APH - Digital Health

Subjects
Male, Netherlands Twin Register (NTR), 0301 basic medicine, Shared environment, Metabolite, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Genome-wide association study, heritability, METABOLITES, Keywords: Classical twin design, chemistry.chemical_compound, 0302 clinical medicine, metabolite classes, Twins, Dizygotic, EPIDEMIOLOGY, Classical twin design, Genetics (clinical), Genetics, HERITABILITY, shared environment, Obstetrics and Gynecology, Phenotype, Quartile, Metabolome, Female, Adult, Dizygotic twin, POWER, TWIN, Environment, Biology, enrichment analysis, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Metabolomics, AGE, Diseases in Twins, Humans, Family, GENOME-WIDE ASSOCIATION, Classical twin design [Keywords], Twins, Monozygotic, PROFILES, Heritability, Diet, Metabolomics data, 030104 developmental biology, chemistry, Pediatrics, Perinatology and Child Health, Gene-Environment Interaction, 030217 neurology & neurosurgery
Abstract

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term ‘metabolomics’ refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.

Published
2020
Full Text
View/download PDF

33. Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

Author

Bjornsdottir, G. Stefansdottir, L. Thorleifsson, G. Sulem, P. Norland, K. Ferkingstad, E. Oddsson, A. Zink, F. Lund, S.H. Nawaz, M.S. Bragi Walters, G. Skuladottir, A.T. Gudjonsson, S.A. Einarsson, G. Halldorsson, G.H. Bjarnadottir, V. Sveinbjornsson, G. Helgadottir, A. Styrkarsdottir, U. Gudmundsson, L.J. Pedersen, O.B. Hansen, T.F. Werge, T. Banasik, K. Troelsen, A. Skou, S.T. Thørner, L.W. Erikstrup, C. Nielsen, K.R. Mikkelsen, S. Andersen, S. Brunak, S. Burgdorf, K. Hjalgrim, H. Jemec, G. Jennum, P. Johansson, P.I. Nielsen, K.R. Nyegaard, M. Bruun, M.T. Pedersen, O.B. Dinh, K.M. Sørensen, E. Ostrowski, S. Johansson, P.I. Gudbjartsson, D. Stefánsson, H. Þorsteinsdóttir, U. Larsen, M.A.H. Didriksen, M. Sækmose, S. Zeggini, E. Hatzikotoulas, K. Southam, L. Gilly, A. Barysenka, A. van Meurs, J.B.J. Boer, C.G. Uitterlinden, A.G. Styrkársdóttir, U. Stefánsdóttir, L. Jonsson, H. Ingvarsson, T. Esko, T. Mägi, R. Teder-Laving, M. Ikegawa, S. Terao, C. Takuwa, H. Meulenbelt, I. Coutinho de Almeida, R. Kloppenburg, M. Tuerlings, M. Slagboom, P.E. Nelissen, R.R.G.H.H. Valdes, A.M. Mangino, M. Tsezou, A. Zengini, E. Alexiadis, G. Babis, G.C. Cheah, K.S.E. Wu, T.T. Samartzis, D. Cheung, J.P.Y. Sham, P.C. Kraft, P. Kang, J.H. Hveem, K. Zwart, J.-A. Luetge, A. Skogholt, A.H. Johnsen, M.B. Thomas, L.F. Winsvold, B. Gabrielsen, M.E. Lee, M.T.M. Zhang, Y. Lietman, S.A. Shivakumar, M. Smith, G.D. Tobias, J.H. Hartley, A. Gaunt, T.R. Zheng, J. Wilkinson, J.M. Steinberg, J. Morris, A.P. Jonsdottir, I. Bjornsson, A. Olafsson, I.H. Ulfarsson, E. Blondal, J. Vikingsson, A. Brunak, S. Ostrowski, S.R. Ullum, H. Thorsteinsdottir, U. Stefansson, H. Gudbjartsson, D.F. Thorgeirsson, T.E. Stefansson, K. DBDS Genetic Consortium GO Consortium

Abstract

Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes. © 2022, The Author(s).

Published
2022

35. Large-scale meta-analysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis

Author

Kerkhof, H.J.M., Doherty, M., Arden, N.K., Abramson, S.B., Attur, M., Bos, S.D., Cooper, C., Dennison, E.M., Doherty, S.A., Evangelou, E., Hart, D.J., Hofman, A., Javaid, K., Kerna, I., Kisand, K., Kloppenburg, M., Krasnokutsky, S., Maciewicz, R.A., Meulenbelt, I., Muir, K.R., Rivadeneira, F., Samuels, J., Sezgin, M., Slagboom, E., Smith, A.J.P., Spector, T.D., Tamm, A., Uitterlinden, A.G., Wheeler, M., Zhai, G., Zhang, W., van Meurs, J.B.J., and Valdes, A.M.

Published
2011
Full Text
View/download PDF

36. Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium

Author

Kerkhof, H.J.M., Meulenbelt, I., Akune, T., Arden, N.K., Aromaa, A., Bierma-Zeinstra, S.M.A., Carr, A., Cooper, C., Dai, J., Doherty, M., Doherty, S.A., Felson, D., Gonzalez, A., Gordon, A., Harilainen, A., Hart, D.J., Hauksson, V.B., Heliovaara, M., Hofman, A., Ikegawa, S., Ingvarsson, T., Jiang, Q., Jonsson, H., Jonsdottir, I., Kawaguchi, H., Kloppenburg, M., Kujala, U.M., Lane, N.E., Leino-Arjas, P., Lohmander, L.S., Luyten, F.P., Malizos, K.N., Nakajima, M., Nevitt, M.C., Pols, H.A.P., Rivadeneira, F., Shi, D., Slagboom, E., Spector, T.D., Stefansson, K., Sudo, A., Tamm, A., Tamm, A.E., Tsezou, A., Uchida, A., Uitterlinden, A.G., Wilkinson, J.M., Yoshimura, N., Valdes, A.M., and van Meurs, J.B.J.

Published
2011
Full Text
View/download PDF

39. How does hip osteoarthritis differ from knee osteoarthritis?

Author

Hall, M., primary, van der Esch, M., additional, Hinman, R.S., additional, Peat, G., additional, de Zwart, A., additional, Quicke, J.G., additional, Runhaar, J., additional, Knoop, J., additional, van der Leeden, M., additional, de Rooij, M., additional, Meulenbelt, I., additional, Vliet Vlieland, T., additional, Lems, W.F., additional, Holden, M.A., additional, Foster, N.E., additional, and Bennell, K.L., additional

Published
2022
Full Text
View/download PDF

44. Higher thyroid stimulating hormone leads to cardiovascular disease and an unfavorable lipid profile: EVidence from multi-cohort Mendelian randomization and metabolomic profiling

Author

Van Vliet, N.A., primary, Bos, M.M., additional, Thesing, C.S., additional, Chaker, L., additional, Pietzner, M., additional, Houtman, E., additional, Neville, M.J., additional, Li-Gao, R., additional, Trompet, S., additional, Mustafa, R., additional, Ahmadizar, F., additional, Beekman, M., additional, Bot, M., additional, Budde, K., additional, Christodoulides, C., additional, Dehghan, A., additional, Delles, C., additional, Elliott, P., additional, Evangelou, M., additional, Gao, H., additional, Ghanbari, M., additional, Van Herwaarden, A.E., additional, Ikram, M.A., additional, Jaeger, M., additional, Jukema, J.W., additional, Karaman, I., additional, Karpe, F., additional, Kloppenburg, M., additional, Meessen, J.M.T.A., additional, Meulenbelt, I., additional, Milaneschi, Y., additional, Mooijaart, S.P., additional, Mook-Kanamori, D.O., additional, Netea, M.G., additional, Netea-Maier, R.T., additional, Peeters, R.P., additional, Penninx, B.W.J.H., additional, Sattar, N., additional, Slagboom, P.E., additional, Suchiman, H.E.D., additional, Völzke, H., additional, Van Dijk, K. Willems, additional, and Noordam, R., additional

Published
2021
Full Text
View/download PDF

45. Characterization of dynamic changes in Matrix Gla Protein (MGP) gene expression as function of genetic risk alleles, osteoarthritis relevant stimuli, and the vitamin K inhibitor warfarin

Author

Houtman, E., primary, Coutinho de Almeida, R., additional, Tuerlings, M., additional, Suchiman, H.E.D., additional, Broekhuis, D., additional, Nelissen, R.G.H.H., additional, Ramos, Y.F.M., additional, van Meurs, J.B.J., additional, and Meulenbelt, I., additional

Published
2021
Full Text
View/download PDF

46. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

Munn-Chernoff, M.A. Johnson, E.C. Chou, Y.-L. Coleman, J.R.I. Thornton, L.M. Walters, R.K. Yilmaz, Z. Baker, J.H. Hübel, C. Gordon, S. Medland, S.E. Watson, H.J. Gaspar, H.A. Bryois, J. Hinney, A. Leppä, V.M. Mattheisen, M. Ripke, S. Yao, S. Giusti-Rodríguez, P. Hanscombe, K.B. Adan, R.A.H. Alfredsson, L. Ando, T. Andreassen, O.A. Berrettini, W.H. Boehm, I. Boni, C. Boraska Perica, V. Buehren, K. Burghardt, R. Cassina, M. Cichon, S. Clementi, M. Cone, R.D. Courtet, P. Crow, S. Crowley, J.J. Danner, U.N. Davis, O.S.P. de Zwaan, M. Dedoussis, G. Degortes, D. DeSocio, J.E. Dick, D.M. Dikeos, D. Dina, C. Dmitrzak-Weglarz, M. Docampo, E. Duncan, L.E. Egberts, K. Ehrlich, S. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Favaro, A. Fernández-Aranda, F. Fichter, M.M. Fischer, K. Föcker, M. Foretova, L. Forstner, A.J. Forzan, M. Franklin, C.S. Gallinger, S. Giegling, I. Giuranna, J. Gonidakis, F. Gorwood, P. Gratacos Mayora, M. Guillaume, S. Guo, Y. Hakonarson, H. Hatzikotoulas, K. Hauser, J. Hebebrand, J. Helder, S.G. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Huckins, L.M. Hudson, J.I. Imgart, H. Inoko, H. Janout, V. Jiménez-Murcia, S. Julià, A. Kalsi, G. Kaminská, D. Karhunen, L. Karwautz, A. Kas, M.J.H. Kennedy, J.L. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Klump, K.L. Knudsen, G.P.S. La Via, M.C. Le Hellard, S. Levitan, R.D. Li, D. Lilenfeld, L. Lin, B.D. Lissowska, J. Luykx, J. Magistretti, P.J. Maj, M. Mannik, K. Marsal, S. Marshall, C.R. Mattingsdal, M. McDevitt, S. McGuffin, P. Metspalu, A. Meulenbelt, I. Micali, N. Mitchell, K. Monteleone, A.M. Monteleone, P. Nacmias, B. Navratilova, M. Ntalla, I. O'Toole, J.K. Ophoff, R.A. Padyukov, L. Palotie, A. Pantel, J. Papezova, H. Pinto, D. Rabionet, R. Raevuori, A. Ramoz, N. Reichborn-Kjennerud, T. Ricca, V. Ripatti, S. Ritschel, F. Roberts, M. Rotondo, A. Rujescu, D. Rybakowski, F. Santonastaso, P. Scherag, A. Scherer, S.W. Schmidt, U. Schork, N.J. Schosser, A. Seitz, J. Slachtova, L. Slagboom, P.E. Slof-Op't Landt, M.C.T. Slopien, A. Sorbi, S. Świątkowska, B. Szatkiewicz, J.P. Tachmazidou, I. Tenconi, E. Tortorella, A. Tozzi, F. Treasure, J. Tsitsika, A. Tyszkiewicz-Nwafor, M. Tziouvas, K. van Elburg, A.A. van Furth, E.F. Wagner, G. Walton, E. Widen, E. Zeggini, E. Zerwas, S. Zipfel, S. Bergen, A.W. Boden, J.M. Brandt, H. Crawford, S. Halmi, K.A. Horwood, L.J. Johnson, C. Kaplan, A.S. Kaye, W.H. Mitchell, J. Olsen, C.M. Pearson, J.F. Pedersen, N.L. Strober, M. Werge, T. Whiteman, D.C. Woodside, D.B. Grove, J. Henders, A.K. Larsen, J.T. Parker, R. Petersen, L.V. Jordan, J. Kennedy, M.A. Birgegård, A. Lichtenstein, P. Norring, C. Landén, M. Mortensen, P.B. Polimanti, R. McClintick, J.N. Adkins, A.E. Aliev, F. Bacanu, S.-A. Batzler, A. Bertelsen, S. Biernacka, J.M. Bigdeli, T.B. Chen, L.-S. Clarke, T.-K. Degenhardt, F. Docherty, A.R. Edwards, A.C. Foo, J.C. Fox, L. Frank, J. Hack, L.M. Hartmann, A.M. Hartz, S.M. Heilmann-Heimbach, S. Hodgkinson, C. Hoffmann, P. Hottenga, J.-J. Konte, B. Lahti, J. Lahti-Pulkkinen, M. Lai, D. Ligthart, L. Loukola, A. Maher, B.S. Mbarek, H. McIntosh, A.M. McQueen, M.B. Meyers, J.L. Milaneschi, Y. Palviainen, T. Peterson, R.E. Ryu, E. Saccone, N.L. Salvatore, J.E. Sanchez-Roige, S. Schwandt, M. Sherva, R. Streit, F. Strohmaier, J. Thomas, N. Wang, J.-C. Webb, B.T. Wedow, R. Wetherill, L. Wills, A.G. Zhou, H. Boardman, J.D. Chen, D. Choi, D.-S. Copeland, W.E. Culverhouse, R.C. Dahmen, N. Degenhardt, L. Domingue, B.W. Frye, M.A. Gäebel, W. Hayward, C. Ising, M. Keyes, M. Kiefer, F. Koller, G. Kramer, J. Kuperman, S. Lucae, S. Lynskey, M.T. Maier, W. Mann, K. Männistö, S. Müller-Myhsok, B. Murray, A.D. Nurnberger, J.I. Preuss, U. Räikkönen, K. Reynolds, M.D. Ridinger, M. Scherbaum, N. Schuckit, M.A. Soyka, M. Treutlein, J. Witt, S.H. Wodarz, N. Zill, P. Adkins, D.E. Boomsma, D.I. Bierut, L.J. Brown, S.A. Bucholz, K.K. Costello, E.J. de Wit, H. Diazgranados, N. Eriksson, J.G. Farrer, L.A. Foroud, T.M. Gillespie, N.A. Goate, A.M. Goldman, D. Grucza, R.A. Hancock, D.B. Harris, K.M. Hesselbrock, V. Hewitt, J.K. Hopfer, C.J. Iacono, W.G. Johnson, E.O. Karpyak, V.M. Kendler, K.S. Kranzler, H.R. Krauter, K. Lind, P.A. McGue, M. MacKillop, J. Madden, P.A.F. Maes, H.H. Magnusson, P.K.E. Nelson, E.C. Nöthen, M.M. Palmer, A.A. Penninx, B.W.J.H. Porjesz, B. Rice, J.P. Rietschel, M. Riley, B.P. Rose, R.J. Shen, P.-H. Silberg, J. Stallings, M.C. Tarter, R.E. Vanyukov, M.M. Vrieze, S. Wall, T.L. Whitfield, J.B. Zhao, H. Neale, B.M. Wade, T.D. Heath, A.C. Montgomery, G.W. Martin, N.G. Sullivan, P.F. Kaprio, J. Breen, G. Gelernter, J. Edenberg, H.J. Bulik, C.M. Agrawal, A.

Subjects
mental disorders
Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors. © 2020 Society for the Study of Addiction

Published
2021

47. Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling

Author

Vliet, N.A. van, Bos, M.M., Thesing, C.S., Chaker, L., Pietzner, M., Houtman, E., Neville, M.J., Li-Gao, R., Trompet, S., Mustafa, R., Ahmadizar, F., Beekman, M., Bot, M., Budde, K., Christodoulides, C., Dehghan, A., Delles, C., Elliott, P., Evangelou, M., Gao, H., Ghanbari, M., Herwaarden, A.E. van, Ikram, M.Arfan, Jaeger, M., Jukema, J.W., Karaman, I., Karpe, F., Kloppenburg, M., Meessen, J., Meulenbelt, I., Milaneschi, Y., Mooijaart, S.P., Mook-Kanamori, D.O., Netea, M.G., Netea, R.T., Peeters, R.P., Penninx, B., Sattar, N., Slagboom, P.Eline, Suchiman, H. Eka D., Völzke, H., Dijk, K.W van, Noordam, R., Heemst, D. van, Vliet, N.A. van, Bos, M.M., Thesing, C.S., Chaker, L., Pietzner, M., Houtman, E., Neville, M.J., Li-Gao, R., Trompet, S., Mustafa, R., Ahmadizar, F., Beekman, M., Bot, M., Budde, K., Christodoulides, C., Dehghan, A., Delles, C., Elliott, P., Evangelou, M., Gao, H., Ghanbari, M., Herwaarden, A.E. van, Ikram, M.Arfan, Jaeger, M., Jukema, J.W., Karaman, I., Karpe, F., Kloppenburg, M., Meessen, J., Meulenbelt, I., Milaneschi, Y., Mooijaart, S.P., Mook-Kanamori, D.O., Netea, M.G., Netea, R.T., Peeters, R.P., Penninx, B., Sattar, N., Slagboom, P.Eline, Suchiman, H. Eka D., Völzke, H., Dijk, K.W van, Noordam, R., and Heemst, D. van

Abstract

Contains fulltext : 245686.pdf (Publisher’s version ) (Open Access), BACKGROUND: Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. METHODS: Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. RESULTS: Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99-1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96-1.04; p value 0.5

Published
2021

48. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

Munn-Chernoff, MA, Johnson, EC, Chou, YL, Coleman, JRI, Thornton, LM, Walters, RK, Yilmaz, Z, Baker, JH, Hübel, C, Gordon, S, Medland, SE, Watson, HJ, Gaspar, HA, Bryois, J, Hinney, A, Leppä, VM, Mattheisen, M, Ripke, S, Yao, S, Giusti-Rodríguez, P, Hanscombe, KB, Adan, RAH, Alfredsson, L, Ando, T, Andreassen, OA, Berrettini, WH, Boehm, I, Boni, C, Boraska Perica, V, Buehren, K, Burghardt, R, Cassina, M, Cichon, S, Clementi, M, Cone, RD, Courtet, P, Crow, S, Crowley, JJ, Danner, UN, Davis, OS, Zwaan, M, Dedoussis, G, Degortes, D, DeSocio, JE, Dick, DM, Dikeos, D, Dina, C, Dmitrzak-Weglarz, M, Docampo, E, Duncan, LE, Egberts, K, Ehrlich, S, Escaramís, G, Esko, T, Estivill, X, Farmer, A, Favaro, A, Fernández-Aranda, F, Fichter, MM, Fischer, K, Föcker, M, Foretova, L, Forstner, AJ, Forzan, M, Franklin, CS, Gallinger, S, Giegling, I, Giuranna, J, Gonidakis, F, Gorwood, P, Gratacos Mayora, M, Guillaume, S, Guo, Y, Hakonarson, H, Hatzikotoulas, K, Hauser, J, Hebebrand, J, Helder, SG, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Huckins, LM, Hudson, JI, Imgart, H, Inoko, H, Janout, V, Jiménez-Murcia, S, Julià, A, Kalsi, G, Kaminská, D, Karhunen, L, Karwautz, A, Kas, MJH, Kennedy, JL, Keski-Rahkonen, A, Kiezebrink, K, Kim, YR, Klump, KL, Knudsen, GP, La Via, MC, Le Hellard, S, Levitan, RD, Li, D, Lilenfeld, L, Lin, BD, Lissowska, J, Luykx, J, Magistretti, PJ, Maj, M, Mannik, K, Marsal, S, Marshall, CR, Mattingsdal, M, McDevitt, S, McGuffin, P, Metspalu, A, Meulenbelt, I, Micali, N, Mitchell, K, Monteleone, A M, Monteleone, P, Nacmias, B, Navratilova, M, Ntalla, I, O'Toole, JK, Ophoff, Roel, Padyukov, L, Palotie, A, Pantel, J, Papezova, H, Pinto, D, Rabionet, R, Raevuori, A, Ramoz, N, Reichborn-Kjennerud, T, Ricca, V, Ripatti, S, Ritschel, F, Roberts, M, Rotondo, A, Rujescu, D, Rybakowski, F, Santonastaso, P, Scherag, A, Scherer, SW, Schmidt, U, Schork, NJ, Schosser, A, Seitz, J, Slachtova, L, Slagboom, PE, Slof-Op't Landt, MCT, Slopien, A, Sorbi, S, ?wi?tkowska, B, Szatkiewicz, JP, Tachmazidou, I, Tenconi, E, Tortorella, A, Tozzi, F, Treasure, J, Tsitsika, A, Tyszkiewicz-Nwafor, M, Tziouvas, K, van Elburg, AA, van Furth, EF, Wagner, G, Walton, E, Widen, E, Zeggini, E, Zerwas, S, Zipfel, S, Bergen, AW, Boden, JM, Brandt, H, Crawford, S, Halmi, KA, Horwood, LJ, Johnson, C, Kaplan, AS, Kaye, WH, Mitchell, J E, Olsen, CM, Pearson, JF, Pedersen, NL, Strober, M, Werge, T, Whiteman, DC, Woodside, DB, Grove, J, Henders, AK, Larsen, J T, Parker, R, Petersen, LV, Jordan, J, Kennedy, MA, Birgegård, A, Lichtenstein, P, Norring, C, Landén, M, Mortensen, PB, Polimanti, R, McClintick, JN, Adkins, AE, Aliev, F, Bacanu, SA, Batzler, A, Bertelsen, S, Biernacka, JM, Bigdeli, TB, Chen, L S, Clarke, TK, Degenhardt, F, Docherty, AR, Edwards, AC, Foo, JC, Fox, L, Frank, J, Hack, LM, Hartmann, AM, Hartz, SM, Heilmann-Heimbach, S, Hodgkinson, C, Hoffmann, P, Hottenga, JJ, Konte, B, Lahti, J, Lahti-Pulkkinen, M, Lai, D, Ligthart, L, Loukola, A, Maher, BS, Mbarek, H, McIntosh, AM, McQueen, MB, Meyers, JL, Milaneschi, Y, Palviainen, T, Peterson, RE, Ryu, E, Saccone, N L, Salvatore, JE, Sanchez-Roige, S, Schwandt, M, Sherva, R, Streit, F, Strohmaier, J, Thomas, N, Wang, JCY, Webb, BT, Wedow, R, Wetherill, L, Wills, AG, Zhou, H, Boardman, JD, Chen, D, Choi, D S, Copeland, WE, Culverhouse, RC, Dahmen, N, Degenhardt, L, Domingue, BW, Frye, MA, Gäebel, W, Hayward, C, Ising, M, Keyes, M, Kiefer, F, Koller, G, Kramer, J (John), Kuperman, S, Lucae, S, Lynskey, MT, Maier, W, Mann, K, Männistö, S, Müller-Myhsok, B, Murray, AD, Nurnberger, JI, Preuss, U, Räikkönen, K, Reynolds, MD, Ridinger, M, Scherbaum, N, Schuckit, MA, Soyka, M, Treutlein, J, Witt, SH, Wodarz, N, Zill, P, Adkins, DE, Boomsma, DI, Bierut, LJ, Brown, S, Bucholz, KK, Costello, EJ, Wit, HJ, Diazgranados, N, Eriksson, JG, Farrer, LA, Foroud, TM, Gillespie, NA, Goate, AM, Goldman, D, Grucza, RA, Hancock, DB, Harris, KM, Hesselbrock, V, Hewitt, JK, Hopfer, CJ, Iacono, WG, Johnson, E O, Karpyak, VM, Kendler, KS, Kranzler, HR, Krauter, K, Lind, PA, McGue, M, MacKillop, J, Madden, PA, Maes, HH, Magnusson, PKE, Nelson, EC, Nöthen, MM, Palmer, AA, Penninx, BWJH, Porjesz, B, Rice, JP, Rietschel, M, Riley, BP, Rose, RJ, Shen, PH, Silberg, J, Stallings, MC, Tarter, RE, Vanyukov, MM, Vrieze, S, Wall, TL, Whitfield, JB, Zhao, H, Neale, BM, Wade, TD, Heath, AC, Montgomery, GW, Martin, NG, Sullivan, PF, Kaprio, J, Breen, G, Gelernter, J, Edenberg, HJ, Bulik, CM, Agrawal, A, Munn-Chernoff, MA, Johnson, EC, Chou, YL, Coleman, JRI, Thornton, LM, Walters, RK, Yilmaz, Z, Baker, JH, Hübel, C, Gordon, S, Medland, SE, Watson, HJ, Gaspar, HA, Bryois, J, Hinney, A, Leppä, VM, Mattheisen, M, Ripke, S, Yao, S, Giusti-Rodríguez, P, Hanscombe, KB, Adan, RAH, Alfredsson, L, Ando, T, Andreassen, OA, Berrettini, WH, Boehm, I, Boni, C, Boraska Perica, V, Buehren, K, Burghardt, R, Cassina, M, Cichon, S, Clementi, M, Cone, RD, Courtet, P, Crow, S, Crowley, JJ, Danner, UN, Davis, OS, Zwaan, M, Dedoussis, G, Degortes, D, DeSocio, JE, Dick, DM, Dikeos, D, Dina, C, Dmitrzak-Weglarz, M, Docampo, E, Duncan, LE, Egberts, K, Ehrlich, S, Escaramís, G, Esko, T, Estivill, X, Farmer, A, Favaro, A, Fernández-Aranda, F, Fichter, MM, Fischer, K, Föcker, M, Foretova, L, Forstner, AJ, Forzan, M, Franklin, CS, Gallinger, S, Giegling, I, Giuranna, J, Gonidakis, F, Gorwood, P, Gratacos Mayora, M, Guillaume, S, Guo, Y, Hakonarson, H, Hatzikotoulas, K, Hauser, J, Hebebrand, J, Helder, SG, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Huckins, LM, Hudson, JI, Imgart, H, Inoko, H, Janout, V, Jiménez-Murcia, S, Julià, A, Kalsi, G, Kaminská, D, Karhunen, L, Karwautz, A, Kas, MJH, Kennedy, JL, Keski-Rahkonen, A, Kiezebrink, K, Kim, YR, Klump, KL, Knudsen, GP, La Via, MC, Le Hellard, S, Levitan, RD, Li, D, Lilenfeld, L, Lin, BD, Lissowska, J, Luykx, J, Magistretti, PJ, Maj, M, Mannik, K, Marsal, S, Marshall, CR, Mattingsdal, M, McDevitt, S, McGuffin, P, Metspalu, A, Meulenbelt, I, Micali, N, Mitchell, K, Monteleone, A M, Monteleone, P, Nacmias, B, Navratilova, M, Ntalla, I, O'Toole, JK, Ophoff, Roel, Padyukov, L, Palotie, A, Pantel, J, Papezova, H, Pinto, D, Rabionet, R, Raevuori, A, Ramoz, N, Reichborn-Kjennerud, T, Ricca, V, Ripatti, S, Ritschel, F, Roberts, M, Rotondo, A, Rujescu, D, Rybakowski, F, Santonastaso, P, Scherag, A, Scherer, SW, Schmidt, U, Schork, NJ, Schosser, A, Seitz, J, Slachtova, L, Slagboom, PE, Slof-Op't Landt, MCT, Slopien, A, Sorbi, S, ?wi?tkowska, B, Szatkiewicz, JP, Tachmazidou, I, Tenconi, E, Tortorella, A, Tozzi, F, Treasure, J, Tsitsika, A, Tyszkiewicz-Nwafor, M, Tziouvas, K, van Elburg, AA, van Furth, EF, Wagner, G, Walton, E, Widen, E, Zeggini, E, Zerwas, S, Zipfel, S, Bergen, AW, Boden, JM, Brandt, H, Crawford, S, Halmi, KA, Horwood, LJ, Johnson, C, Kaplan, AS, Kaye, WH, Mitchell, J E, Olsen, CM, Pearson, JF, Pedersen, NL, Strober, M, Werge, T, Whiteman, DC, Woodside, DB, Grove, J, Henders, AK, Larsen, J T, Parker, R, Petersen, LV, Jordan, J, Kennedy, MA, Birgegård, A, Lichtenstein, P, Norring, C, Landén, M, Mortensen, PB, Polimanti, R, McClintick, JN, Adkins, AE, Aliev, F, Bacanu, SA, Batzler, A, Bertelsen, S, Biernacka, JM, Bigdeli, TB, Chen, L S, Clarke, TK, Degenhardt, F, Docherty, AR, Edwards, AC, Foo, JC, Fox, L, Frank, J, Hack, LM, Hartmann, AM, Hartz, SM, Heilmann-Heimbach, S, Hodgkinson, C, Hoffmann, P, Hottenga, JJ, Konte, B, Lahti, J, Lahti-Pulkkinen, M, Lai, D, Ligthart, L, Loukola, A, Maher, BS, Mbarek, H, McIntosh, AM, McQueen, MB, Meyers, JL, Milaneschi, Y, Palviainen, T, Peterson, RE, Ryu, E, Saccone, N L, Salvatore, JE, Sanchez-Roige, S, Schwandt, M, Sherva, R, Streit, F, Strohmaier, J, Thomas, N, Wang, JCY, Webb, BT, Wedow, R, Wetherill, L, Wills, AG, Zhou, H, Boardman, JD, Chen, D, Choi, D S, Copeland, WE, Culverhouse, RC, Dahmen, N, Degenhardt, L, Domingue, BW, Frye, MA, Gäebel, W, Hayward, C, Ising, M, Keyes, M, Kiefer, F, Koller, G, Kramer, J (John), Kuperman, S, Lucae, S, Lynskey, MT, Maier, W, Mann, K, Männistö, S, Müller-Myhsok, B, Murray, AD, Nurnberger, JI, Preuss, U, Räikkönen, K, Reynolds, MD, Ridinger, M, Scherbaum, N, Schuckit, MA, Soyka, M, Treutlein, J, Witt, SH, Wodarz, N, Zill, P, Adkins, DE, Boomsma, DI, Bierut, LJ, Brown, S, Bucholz, KK, Costello, EJ, Wit, HJ, Diazgranados, N, Eriksson, JG, Farrer, LA, Foroud, TM, Gillespie, NA, Goate, AM, Goldman, D, Grucza, RA, Hancock, DB, Harris, KM, Hesselbrock, V, Hewitt, JK, Hopfer, CJ, Iacono, WG, Johnson, E O, Karpyak, VM, Kendler, KS, Kranzler, HR, Krauter, K, Lind, PA, McGue, M, MacKillop, J, Madden, PA, Maes, HH, Magnusson, PKE, Nelson, EC, Nöthen, MM, Palmer, AA, Penninx, BWJH, Porjesz, B, Rice, JP, Rietschel, M, Riley, BP, Rose, RJ, Shen, PH, Silberg, J, Stallings, MC, Tarter, RE, Vanyukov, MM, Vrieze, S, Wall, TL, Whitfield, JB, Zhao, H, Neale, BM, Wade, TD, Heath, AC, Montgomery, GW, Martin, NG, Sullivan, PF, Kaprio, J, Breen, G, Gelernter, J, Edenberg, HJ, Bulik, CM, and Agrawal, A

Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotyp

Published
2021

49. Genome-wide association of phenotypes based on clustering patterns of hand osteoarthritis identify WNT9A as novel osteoarthritis gene

Author

Boer, Cindy, Yau, MS, Rice, SJ, Almeida, R, Cheung, K, Styrkarsdottir, U, Southam, L, Broer, Linda, Wilkinson, JM, Uitterlinden, André, Zeggini, E, Felson, D, Loughlin, J, Young, M, Capellini, TD, Meulenbelt, I, van Meurs, Joyce, Boer, Cindy, Yau, MS, Rice, SJ, Almeida, R, Cheung, K, Styrkarsdottir, U, Southam, L, Broer, Linda, Wilkinson, JM, Uitterlinden, André, Zeggini, E, Felson, D, Loughlin, J, Young, M, Capellini, TD, Meulenbelt, I, and van Meurs, Joyce

Abstract

Background Despite recent advances in the understanding of the genetic architecture of osteoarthritis (OA), only two genetic loci have been identified for OA of the hand, in part explained by the complexity of the different hand joints and heterogeneity of OA pathology. Methods We used data from the Rotterdam Study (RSI, RSII and RSIII) to create three hand OA phenotypes based on clustering patterns of radiographic OA severity to increase power in our modest discovery genome-wide association studies in the RS (n=8700), and sought replication in an independent cohort, the Framingham Heart Study (n=1203). We used multiple approaches that leverage different levels of information and functional data to further investigate the underlying biological mechanisms and candidate genes for replicated loci. We also attempted to replicate known OA loci at other joint sites, including the hips and knees. Results We found two novel genome-wide significant loci for OA in the thumb joints. We identified WNT9A as a possible novel causal gene involved in OA pathogenesis. Furthermore, several previously identified genetic loci for OA seem to confer risk for OA across multiple joints: TGFa, RUNX2, COL27A1, ASTN2, IL11 and GDF5 loci. Conclusions We identified a robust novel genetic locus for hand OA on chromosome 1, of which WNT9A is the most likely causal gene. In addition, multiple genetic loci were identified to be associated with OA across multiple joints. Our study confirms the potential for novel insight into the genetic architecture of OA by using biologically meaningful stratified phenotypes.

Published
2021

50. 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, Fiona A., Pool, René, van Dongen, Jenny, Draisma, H. M., Jan Hottenga, Jouke, 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. Eka, Beekman, Marian, Slagboom, P. Eline, 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., ‘t Hart, L. M., van den Maagdenberg, A. M.J.M., van der Harst, P., van der Horst, I. C.C., van der Kallen, C. J.H., van Greevenbroek, M. M.J., van Spil, W. E., Wijmenga, C., Zwinderman, A. H., Zhernikova, A., Jukema, J. W., Mei, H., Slofstra, M., Swertz, M., van den Akker, E. B., Deelen, J., Reinders, M. J.T., Harms, Amy C., Hankemeier, Thomas, Bartels, Meike, Nivard, Michel G., Boomsma, Dorret I., Neurology, APH - Health Behaviors & Chronic Diseases, ACS - Heart failure & arrhythmias, Epidemiology and Data Science, General practice, APH - Methodology, APH - Mental Health, Psychiatry, Clinical chemistry, APH - Aging & Later Life, APH - Personalized Medicine, APH - Digital Health, and ACS - Diabetes & metabolism

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
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results