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1. Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX

Author

Kanis, J.A., Johansson, H., McCloskey, E.V., Liu, E., Åkesson, K.E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, C., Bischoff-Ferrari, H.A., Biver, E., Bruyère, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S.R., da Silva, J.A.P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J.M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.-C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R.J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M.K., Khosla, S., Kiel, D.P., Koh, W.-P., Koromani, F., Kotowicz, M.A., Kröger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellström, D., Merlijn, T., Nordström, A., Nordström, P., O’Neill, T.W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E.S., Pasco, J.A., Rivadeneira, F., Schott, A.-M., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M.A., Szulc, P., Tamaki, J., Torgerson, D.J., van Schoor, N.M., van Staa, T.P., Vila, J., Wareham, N.J., Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Vandenput, L., Harvey, N.C., Lorentzon, M., and Leslie, W.D.

Published
2023
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4. Within-Person Pain Variability and Mental Health in Older Adults With Osteoarthritis: An Analysis Across 6 European Cohorts

Author

Nikolaus, T., Denkinger, M., Peter, R., Herbolsheimer, F., Maggi, S., Zambon, S., Limongi, F., Noale, M., Siviero, P., Deeg, D.J.H., van der Pas, S., van Schoor, N.M., Schaap, L.A., Timmermans, E.J., Lips, P., Otero, Á., Castell, M.V., Sanchez-Martinez, M., Pedersen, N.L., Dennison, E.M., Cooper, C., Edwards, M.H., de Koning, Elisa J., Timmermans, Erik J., van Schoor, Natasja M., Stubbs, Brendon, van den Kommer, Tessa N., Dennison, Elaine M., Limongi, Federica, Castell, Maria Victoria, Edwards, Mark H., Queipo, Rocio, Cooper, Cyrus, Siviero, Paola, van der Pas, Suzan, Pedersen, Nancy L., Sánchez-Martínez, Mercedes, Deeg, Dorly J.H., and Denkinger, Michael D.

Published
2018
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8. Are higher antidepressant plasma concentrations associated with fall risk in older antidepressant users?

Author

Pronk, A.C., van Poelgeest, E.P., Seppala, L.J., Ploegmakers, K.J., Stricker, B.H., Swart, K.M.A., van Dijk, S.C., Oliai Araghi, S., de Groot, L.C.P.G.M., van Schoor, N.M., Mathôt, R.A.A., van der Velde, N., Pronk, A.C., van Poelgeest, E.P., Seppala, L.J., Ploegmakers, K.J., Stricker, B.H., Swart, K.M.A., van Dijk, S.C., Oliai Araghi, S., de Groot, L.C.P.G.M., van Schoor, N.M., Mathôt, R.A.A., and van der Velde, N.

Abstract

Antidepressants are well-established fall-risk increasing drugs (FRIDs) and therefore falls should be considered an important adverse drug event (ADE) of antidepressants. However, not all antidepressant users experience fall incidents and factors associated with increased fall risk among antidepressant users are incompletely understood. Our objective was to explore whether antidepressant plasma concentrations are associated with falls in older antidepressant users. Methods: For this study, we included antidepressant users of the multicenter B-PROOF study. Fall incidents were recorded prospectively using fall calendars. Antidepressant plasma concentrations were analyzed by Liquid chromatography-mass spectrometry (LC–MS) at baseline and at 2 years follow-up. The associations between the observed antidepressant concentration and fall risk were assessed using Cox proportional hazard and logistic regression models and adjusted for potential confounders. Results: In total 93 selective serotonin reuptake inhibitor (SSRI) and 41 antidepressant (TCA) users were identified. There was a significant association between baseline TCA plasma concentration and fall risk within users (HR 2.50, 95% CI 1.07–5.87, crude model). In the adjusted model, there were no significant associations between concentrations of SSRIs and fall risk. Conclusion: There might be an association between plasma concentrations of TCAs and the risk of falling in older users. However, these results needs to be interpreted with caution considering the small sample size and accompanying limitation of confinement to crude analyses. Therefore, these novel findings need to replicated in a larger cohort, preferably including adjustment for potential confounders and more frequent measures of plasma concentrations is needed.

Published
2023

12. B-vitamin levels and genetics of hyperhomocysteinemia are not associated with arterial stiffness

Author

van Dijk, S.C., Enneman, A.W., van Meurs, J., Swart, K.M.A., Ham, A.H., van Wijngaarden, J.P., Brouwer-Brolsma, E.M., van der Zwaluw, N.L., van Schoor, N.M., Dhonukshe-Rutten, R.A.M., de Groot, L.C.P.G.M., Lips, P., Uitterlinden, A.G., Blom, H., Geleijnse, J.M., Feskens, E., de Jongh, R.T., Smulders, Y.M., van den Meiracker, A.H., Mattace-Raso, F.U.S., and van der Velde, N.

Published
2014
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17. Update of the fracture risk prediction tool FRAX: A systematic review of potential cohorts and analysis plan

Author

Vandenput, Lisbeth, Johansson, H., McCloskey, E. V., Liu, E., Akesson, Kristina E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, Charlotte, Bischoff-Ferrari, H.A., Biver, E., Bruyère, Olivier, Cauley, J.A., Center, J.R., Chapulat, R., Christiansen, C., Cooper, Cyrus, Crandall, Carolyn J., Cummings, Steven, da Silva, J.A.P., Dawson-Hughes, Bess, Diez-Pérez, A., Dufour, Alyssa B., Eisman, J.A., Elders, Petra J.M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.C., Goldstein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, Rosemary J., Huisman, Martijn, Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M.K., Khosla, Sundeep, Kiel, D.P., Koh, W-P, Koromani, F., Kotowicz, M.A., Kroger, H., Kwok, T., Lamy, Olivier, Langhammer, Arnulf, Larijani, Bagher, Lippuner, Kurt, Mellström, D, Merlijn, Thomas, Nordstrom, A., Nordstrom, P., O'Neill, T.W., Obermayer-Piestch, B., Harvey, Nicholas, Kanis, J A., Ohlsson, C., Orwoll, E.S., Pasco, J.A., Rivadeneira, F., Schei, B., Schott, A.M., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M.A., Szulc, P., Tamaki, J., Torgerson, D.J., Van Schoor, N.M., van Staa, T.P., Vilas, J.C., Wareham, N.J, Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Lorentzon, M., and Leslie, W.D.

Abstract

Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Published
2022

18. Update of the fracture risk prediction tool FRAX : a systematic review of potential cohorts and analysis plan

Author

Vandenput, L., Johansson, H., McCloskey, E.V., Liu, E., Åkesson, K.E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, C., Bischoff-Ferrari, H.A., Biver, E., Bruyère, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S.R., da Silva, J.A.P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J.M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.-C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R.J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M.K., Khosla, S., Kiel, D.P., Koh, W.-P., Koromani, F., Kotowicz, M.A., Kröger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellström, D., Merlijn, T., Nordström, Annika, Nordström, Peter, O’Neill, T.W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E.S., Pasco, J.A., Rivadeneira, F., Schei, B., Schott, A.-M., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M.A., Szulc, P., Tamaki, J., Torgerson, D.J., van Schoor, N.M., van Staa, T.P., Vila, J., Wareham, N.J., Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Harvey, N.C., Lorentzon, M., Leslie, W.D., Kanis, J.A., Vandenput, L., Johansson, H., McCloskey, E.V., Liu, E., Åkesson, K.E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, C., Bischoff-Ferrari, H.A., Biver, E., Bruyère, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S.R., da Silva, J.A.P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J.M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.-C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R.J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M.K., Khosla, S., Kiel, D.P., Koh, W.-P., Koromani, F., Kotowicz, M.A., Kröger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellström, D., Merlijn, T., Nordström, Annika, Nordström, Peter, O’Neill, T.W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E.S., Pasco, J.A., Rivadeneira, F., Schei, B., Schott, A.-M., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M.A., Szulc, P., Tamaki, J., Torgerson, D.J., van Schoor, N.M., van Staa, T.P., Vila, J., Wareham, N.J., Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Harvey, N.C., Lorentzon, M., Leslie, W.D., and Kanis, J.A.

Abstract

Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of

Published
2022
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19. Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults

Author

Pronk, A.C., Seppala, L.J., Trajanoska, K., Stringa, N., van de Loo, B., de Groot, L.C.P.G.M., Koskeridis, F., van Schoor, N.M., Markozannes, G., Ntzani, E., Uitterlinden, A.G., Rivadeneira, F., Stricker, B.H., van der Velde, N., Pronk, A.C., Seppala, L.J., Trajanoska, K., Stringa, N., van de Loo, B., de Groot, L.C.P.G.M., Koskeridis, F., van Schoor, N.M., Markozannes, G., Ntzani, E., Uitterlinden, A.G., Rivadeneira, F., Stricker, B.H., and van der Velde, N.

Abstract

Background Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users. Methods The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated. Results In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26–0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17–3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07–2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05–3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01–1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased r

Published
2022

20. Homocysteine and the methylenetetrahydrofolate reductase 677C → T polymorphism in relation to muscle mass and strength, physical performance and postural sway

Author

Swart, K.M.A., Enneman, A.W., van Wijngaarden, J.P., van Dijk, S.C., Brouwer-Brolsma, E.M., Ham, A.C., Dhonukshe-Rutten, R.A.M., van der Velde, N., Brug, J., van Meurs, J.B.J., de Groot, L.C.P.G.M., Uitterlinden, A.G., Lips, P., and van Schoor, N.M.

Subjects
Aged -- Physiological aspects -- Food and nutrition, Muscle strength -- Research, Homocysteine -- Physiological aspects, Food/cooking/nutrition, Health
Abstract

BACKGROUND/OBJECTIVES: Elevated plasma homocysteine has been linked to reduced mobility and muscle functioning in the elderly. The relation of methylenetetrahydrofolate reductase (MTHFR) 677C → T polymorphism with these associations has not yet been studied. This study aimed to investigate (1) the association of plasma homocysteine and the MTHFR 677C → T polymorphism with muscle mass, handgrip strength, physical performance and postural sway; (2) the interaction between plasma homocysteine and the MTHFR 677C → T polymorphism. SUBJECTS/METHODS: Baseline data from the B-PROOF study (n = 2919, mean age = 74.1 ± 6.5) were used. Muscle mass was measured using dual X-ray absorptiometry, handgrip strength with a handheld dynamometer, and physical performance with walking-, chair stand- and balance tests. Postural sway was assessed on a force platform. The data were analyzed using regression analyses with plasma homocysteine levels in quartiles. RESULTS: There was a significant inverse association between plasma homocysteine and handgrip strength (quartile 4: regression coefficient B = - 1.14, 95% confidence interval (CI) = -1.96; -0.32) and physical performance score (quartile 3: B = - 0.53, 95% CI = -0.95; -0.10 and quartile 4: -0.94; 95% CI = -1.40; -0.48) in women only, independent of serum vitamin B12 and folic acid. No association was observed between the MTHFR 677C [right arrow] T polymorphism and the outcomes. High plasma homocysteine in the 677CC and 677CT genotypes, but not in the 677TT genotype, was associated with lower physical performance. CONCLUSIONS: Elevated plasma homocysteine concentrations are associated with reduced physical performance and muscle strength in older women. There is an urgent need for randomized controlled trials to examine whether lowering homocysteine levels might delay physical decline. European Journal of Clinical Nutrition (2013) 67, 743-748; doi: 10.1038/ejcn.2013.97; published online 22 May 2013 Keywords: homocysteine; MTHFR 677C → T polymorphism; mobility limitation; muscle strength; aged, INTRODUCTION Muscle tissue is progressively lost with aging, contributing to a decline in muscle strength. Muscle weakness and loss of muscle strength are risk factors of reduced physical functioning, increased [...]

Published
2013
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21. Homocysteine and the risk of nursing home admission and mortality in older persons

Author

Swart, K.M.A., van Schoor, N.M., Blom, H.J., Smulders, Y.M., and Lips, P.

Subjects
Aged -- Health aspects, Mortality -- Research -- Netherlands, Homocysteine -- Physiological aspects -- Research, Food/cooking/nutrition, Health
Abstract

Background/Objectives: This study aimed to investigate whether higher homocysteine and lower vitamin B12 concentrations increase the risk of future nursing home (NH) admission and all-cause mortality in independently living older persons. Subjects/Methods: In total, 1117 independently living participants (mean age = 75.1, s.d. = 6.4) were included in this prospective sub-study of the Longitudinal Aging Study Amsterdam. EDTA plasma samples, collected in 1995-1996, were analysed for total homocysteine (umol/l). Time to NH admission was assessed using a follow-up until 2002-2003. In addition, we studied mortality until 1 June 2007. Cox proportional hazards models were used to examine the association between homocysteine in quartiles and risk of NH admission and mortality. Results: During follow-up, 126 persons (11.3%) were admitted to NHs, and 513 persons (45.9%) deceased. In men, no significant associations were observed. In women, after adjustment for confounding, the highest quartile of homocysteine was associated with a significantly higher risk of NH admission compared with the first quartile (hazard ratio (HR) = 2.97, 95% confidence interval (CI) = 1.36-6.49). Both women in the third and the fourth quartile of homocysteine had a significantly higher mortality risk (HR = 1.70, 95% CI = 1.08-2.65 and HR = 1.91, 95% CI = 1.22-3.00, respectively) compared with the first quartile. Vitamin B12 was not related to an increased risk of NH admission and mortality. Conclusions: Elevated plasma homocysteine is associated with an increased risk of NH admission and mortality in older women, but not in older men. European Journal of Clinical Nutrition (2012) 66, 188-195; doi: 10.1038/ejcn.2011.186; published online 9 November 2011 Keywords: homocysteine; vitamin B12; nursing homes; mortality; aged, Introduction In the older population, elevated plasma homocysteine concentrations are present in 30-50% of the persons (de Bree et al., 2005). Plasma homocysteine concentrations are influenced by a complex interaction [...]

Published
2012
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22. Cross-sectional and longitudinal association between homocysteine, vitamin B12 and physical performance in older persons

Author

van Schoor, N.M., Swart, K.M.A., Pluijm, S.M.F., Visser, M., Simsek, S., Smulders, Y., and Lips, P.

Subjects
Aging -- Research, Vitamin B12 -- Physiological aspects -- Research, Homocysteine -- Physiological aspects -- Research, Middle aged women -- Health aspects, Food/cooking/nutrition, Health
Abstract

Background/Objectives: Decreases in physical performance are associated with multiple negative health outcomes. The objective of this study was to examine whether high plasma homocysteine and low serum vitamin B12 are independent risk factors for lower physical performance, both cross-sectionally and longitudinally. Subjects/Methods: This study was performed in persons aged ≥ 65 years of the LASA (Longitudinal Aging Study Amsterdam), an ongoing cohort study. Blood was collected in 1995/1996 (n = 1352). Physical performance was assessed in 1995/1996 and in 1998/1999 using three tests: the walking test, the chair stands test and the tandem stand (n = 901-1155). Results: After adjustment for confounding, women in the highest quartile of homocysteine had a significantly lower physical performance than did those in the lowest quartile in the cross-sectional analyses (β = -0.93, s.e. = 0.34, P Conclusions: High plasma homocysteine is an independent risk factor for lower physical performance in older women. The association between vitamin B12 and physical performance is less clear. European Journal of Clinical Nutrition (2012) 66, 174-181; doi: 10.1038/ejcn.2011.151; published online 24 August 2011 Keywords: homocysteine; older people; physical performance; vitamin B12, Introduction Homocysteine levels increase and vitamin B12 levels decrease with aging (Jacques et al., 1999; Refsum et al., 2004; Allen, 2009). In the LASA (Longitudinal Aging Study Amsterdam), a representative [...]

Published
2012
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24. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. 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Costantini, E. Vardy, E.R.L.C. Piras, F. Roveta, F. Piras, F. Prestia, F.A. Assogna, F. Salani, F. Sala, G. Lacidogna, G. Novack, G. Wilcock, G. Thonberg, H. Kölsch, H. Weber, H. Boecker, H. Etchepareborda, I. Piaceri, I. Tuomilehto, J. Lindström, J. Laczo, J. Johnston, J. Deleuze, J.-F. Harris, J. Schott, J.M. Priller, J. Bacha, J.I. Snowden, J. Lisso, J. Mihova, K.Y. Traykov, L. Morelli, L. Brusco, L.I. Rainer, M. Takalo, M. Bjerke, M. Del Zompo, M. Serpente, M. Sanchez Abalos, M. Rios, M. Peltonen, M. Herrman, M.J. Kosmidis, M.H. Kohler, M. Rojo, M. Jones, M. Orsini, M. Medel, N. Olivar, N. Fox, N.C. Salvadori, N. Hooper, N.M. Galeano, P. Solis, P. Bastiani, P. Mecocci, P. Passmore, P. Heun, R. Antikainen, R. Olaso, R. Perneczky, R. Germani, S. López-García, S. Love, S. Mehrabian, S. Bagnoli, S. Kochen, S. Andreoni, S. Teipel, S. Todd, S. Pickering-Brown, S. Natunen, T. Tegos, T. Laatikainen, T. Strandberg, T. Polvikoski, T.M. Matoska, V. Ciullo, V. Cores, V. Solfrizzi, V. 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Franco-Macías, E. Frank-García, A. García-Alberca, J.M. Garcia Madrona, S. Garcia-Ribas, G. Gómez-Garre, P. Hernández, I. Hevilla, S. Jesús, S. Labrador Espinosa, M.A. Lage, C. Legaz, A. Lleó, A. Lopez de Munain, A. López-García, S. Macias-García, D. Manzanares, S. Marín, M. Marín-Muñoz, J. Marín, T. Marquié, M. Martín Montes, A. Martínez, B. Martínez, C. Martínez, V. Martínez-Lage Álvarez, P. Medina, M. Mendioroz Iriarte, M. Mir, P. Molinuevo, J.L. Pastor, P. Pérez Tur, J. Periñán-Tocino, T. Pineda-Sanchez, R. Piñol-Ripoll, G. Rábano, A. Real de Asúa, D. Rodrigo, S. Rodríguez-Rodríguez, E. Royo, J.L. Ruiz, A. Sanchez del Valle Díaz, R. Sánchez-Juan, P. Sastre, I. Valero, S. Vicente, M.P. Vigo-Ortega, R. Vivancos, L. Macleod, C. McCracken, C. Brayne, C. Bresner, C. Grozeva, D. Bellou, E. Sommerville, E.W. Matthews, F. Leonenko, G. Menzies, G. Windle, G. Harwood, J. Phillips, J. Bennett, K. Luckuck, L. Clare, L. Woods, R. Saad, S. Burholt, V. Jansen, I.E. Rongve, A. Kehoe, P.G. Garcia-Ribas, G. Sánchez-Juan, P. Pastor, P. Pérez-Tur, J. Piñol-Ripoll, G. Lopez de Munain, A. García-Alberca, J.M. Bullido, M.J. Álvarez, V. Lleó, A. Real, L.M. Scheltens, P. Holstege, H. Marquié, M. Sáez, M.E. Carracedo, Á. Amouyel, P. Schellenberg, G.D. Williams, J. Seshadri, S. van Duijn, C.M. Mather, K.A. Sánchez-Valle, R. Serrano-Ríos, M. Orellana, A. Tárraga, L. Blennow, K. Huisman, M. Andreassen, O.A. Posthuma, D. Clarimón, J. Boada, M. van der Flier, W.M. Ramirez, A. Lambert, J.-C. van der Lee, S.J. Ruiz, A. EADB contributors The GR@ACE study group DEGESCO consortium IGAP (ADGC, CHARGE, EADI, GERAD) PGC-ALZ consortia

Abstract

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).

Published
2021

25. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author

Iurilli, M.L.C. Zhou, B. Bennett, J.E. Carrillo-Larco, R.M. Sophiea, M.K. Rodriguez-Martinez, A. Bixby, H. Solomon, B.D. Taddei, C. Danaei, G. Di Cesare, M. Stevens, G.A. Riley, L.M. Savin, S. Cowan, M.J. Bovet, P. Damasceno, A. Chirita-Emandi, A. Hayes, A.J. Ikeda, N. Jackson, R.T. Khang, Y.-H. Laxmaiah, A. Liu, J. Miranda, J.J. Saidi, O. Sebert, S. Sorić, M. Starc, G. Gregg, E.W. Abarca-Gómez, L. Abdeen, Z.A. Abdrakhmanova, S. Ghaffar, S.A. Rahim, H.F.A. Abu-Rmeileh, N.M. Garba, J.A. Acosta-Cazares, B. Adams, R.J. Aekplakorn, W. Afsana, K. Afzal, S. Agdeppa, I.A. Aghazadeh-Attari, J. Aguilar-Salinas, C.A. Agyemang, C. Ahmad, M.H. Ahmad, N.A. Ahmadi, A. Ahmadi, N. Ahmed, S.H. Ahrens, W. Aitmurzaeva, G. Ajlouni, K. Al-Hazzaa, H.M. Al-Lahou, B. Al-Raddadi, R. Alarouj, M. AlBuhairan, F. AlDhukair, S. Ali, M.M. Alkandari, A. Alkerwi, A. Allin, K. Alvarez-Pedrerol, M. Aly, E. Amarapurkar, D.N. Amiri, P. Amougou, N. Amouyel, P. Andersen, L.B. Anderssen, S.A. Ängquist, L. Anjana, R.M. Ansari-Moghaddam, A. Aounallah-Skhiri, H. Araújo, J. Ariansen, I. Aris, T. Arku, R.E. Arlappa, N. Aryal, K.K. Aspelund, T. Assah, F.K. Assunção, M.C.F. Aung, M.S. Auvinen, J. Mária Avdicová Avi, S. Azevedo, A. Azimi-Nezhad, M. Azizi, F. Azmin, M. Babu, B.V. Bæksgaard Jørgensen, M. Baharudin, A. Bahijri, S. Baker, J.L. Balakrishna, N. Bamoshmoosh, M. Banach, M. Bandosz, P. Banegas, J.R. Baran, J. Barbagallo, C.M. Barceló, A. Barkat, A. Barros, A.J.D. Barros, M.V.G. Basit, A. Bastos, J.L.D. Bata, I. Batieha, A.M. Batista, R.L. Battakova, Z. Batyrbek, A. Baur, L.A. Beaglehole, R. Bel-Serrat, S. Belavendra, A. Romdhane, H.B. Benedics, J. Benet, M. Bergh, I.H. Berkinbayev, S. Bernabe-Ortiz, A. Bernotiene, G. Bettiol, H. Bezerra, J. Bhagyalaxmi, A. Bharadwaj, S. Bhargava, S.K. Bhutta, Z.A. Bi, H. Bi, Y. Bia, D. Lele, E.C.B. Bikbov, M.M. Bista, B. Bjelica, D.J. Bjerregaard, P. Bjertness, E. Bjertness, M.B. Björkelund, C. Bloch, K.V. Blokstra, A. Bo, S. Bobak, M. Boddy, L.M. Boehm, B.O. 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Gurzkowska, B. Gutiérrez-González, E. Gutierrez, L. Gutzwiller, F. Ha, S. Hadaegh, F. Hadjigeorgiou, C.A. Haghshenas, R. Hakimi, H. Halkjær, J. Hambleton, I.R. Hamzeh, B. Hange, D. Hanif, A.A.M. Hantunen, S. Hao, J. Kumar, R.H. Hashemi-Shahri, S.M. Hassapidou, M. Hata, J. Haugsgjerd, T. He, J. He, Y. He, Y. Heidinger-Felso, R. Heinen, M. Hejgaard, T. Hendriks, M.E. dos Santos Henrique, R. Henriques, A. Cadena, L.H. Herrala, S. Herrera, V.M. Herter-Aeberli, I. Heshmat, R. Hill, A.G. Ho, S.Y. Ho, S.C. Hobbs, M. Holdsworth, M. Homayounfar, R. Homs, C. Hopman, W.M. Horimoto, A.R.V.R. Hormiga, C.M. Horta, B.L. Houti, L. Howitt, C. Htay, T.T. Htet, A.S. Htike, M.M.T. Hu, Y. Huerta, J.M. Huhtaniemi, I.T. Huiart, L. Petrescu, C.H. Huisman, M. Husseini, A. Huu, C.N. Huybrechts, I. Hwalla, N. Hyska, J. Iacoviello, L. Ibarluzea, J.M. Ibrahim, M.M. Wong, N.I. Ikram, M.A. Iotova, V. Irazola, V.E. Ishida, T. Islam, M. Islam, S.M.S. Iwasaki, M. Jacobs, J.M. Jaddou, H.Y. Jafar, T. James, K. Jamil, K.M. Jamrozik, K. Janszky, I. Janus, E. Jarani, J. Jarvelin, M.-R. Jasienska, G. Jelakovic, A. Jelakovic, B. Jennings, G. Jha, A.K. Jiang, C.Q. Jimenez, R.O. Jöckel, K.-H. Joffres, M. Johansson, M. Jokelainen, J.J. Jonas, J.B. Jonnagaddala, J. Jørgensen, T. Joshi, P. Joukar, F. Jovic, D.P. Jóźwiak, J.J. Juolevi, A. Jurak, G. Simina, I.J. Juresa, V. Kaaks, R. Kaducu, F.O. Kafatos, A. Kajantie, E.O. Kalmatayeva, Z. Kalter-Leibovici, O. Kameli, Y. Kampmann, F.B. Kanala, K.R. Kannan, S. Kapantais, E. Karakosta, A. Kårhus, L.L. Karki, K.B. Katibeh, M. Katz, J. Katzmarzyk, P.T. Kauhanen, J. Kaur, P. Kavousi, M. Kazakbaeva, G.M. Keil, U. Boker, L.K. Keinänen-Kiukaanniemi, S. Kelishadi, R. Kelleher, C. Kemper, H.C.G. Kengne, A.P. Keramati, M. Kerimkulova, A. Kersting, M. Key, T. Khader, Y.S. Khalili, D. Khaw, K.-T. Kheiri, B. Kheradmand, M. Khosravi, A. Khouw, I.M.S.L. Kiechl-Kohlendorfer, U. Kiechl, S. Killewo, J. Kim, D.W. Kim, H.C. Kim, J. Kindblom, J.M. Klakk, H. Klimek, M. 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Tolonen, H.K. Tolstrup, J.S. Topbas, M. Topór-Madry, R. Torheim, L.E. Tormo, M.J. Tornaritis, M.J. Torrent, M. Torres-Collado, L. Toselli, S. Touloumi, G. Traissac, P. Tran, T.T.-H. Trichopoulos, D. Trichopoulou, A. Trinh, D.T.H. Trivedi, A. Tshepo, L. Tsigga, M. Tsugane, S. Tuliakova, A.M. Tulloch-Reid, M.K. Tullu, F. Tuomainen, T.-P. Tuomilehto, J. Turley, M.L. Twig, G. Tynelius, P. Tzotzas, T. Tzourio, C. Ueda, P. Ugel, E. Ukoli, F.A.M. Ulmer, H. Unal, B. Usupova, Z. Uusitalo, H.M.T. Uysal, N. Vaitkeviciute, J. Valdivia, G. Vale, S. Valvi, D. van Dam, R.M. Van der Heyden, J. van der Schouw, Y.T. Van Herck, K. Van Minh, H. Van Schoor, N.M. van Valkengoed, I.G.M. Vanderschueren, D. Vanuzzo, D. Varbo, A. Varela-Moreiras, G. Varona-Pérez, P. Vasan, S.K. Vega, T. Veidebaum, T. Velasquez-Melendez, G. Velika, B. Veronesi, G. Verschuren, W.M.M. Victora, C.G. Viegi, G. Viet, L. Villalpando, S. Vineis, P. Vioque, J. Virtanen, J.K. Visser, M. Visvikis-Siest, S. Viswanathan, B. Vladulescu, M. Vlasoff, T. Vocanec, D. Vollenweider, P. Völzke, H. Voutilainen, A. Voutilainen, S. Vrijheid, M. Vrijkotte, T.G.M. Wade, A.N. Wagner, A. Waldhör, T. Walton, J. Wambiya, E.O.A. Bebakar, A.M.W. Mohamud, W.N.W. de Souza Wanderley Júnior, R. Wang, M.-D. Wang, N. Wang, Q. Wang, X. Wang, Y.X. Wang, Y.-W. Wannamethee, S.G. Wareham, N. Weber, A. Wedderkopp, N. Weerasekera, D. Weghuber, D. Wei, W. Weres, A. Werner, B. Whincup, P.H. Widhalm, K. Widyahening, I.S. Wiecek, A. Wilks, R.J. Willeit, J. Willeit, P. Williams, J. Wilsgaard, T. Wojtyniak, B. Wong-McClure, R.A. Wong, A. Wong, J.E. Wong, T.Y. Woo, J. Woodward, M. Wu, F.C. Wu, J. Wu, L.J. Wu, S. Xu, H. Xu, L. Yaacob, N.A. Yamborisut, U. Yan, W. Yang, L. Yang, X. Yang, Y. Yardim, N. Yaseri, M. Yasuharu, T. Ye, X. Yiallouros, P.K. Yoosefi, M. Yoshihara, A. You, Q.S. You, S.-L. Younger-Coleman, N.O. Yusof, S.M. Yusoff, A.F. Zaccagni, L. Zafiropulos, V. Zainuddin, A.A. Zakavi, S.R. Zamani, F. Zambon, S. Zampelas, A. Zamrazilová, H. Zapata, M.E. Zargar, A.H. Zaw, K.K. Zdrojewski, T. Zejglicova, K. Vrkic, T.Z. Zeng, Y. Zhang, L. Zhang, Z.-Y. Zhao, D. Zhao, M.-H. Zhao, W. Zhen, S. Zheng, W. Zheng, Y. Zholdin, B. Zhou, M. Zhu, D. Zins, M. Zitt, E. Zocalo, Y. Cisneros, J.Z. Zuziak, M. Ezzati, M. Filippi, S. NCD Risk Factor Collaboration (NCD-RisC)

Subjects
nutritional and metabolic diseases, sense organs, skin and connective tissue diseases
Abstract

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions. © Copyright.

Published
2021

26. Genetics Contributes to Concomitant Pathology and Clinical Presentation in Dementia with Lewy Bodies

Author

van der Lee, S.J. (author), van Steenoven, Inger (author), van de Beek, Marleen (author), Tesi, N. (author), Jansen, Iris E. (author), van Schoor, N.M. (author), Reinders, M.J.T. (author), Huisman, Martijn (author), Scheltens, Philip (author), van der Lee, S.J. (author), van Steenoven, Inger (author), van de Beek, Marleen (author), Tesi, N. (author), Jansen, Iris E. (author), van Schoor, N.M. (author), Reinders, M.J.T. (author), Huisman, Martijn (author), and Scheltens, Philip (author)

Abstract

Background: Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity. Objective: We tested if genetic variants in part explain the heterogeneity in DLB. Methods: We tested the effects of variants previously associated with DLB (near APOE, GBA, and SNCA) and polygenic risk scores for Alzheimer's disease (AD-PRS) and Parkinson's disease (PD-PRS). We studied 190 probable DLB patients from the Alzheimer's dementia cohort and compared them to 2,552 control subjects. The p-tau/Aβ1-42 ratio in cerebrospinal fluid was used as in vivo proxy to separate DLB cases into DLB with concomitant AD pathology (DLB-AD) or DLB without AD (DLB-pure). We studied the clinical measures age, Mini-Mental State Examination (MMSE), and the presence of core symptoms at diagnosis and disease duration. Results: We found that all studied genetic factors significantly associated with DLB risk (all-DLB). Second, we stratified the DLB patients by the presence of concomitant AD pathology and found that APOE ϵ4 and the AD-PRS associated specifically with DLB-AD, but less with DLB-pure. In addition, the GBA p.E365K variant showed strong associated with DLB-pure and less with DLB-AD. Last, we studied the clinical measures and found that APOE ϵ4 associated with reduced MMSE, higher odds to have fluctuations and a shorter disease duration. In addition, the GBA p.E365K variant reduced the age at onset by 5.7 years, but the other variants and the PRS did not associate with clinical features. Conclusion: These finding increase our understanding of the pathological and clinical heterogeneity in DLB., Pattern Recognition and Bioinformatics

Published
2021
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27. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I.E., Pedersen, N.L., Stringa, N., Zettergren, A., Hernández, I., Montrreal, L., Antúnez, C., Antonell, A., Tankard, R.M., Bis, J.C., Sims, R., Bellenguez, C., Quintela, I., González-Perez, A., Calero, M., Franco-Macías, E., Macías, J., Blesa, R., Cervera-Carles, L., Menéndez-González, M., Frank-García, A., Royo, J.L., Moreno, F., Huerto Vilas, R., Baquero, M., Diez-Fairen, M., Lage, C., García-Madrona, S., García-González, P., Alarcón-Martín, E., Valero, S., Sotolongo-Grau, O., Ullgren, A., Naj, A.C., Lemstra, A.W., Benaque, A., Pérez-Cordón, A., Benussi, A., Rábano, A., Padovani, A., Squassina, A., de Mendonça, A., Arias Pastor, A., Kok, A.A.L., Meggy, A., Pastor, A.B., Espinosa, A., Corma-Gómez, A., Martín Montes, A., Sanabria, Á., DeStefano, A.L., Schneider, A., Haapasalo, A., Kinhult Ståhlbom, A., Tybjærg-Hansen, A., Hartmann, A.M., Spottke, A., Corbatón-Anchuelo, A., Rongve, A., Borroni, B., Arosio, B., Nacmias, B., Nordestgaard, B.G., Kunkle, B.W., Charbonnier, C., Abdelnour, C., Masullo, C., Martínez Rodríguez, C., Muñoz-Fernandez, C., Dufouil, C., Graff, C., Ferreira, C.B., Chillotti, C., Reynolds, C.A., Fenoglio, C., Van Broeckhoven, C., Clark, C., Pisanu, C., Satizabal, C.L., Holmes, C., Buiza-Rueda, D., Aarsland, D., Rujescu, D., Alcolea, D., Galimberti, D., Wallon, D., Seripa, D., Grünblatt, E., Dardiotis, E., Düzel, E., Scarpini, E., Conti, E., Rubino, E., Gelpi, E., Rodriguez-Rodriguez, E., Duron, E., Boerwinkle, E., Ferri, E., Tagliavini, F., Küçükali, F., Pasquier, F., Sanchez-Garcia, F., Mangialasche, F., Jessen, F., Nicolas, G., Selbæk, G., Ortega, G., Chêne, G., Hadjigeorgiou, G., Rossi, G, Spalletta, G., Giaccone, G., Grande, G., Binetti, G., Papenberg, G., Hampel, H., Bailly, H., Zetterberg, H., Soininen, H., Karlsson, I.K., Alvarez, I., Appollonio, I., Giegling, I., Skoog, I., Saltvedt, I., Rainero, I., Rosas Allende, I., Hort, J., Diehl-Schmid, J., Van Dongen, J., Vidal, J-S, Lehtisalo, J., Wiltfang, J., Thomassen, J.Q., Kornhuber, J., Haines, J.L., Vogelgsang, J., Pineda, J.A., Fortea, J., Popp, J., Deckert, J., Buerger, K., Morgan, K., Fließbach, K., Sleegers, K., Molina-Porcel, L., Kilander, L., Weinhold, L., Farrer, L.A., Wang, L-S, Kleineidam, L., Farotti, L., Parnetti, L., Tremolizzo, L., Hausner, L., Benussi, L., Froelich, L., Ikram, M.A., Deniz-Naranjo, M.C., Tsolaki, M., Rosende-Roca, M., Löwenmark, M., Hulsman, M., Spallazzi, M., Pericak-Vance, M.A., Esiri, M., Bernal Sánchez-Arjona, M., Dalmasso, M.C., Martínez-Larrad, M.T., Arcaro, M., Nöthen, M.M., Fernández-Fuertes, M., Dichgans, M., Ingelsson, M., Herrmann, M.J., Scherer, M., Vyhnalek, M., Kosmidis, M.H., Yannakoulia, M., Schmid, M., Ewers, M., Heneka, M.T., Wagner, M., Scamosci, M., Kivipelto, M., Hiltunen, M., Zulaica, M., Alegret, M., Fornage, M., Roberto, N., van Schoor, N.M., Seidu, N.M., Banaj, N., Armstrong, N.J., Scarmeas, N., Scherbaum, N., Goldhardt, O., Hanon, O., Peters, O., Skrobot, O.A., Quenez, O., Lerch, O., Bossù, P., Caffarra, P., Dionigi Rossi, P., Sakka, P., Hoffmann, P., Holmans, P.A., Fischer, P., Riederer, P., Yang, Q., Marshall, R., Kalaria, R.N., Mayeux, R., Vandenberghe, R., Cecchetti, R., Ghidoni, R., Frikke-Schmidt, R., Sorbi, S., Hägg, S., Engelborghs, S., Helisalmi, S., Botne Sando, S., Kern, S., Archetti, S., Boschi, S., Fostinelli, S., Gil, S., Mendoza, S., Mead, S., Ciccone, S., Djurovic, S., Heilmann-Heimbach, S., Riedel-Heller, S., Kuulasmaa, T., del Ser, T., Lebouvier, T., Polak, T., Ngandu, T., Grimmer, T., Bessi, V., Escott-Price, V., Giedraitis, V., Deramecourt, V., Maier, W., Jian, X., Pijnenburg, Y.A.L., Smith, A.D., Saenz, A., Bizzarro, A., Lauria, A., Vacca, A., Solomon, A., Anastasiou, A., Richardson, A., Boland, A., Koivisto, A., Daniele, A., Greco, A., Marianthi, A., McGuinness, B., Fin, B., Ferrari, Ca., Custodero, C., Ferrarese, C., Ingino, C., Mangone, C., Reyes Toso, C., Martinez, C., Cuesta, C., Muchnik, C., Joachim, C., Ortiz, C., Besse, C., Johansson, C., Zoia, C.P., Laske, C., Anastasiou, C., Palacio, D.L., Politis, D.G., Janowitz, D., Craig, D., Mann, D.M., Neary, D., Jürgen, D., Daian, D., Belezhanska, D., Kohler, E., Castaño, E.M., Koutsouraki, E., Chipi, E., De Roeck, E., Costantini, E., Vardy, E.R.L.C., Piras, F., Roveta, F., Prestia, F.A., Assogna, F., Salani, F., Sala, G., Lacidogna, G., Novack, G., Wilcock, G., Thonberg, H., Kölsch, H., Weber, H., Boecker, H., Etchepareborda, I., Piaceri, I., Tuomilehto, J., Lindström, J., Laczo, J., Johnston, J., Deleuze, J-F, Harris, J., Schott, J.M., Priller, J., Bacha, J.I., Snowden, J., Lisso, J., Mihova, K.Y., Traykov, L., Morelli, L., Brusco, L.I., Rainer, M., Takalo, M., Bjerke, M., Del Zompo, M., Serpente, M., Sanchez Abalos, M., Rios, M., Peltonen, M., Herrman, M.J., Kohler, M., Rojo, M., Jones, M., Orsini, M., Medel, N., Olivar, N., Fox, N.C., Salvadori, N., Hooper, N.M., Galeano, P., Solis, P., Bastiani, P., Mecocci, P., Passmore, P., Heun, R., Antikainen, R., Olaso, R., Perneczky, R., Germani, S., López-García, S., Love, S., Mehrabian, S., Bagnoli, S., Kochen, S., Andreoni, S., Teipel, S., Todd, S., Pickering-Brown, S., Natunen, T., Tegos, T., Laatikainen, T., Strandberg, T., Polvikoski, T.M., Matoska, V., Ciullo, V., Cores, V., Solfrizzi, V., Lisetti, V., Sevillano, Z., Aguilera, N., Alarcon, E., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., Diego, S., Gailhajenet, A., Guitart, M., González-Pérez, A., Ibarria, M., Lafuente, A., Macias, J., Maroñas, O., Martín, E., Martínez, M. T., Marquié, M., Mauleón, A., Moreno, M., Orellana, A., Pancho, A., Pelejá, E., Pérez-Cordon, A., Pineda, J. A., Preckler, S., Real, L. M., Ruiz, A., Sáez, M. E., Sanabria, A., Serrano-Rios, M., Tárraga, L., Vargas, L., Adarmes-Gómez, A. D., Alonso, M. D., Álvarez, I., Álvarez, V., Amer-Ferrer, G., Antequera, M., Bernal, M., Bullido, M.J., Burguera, J.A., Carrillo, F., Carrión-Claro, M., Casajeros, M.J., Clarimón, J., Cruz-Gamero, J.M., de Pancorbo, M.M., Escuela, R., Garrote-Espina, L., García-Alberca, J.M., Garcia Madrona, S., Garcia-Ribas, G., Gómez-Garre, P., Hevilla, S., Jesús, S., Labrador Espinosa, M.A., Legaz, A., Lleó, A., Lopez de Munain, A., Macias-García, D., Manzanares, S., Marín, M., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Mir, P., Molinuevo, J.L., Pastor, P., Pérez Tur, J., Periñán-Tocino, T., Pineda-Sanchez, R., Piñol-Ripoll, G., Real de Asúa, D., Rodrigo, S., Rodríguez-Rodríguez, E., Sanchez del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M.P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, C., Bresner, C., Grozeva, D., Bellou, E., Sommerville, E.W., Matthews, F., Leonenko, G., Menzies, G., Windle, G., Harwood, J., Phillips, J., Bennett, K., Luckuck, L., Clare, L., Woods, R., Saad, S., Burholt, V., Kehoe, P.G., Pérez-Tur, J., Real, L.M., Scheltens, P., Holstege, H., Sáez, M.E., Carracedo, Á., Amouyel, P., Schellenberg, G.D., Williams, J., Seshadri, S., van Duijn, C.M., Mather, K.A., Sánchez-Valle, R., Serrano-Ríos, M., Blennow, K., Huisman, M., Andreassen, O.A., Posthuma, D., van der Flier, W.M., Ramirez, A., Lambert, J-C, van der Lee, S.J., de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I.E., Pedersen, N.L., Stringa, N., Zettergren, A., Hernández, I., Montrreal, L., Antúnez, C., Antonell, A., Tankard, R.M., Bis, J.C., Sims, R., Bellenguez, C., Quintela, I., González-Perez, A., Calero, M., Franco-Macías, E., Macías, J., Blesa, R., Cervera-Carles, L., Menéndez-González, M., Frank-García, A., Royo, J.L., Moreno, F., Huerto Vilas, R., Baquero, M., Diez-Fairen, M., Lage, C., García-Madrona, S., García-González, P., Alarcón-Martín, E., Valero, S., Sotolongo-Grau, O., Ullgren, A., Naj, A.C., Lemstra, A.W., Benaque, A., Pérez-Cordón, A., Benussi, A., Rábano, A., Padovani, A., Squassina, A., de Mendonça, A., Arias Pastor, A., Kok, A.A.L., Meggy, A., Pastor, A.B., Espinosa, A., Corma-Gómez, A., Martín Montes, A., Sanabria, Á., DeStefano, A.L., Schneider, A., Haapasalo, A., Kinhult Ståhlbom, A., Tybjærg-Hansen, A., Hartmann, A.M., Spottke, A., Corbatón-Anchuelo, A., Rongve, A., Borroni, B., Arosio, B., Nacmias, B., Nordestgaard, B.G., Kunkle, B.W., Charbonnier, C., Abdelnour, C., Masullo, C., Martínez Rodríguez, C., Muñoz-Fernandez, C., Dufouil, C., Graff, C., Ferreira, C.B., Chillotti, C., Reynolds, C.A., Fenoglio, C., Van Broeckhoven, C., Clark, C., Pisanu, C., Satizabal, C.L., Holmes, C., Buiza-Rueda, D., Aarsland, D., Rujescu, D., Alcolea, D., Galimberti, D., Wallon, D., Seripa, D., Grünblatt, E., Dardiotis, E., Düzel, E., Scarpini, E., Conti, E., Rubino, E., Gelpi, E., Rodriguez-Rodriguez, E., Duron, E., Boerwinkle, E., Ferri, E., Tagliavini, F., Küçükali, F., Pasquier, F., Sanchez-Garcia, F., Mangialasche, F., Jessen, F., Nicolas, G., Selbæk, G., Ortega, G., Chêne, G., Hadjigeorgiou, G., Rossi, G, Spalletta, G., Giaccone, G., Grande, G., Binetti, G., Papenberg, G., Hampel, H., Bailly, H., Zetterberg, H., Soininen, H., Karlsson, I.K., Alvarez, I., Appollonio, I., Giegling, I., Skoog, I., Saltvedt, I., Rainero, I., Rosas Allende, I., Hort, J., Diehl-Schmid, J., Van Dongen, J., Vidal, J-S, Lehtisalo, J., Wiltfang, J., Thomassen, J.Q., Kornhuber, J., Haines, J.L., Vogelgsang, J., Pineda, J.A., Fortea, J., Popp, J., Deckert, J., Buerger, K., Morgan, K., Fließbach, K., Sleegers, K., Molina-Porcel, L., Kilander, L., Weinhold, L., Farrer, L.A., Wang, L-S, Kleineidam, L., Farotti, L., Parnetti, L., Tremolizzo, L., Hausner, L., Benussi, L., Froelich, L., Ikram, M.A., Deniz-Naranjo, M.C., Tsolaki, M., Rosende-Roca, M., Löwenmark, M., Hulsman, M., Spallazzi, M., Pericak-Vance, M.A., Esiri, M., Bernal Sánchez-Arjona, M., Dalmasso, M.C., Martínez-Larrad, M.T., Arcaro, M., Nöthen, M.M., Fernández-Fuertes, M., Dichgans, M., Ingelsson, M., Herrmann, M.J., Scherer, M., Vyhnalek, M., Kosmidis, M.H., Yannakoulia, M., Schmid, M., Ewers, M., Heneka, M.T., Wagner, M., Scamosci, M., Kivipelto, M., Hiltunen, M., Zulaica, M., Alegret, M., Fornage, M., Roberto, N., van Schoor, N.M., Seidu, N.M., Banaj, N., Armstrong, N.J., Scarmeas, N., Scherbaum, N., Goldhardt, O., Hanon, O., Peters, O., Skrobot, O.A., Quenez, O., Lerch, O., Bossù, P., Caffarra, P., Dionigi Rossi, P., Sakka, P., Hoffmann, P., Holmans, P.A., Fischer, P., Riederer, P., Yang, Q., Marshall, R., Kalaria, R.N., Mayeux, R., Vandenberghe, R., Cecchetti, R., Ghidoni, R., Frikke-Schmidt, R., Sorbi, S., Hägg, S., Engelborghs, S., Helisalmi, S., Botne Sando, S., Kern, S., Archetti, S., Boschi, S., Fostinelli, S., Gil, S., Mendoza, S., Mead, S., Ciccone, S., Djurovic, S., Heilmann-Heimbach, S., Riedel-Heller, S., Kuulasmaa, T., del Ser, T., Lebouvier, T., Polak, T., Ngandu, T., Grimmer, T., Bessi, V., Escott-Price, V., Giedraitis, V., Deramecourt, V., Maier, W., Jian, X., Pijnenburg, Y.A.L., Smith, A.D., Saenz, A., Bizzarro, A., Lauria, A., Vacca, A., Solomon, A., Anastasiou, A., Richardson, A., Boland, A., Koivisto, A., Daniele, A., Greco, A., Marianthi, A., McGuinness, B., Fin, B., Ferrari, Ca., Custodero, C., Ferrarese, C., Ingino, C., Mangone, C., Reyes Toso, C., Martinez, C., Cuesta, C., Muchnik, C., Joachim, C., Ortiz, C., Besse, C., Johansson, C., Zoia, C.P., Laske, C., Anastasiou, C., Palacio, D.L., Politis, D.G., Janowitz, D., Craig, D., Mann, D.M., Neary, D., Jürgen, D., Daian, D., Belezhanska, D., Kohler, E., Castaño, E.M., Koutsouraki, E., Chipi, E., De Roeck, E., Costantini, E., Vardy, E.R.L.C., Piras, F., Roveta, F., Prestia, F.A., Assogna, F., Salani, F., Sala, G., Lacidogna, G., Novack, G., Wilcock, G., Thonberg, H., Kölsch, H., Weber, H., Boecker, H., Etchepareborda, I., Piaceri, I., Tuomilehto, J., Lindström, J., Laczo, J., Johnston, J., Deleuze, J-F, Harris, J., Schott, J.M., Priller, J., Bacha, J.I., Snowden, J., Lisso, J., Mihova, K.Y., Traykov, L., Morelli, L., Brusco, L.I., Rainer, M., Takalo, M., Bjerke, M., Del Zompo, M., Serpente, M., Sanchez Abalos, M., Rios, M., Peltonen, M., Herrman, M.J., Kohler, M., Rojo, M., Jones, M., Orsini, M., Medel, N., Olivar, N., Fox, N.C., Salvadori, N., Hooper, N.M., Galeano, P., Solis, P., Bastiani, P., Mecocci, P., Passmore, P., Heun, R., Antikainen, R., Olaso, R., Perneczky, R., Germani, S., López-García, S., Love, S., Mehrabian, S., Bagnoli, S., Kochen, S., Andreoni, S., Teipel, S., Todd, S., Pickering-Brown, S., Natunen, T., Tegos, T., Laatikainen, T., Strandberg, T., Polvikoski, T.M., Matoska, V., Ciullo, V., Cores, V., Solfrizzi, V., Lisetti, V., Sevillano, Z., Aguilera, N., Alarcon, E., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., Diego, S., Gailhajenet, A., Guitart, M., González-Pérez, A., Ibarria, M., Lafuente, A., Macias, J., Maroñas, O., Martín, E., Martínez, M. T., Marquié, M., Mauleón, A., Moreno, M., Orellana, A., Pancho, A., Pelejá, E., Pérez-Cordon, A., Pineda, J. A., Preckler, S., Real, L. M., Ruiz, A., Sáez, M. E., Sanabria, A., Serrano-Rios, M., Tárraga, L., Vargas, L., Adarmes-Gómez, A. D., Alonso, M. D., Álvarez, I., Álvarez, V., Amer-Ferrer, G., Antequera, M., Bernal, M., Bullido, M.J., Burguera, J.A., Carrillo, F., Carrión-Claro, M., Casajeros, M.J., Clarimón, J., Cruz-Gamero, J.M., de Pancorbo, M.M., Escuela, R., Garrote-Espina, L., García-Alberca, J.M., Garcia Madrona, S., Garcia-Ribas, G., Gómez-Garre, P., Hevilla, S., Jesús, S., Labrador Espinosa, M.A., Legaz, A., Lleó, A., Lopez de Munain, A., Macias-García, D., Manzanares, S., Marín, M., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Mir, P., Molinuevo, J.L., Pastor, P., Pérez Tur, J., Periñán-Tocino, T., Pineda-Sanchez, R., Piñol-Ripoll, G., Real de Asúa, D., Rodrigo, S., Rodríguez-Rodríguez, E., Sanchez del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M.P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, C., Bresner, C., Grozeva, D., Bellou, E., Sommerville, E.W., Matthews, F., Leonenko, G., Menzies, G., Windle, G., Harwood, J., Phillips, J., Bennett, K., Luckuck, L., Clare, L., Woods, R., Saad, S., Burholt, V., Kehoe, P.G., Pérez-Tur, J., Real, L.M., Scheltens, P., Holstege, H., Sáez, M.E., Carracedo, Á., Amouyel, P., Schellenberg, G.D., Williams, J., Seshadri, S., van Duijn, C.M., Mather, K.A., Sánchez-Valle, R., Serrano-Ríos, M., Blennow, K., Huisman, M., Andreassen, O.A., Posthuma, D., van der Flier, W.M., Ramirez, A., Lambert, J-C, and van der Lee, S.J.

Abstract

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

Published
2021

28. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

Tesi, N. (author), Stringa, N. (author), Hadjigeorgiou, G. (author), Hulsman, M. (author), van Schoor, N.M. (author), Ruiz, A. (author), Jansen, I.E. (author), Holstege, H. (author), van der Lee, S.J. (author), Tesi, N. (author), Stringa, N. (author), Hadjigeorgiou, G. (author), Hulsman, M. (author), van Schoor, N.M. (author), Ruiz, A. (author), Jansen, I.E. (author), Holstege, H. (author), and van der Lee, S.J. (author)

Abstract

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease., Pattern Recognition and Bioinformatics

Published
2021
Full Text
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29. Development of the Qualeffo-31, an osteoporosis-specific quality-of-life questionnaire

Author

van Schoor, N.M., Knol, D.L., Glas, C.A.W., Ostelo, R.W.J.G., Leplege, A., Cooper, C., Johnell, O., and Lips, P.

Subjects
Osteoporosis -- Causes of, Osteoporosis -- Care and treatment, Osteoporosis -- Case studies, Quality of life -- Reports, Questionnaires -- Usage, Spinal cord injuries -- Risk factors, Spinal cord injuries -- Care and treatment, Health
Published
2006

32. The effect of high-intensity resistance training and vitamin d supplementation on muscle strength in patients with knee osteoarthritis: a randomized controlled trial

Author

de Zwart, A.H., primary, Dekker, J., additional, Roorda, L.D., additional, van der Esch, M., additional, Lips, P., additional, van Schoor, N.M., additional, Heijboer, A.C., additional, Turkstra, F., additional, Gerritsen, M., additional, Häkkinen, A., additional, Bennell, K., additional, Steultjens, M., additional, Lems, W.F., additional, and van der Leeden, M., additional

Published
2020
Full Text
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33. Immune response and endocytosis pathways are associated with the resilience against Alzheimer’s disease

Author

Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, N.M. (author), Scheltens, Philip (author), van der Flier, Wiesje M. (author), Huisman, Martijn (author), Reinders, M.J.T. (author), Holstege, H. (author), Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, N.M. (author), Scheltens, Philip (author), van der Flier, Wiesje M. (author), Huisman, Martijn (author), Reinders, M.J.T. (author), and Holstege, H. (author)

Abstract

Developing Alzheimer’s disease (AD) is influenced by multiple genetic variants that are involved in five major AD-pathways. Per individual, these pathways may differentially contribute to the modification of the AD-risk. The pathways involved in the resilience against AD have thus far been poorly addressed. Here, we investigated to what extent each molecular mechanism associates with (i) the increased risk of AD and (ii) the resilience against AD until extreme old age, by comparing pathway-specific polygenic risk scores (pathway-PRS). We used 29 genetic variants associated with AD to develop pathway-PRS for five major pathways involved in AD. We developed an integrative framework that allows multiple genes to associate with a variant, and multiple pathways to associate with a gene. We studied pathway-PRS in the Amsterdam Dementia Cohort of well-phenotyped AD patients (N = 1895), Dutch population controls from the Longitudinal Aging Study Amsterdam (N = 1654) and our unique 100-plus Study cohort of cognitively healthy centenarians who avoided AD (N = 293). Last, we estimated the contribution of each pathway to the genetic risk of AD in the general population. All pathway-PRS significantly associated with increased AD-risk and (in the opposite direction) with resilience against AD (except for angiogenesis, p < 0.05). The pathway that contributed most to the overall modulation of AD-risk was β-amyloid metabolism (29.6%), which was driven mainly by APOE-variants. After excluding APOE variants, all pathway-PRS associated with increased AD-risk (except for angiogenesis, p < 0.05), while specifically immune response (p = 0.003) and endocytosis (p = 0.0003) associated with resilience against AD. Indeed, the variants in these latter two pathways became the main contributors to the overall modulation of genetic risk of AD (45.5% and 19.2%, respectively). The genetic variants associated with the resilience against AD indicate which pathways are involved with maintaine, Pattern Recognition and Bioinformatics, Intelligent Systems

Published
2020
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34. Within-person pain variability and mental health in older adults with osteoarthritis: An analysis across six European Cohorts

Author

de Koning, E.J., Timmermans, E.J., Van Schoor, N.M., Stubbs, B., van den Kommer, T.N., Dennison, E.M., Limongi, F., Castell, M.V., Edwards, M.H., Queipo, R., Cooper, C., Siviero, P., van der Pas, S., Pedersen, N.L., Sanchez-Martinez, M., Deeg, D.J.H., and Denkinger, M.D.

Abstract

Pain is a key symptom of Osteoarthritis (OA) and has been linked to poor mental health. Pain fluctuates over time within individuals, but a paucity of studies have considered day-to-day fluctuations of joint pain in relation to affective symptoms in older persons with OA. This study investigated the relationship of both pain severity and within-person pain variability with anxiety and depression symptoms in 832 older adults with OA who participated in the European Project on OSteoArthritis (EPOSA): a six-country cohort study. Affective symptoms were examined with the Hospital Anxiety and Depression Scale, pain severity was assessed with the WOMAC/AUSCAN, and intra-individual pain variability was measured using pain calendars assessed at baseline, 6 and 12-18 months. Age-stratified multiple linear regression analyses adjusted for relevant confounders showed that more pain was associated with more affective symptoms in older-old participants (74.1-85 years). Moreover, older-old participants experienced fewer symptoms of anxiety (ratio=.85, 95% CI: .77-.94), depression (ratio=.90, 95% CI: .82-.98) and total affective symptoms (ratio=.87, 95% CI: .79-.94) if their pain fluctuated more. No such association was evident in younger-old participants (65-74.0 years). These findings imply that stable pain levels are more detrimental to mental health than fluctuating pain levels in older persons.

Published
2018

35. Centenarian controls increase variant effect sizes by an average twofold in an extreme case–extreme control analysis of Alzheimer’s disease

Author

Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, N.M. (author), Meijers-Heijboer, Hanne (author), Reinders, M.J.T. (author), Holstege, H. (author), Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, N.M. (author), Meijers-Heijboer, Hanne (author), Reinders, M.J.T. (author), and Holstege, H. (author)

Abstract

The detection of genetic loci associated with Alzheimer’s disease (AD) requires large numbers of cases and controls because variant effect sizes are mostly small. We hypothesized that variant effect sizes should increase when individuals who represent the extreme ends of a disease spectrum are considered, as their genomes are assumed to be maximally enriched or depleted with disease-associated genetic variants. We used 1,073 extensively phenotyped AD cases with relatively young age at onset as extreme cases (66.3 ± 7.9 years), 1,664 age-matched controls (66.0 ± 6.5 years) and 255 cognitively healthy centenarians as extreme controls (101.4 ± 1.3 years). We estimated the effect size of 29 variants that were previously associated with AD in genome-wide association studies. Comparing extreme AD cases with centenarian controls increased the variant effect size relative to published effect sizes by on average 1.90-fold (SE = 0.29, p = 9.0 × 10−4). The effect size increase was largest for the rare high-impact TREM2 (R74H) variant (6.5-fold), and significant for variants in/near ECHDC3 (4.6-fold), SLC24A4-RIN3 (4.5-fold), NME8 (3.8-fold), PLCG2 (3.3-fold), APOE-ε2 (2.2-fold), and APOE-ε4 (twofold). Comparing extreme phenotypes enabled us to replicate the AD association for 10 variants (p < 0.05) in relatively small samples. The increase in effect sizes depended mainly on using centenarians as extreme controls: the average variant effect size was not increased in a comparison of extreme AD cases and age-matched controls (0.94-fold, p = 6.8 × 10−1), suggesting that on average the tested genetic variants did not explain the extremity of the AD cases. Concluding, using centenarians as extreme controls in AD case–control studies boosts the variant effect size by on average twofold, allowing the replication of disease-association in relatively small samples., Pattern Recognition and Bioinformatics

Published
2019
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36. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

Author

Ezzati, M. and Zhou, B. and Bentham, J. and Di Cesare, M. and Bixby, H. and Danaei, G. and Hajifathalian, K. and Taddei, C. and Carrillo-Larco, R.M. and Djalalinia, S. and Khatibzadeh, S. and Lugero, C. and Peykari, N. and Zhang, W.Z. and Bennett, J. and Bilano, V. and Stevens, G.A. and Cowan, M.J. and Riley, L.M. and Chen, Z. and Hambleton, I.R. and Jackson, R.T. and Kengne, A.P. and Khang, Y.-H. and Laxmaiah, A. and Liu, J. and Malekzadeh, R. and Neuhauser, H.K. and Sorić, M. and Starc, G. and Sundström, J. and Woodward, M. and Abarca-Gómez, L. and Abdeen, Z.A. and Abu-Rmeileh, N.M. and Acosta-Cazares, B. and Adams, R.J. and Aekplakorn, W. and Afsana, K. and Aguilar-Salinas, C.A. and Agyemang, C. and Ahmad, N.A. and Ahmadvand, A. and Ahrens, W. and Ajlouni, K. and Akhtaeva, N. and Al-Raddadi, R. and Ali, M.M. and Ali, O. and Alkerwi, A. and Aly, E. and Amarapurkar, D.N. and Amouyel, P. and Amuzu, A. and Andersen, L.B. and Anderssen, S.A. and Ängquist, L.H. and Anjana, R.M. and Ansong, D. and Aounallah-Skhiri, H. and Araújo, J. and Ariansen, I. and Aris, T. and Arlappa, N. and Arveiler, D. and Aryal, K.K. and Aspelund, T. and Assah, F.K. and Assunção, M.C.F. and Avdicová, M. and Azevedo, A. and Azizi, F. and Babu, B.V. and Bahijri, S. and Balakrishna, N. and Bamoshmoosh, M. and Banach, M. and Bandosz, P. and Banegas, J.R. and Barbagallo, C.M. and Barceló, A. and Barkat, A. and Barros, A.J.D. and Barros, M.V. and Bata, I. and Batieha, A.M. and Batyrbek, A. and Baur, L.A. and Beaglehole, R. and Romdhane, H.B. and Benet, M. and Benson, L.S. and Bernabe-Ortiz, A. and Bernotiene, G. and Bettiol, H. and Bhagyalaxmi, A. and Bharadwaj, S. and Bhargava, S.K. and Bi, Y. and Bikbov, M. and Bista, B. and Bjerregaard, P. and Bjertness, E. and Bjertness, M.B. and Björkelund, C. and Blokstra, A. and Bo, S. and Bobak, M. and Boeing, H. and Boggia, J.G. and Boissonnet, C.P. and Bongard, V. and Borchini, R. and Bovet, P. and Braeckman, L. and Brajkovich, I. and Branca, F. and Breckenkamp, J. and Brenner, H. and Brewster, L.M. and Bruno, G. and Bueno-de-Mesquita, H.B. and Bugge, A. and Burns, C. and Bursztyn, M. and de León, A.C. and Cacciottolo, J. and Cai, H. and Cameron, C. and Can, G. and Cândido, A.P.C. and Capuano, V. and Cardoso, V.C. and Carlsson, A.C. and Carvalho, M.J. and Casanueva, F.F. and Casas, J.-P. and Caserta, C.A. and Chamukuttan, S. and Chan, A.W. and Chan, Q. and Chaturvedi, H.K. and Chaturvedi, N. and Chen, C.-J. and Chen, F. and Chen, H. and Chen, S. and Cheng, C.-Y. and Dekkaki, I.C. and Chetrit, A. and Chiolero, A. and Chiou, S.-T. and Chirita-Emandi, A. and Chirlaque, M.-D. and Cho, B. and Cho, Y. and Christofaro, D.G. and Chudek, J. and Cifkova, R. and Cinteza, E. and Claessens, F. and Clays, E. and Concin, H. and Cooper, C. and Cooper, R. and Coppinger, T.C. and Costanzo, S. and Cottel, D. and Cowell, C. and Craig, C.L. and Crujeiras, A.B. and Cruz, J.J. and D'Arrigo, G. and d'Orsi, E. and Dallongeville, J. and Damasceno, A. and Dankner, R. and Dantoft, T.M. and Dauchet, L. and Davletov, K. and De Backer, G. and De Bacquer, D. and de Gaetano, G. and De Henauw, S. and de Oliveira, P.D. and De Smedt, D. and Deepa, M. and Dehghan, A. and Delisle, H. and Deschamps, V. and Dhana, K. and Di Castelnuovo, A.F. and Dias-da-Costa, J.S. and Diaz, A. and Dickerson, T.T. and Do, H.T.P. and Dobson, A.J. and Donfrancesco, C. and Donoso, S.P. and Döring, A. and Dorobantu, M. and Doua, K. and Drygas, W. and Dulskiene, V. and Džakula, A. and Dzerve, V. and Dziankowska-Zaborszczyk, E. and Eggertsen, R. and Ekelund, U. and El Ati, J. and Elliott, P. and Elosua, R. and Erasmus, R.T. and Erem, C. and Eriksen, L. and Eriksson, J.G. and Escobedo-de la Peña, J. and Evans, A. and Faeh, D. and Fall, C.H. and Farzadfar, F. and Felix-Redondo, F.J. and Ferguson, T.S. and Fernandes, R.A. and Fernández-Bergés, D. and Ferrante, D. and Ferrari, M. and Ferreccio, C. and Ferrieres, J. and Finn, J.D. and Fischer, K. and Föger, B. and Foo, L.H. and Forslund, A.-S. and Forsner, M. and Fouad, H.M. and Francis, D.K. and Franco, M.C. and Franco, O.H. and Frontera, G. and Fuchs, F.D. and Fuchs, S.C. and Fujita, Y. and Furusawa, T. and Gaciong, Z. and Galvano, F. and Garcia-de-la-Hera, M. and Gareta, D. and Garnett, S.P. and Gaspoz, J.-M. and Gasull, M. and Gates, L. and Geleijnse, J.M. and Ghasemian, A. and Ghimire, A. and Giampaoli, S. and Gianfagna, F. and Gill, T.K. and Giovannelli, J. and Goldsmith, R.A. and Gonçalves, H. and Gonzalez-Gross, M. and González-Rivas, J.P. and Gorbea, M.B. and Gottrand, F. and Graff-Iversen, S. and Grafnetter, D. and Grajda, A. and Grammatikopoulou, M.G. and Gregor, R.D. and Grodzicki, T. and Grøntved, A. and Grosso, G. and Gruden, G. and Grujic, V. and Gu, D. and Guan, O.P. and Gudmundsson, E.F. and Gudnason, V. and Guerrero, R. and Guessous, I. and Guimaraes, A.L. and Gulliford, M.C. and Gunnlaugsdottir, J. and Gunter, M. and Gupta, P.C. and Gupta, R. and Gureje, O. and Gurzkowska, B. and Gutierrez, L. and Gutzwiller, F. and Hadaegh, F. and Halkjær, J. and Hardy, R. and Kumar, R.H. and Hata, J. and Hayes, A.J. and He, J. and He, Y. and Hendriks, M.E. and Henriques, A. and Cadena, L.H. and Herrala, S. and Heshmat, R. and Hihtaniemi, I.T. and Ho, S.Y. and Ho, S.C. and Hobbs, M. and Hofman, A. and Dinc, G.H. and Horimoto, A.R. and Hormiga, C.M. and Horta, B.L. and Houti, L. and Howitt, C. and Htay, T.T. and Htet, A.S. and Htike, M.M.T. and Hu, Y. and Huerta, J.M. and Huisman, M. and Husseini, A.S. and Huybrechts, I. and Hwalla, N. and Iacoviello, L. and Iannone, A.G. and Ibrahim, M.M. and Wong, N.I. and Ikeda, N. and Ikram, M.A. and Irazola, V.E. and Islam, M. and al-Safi Ismail, A. and Ivkovic, V. and Iwasaki, M. and Jacobs, J.M. and Jaddou, H. and Jafar, T. and Jamrozik, K. and Janszky, I. and Jasienska, G. and Jelaković, A. and Jelaković, B. and Jennings, G. and Jeong, S.-L. and Jiang, C.Q. and Joffres, M. and Johansson, M. and Jokelainen, J.J. and Jonas, J.B. and Jørgensen, T. and Joshi, P. and Jóźwiak, J. and Juolevi, A. and Jurak, G. and Jureša, V. and Kaaks, R. and Kafatos, A. and Kajantie, E.O. and Kalter-Leibovici, O. and Kamaruddin, N.A. and Karki, K.B. and Kasaeian, A. and Katz, J. and Kauhanen, J. and Kaur, P. and Kavousi, M. and Kazakbaeva, G. and Keil, U. and Boker, L.K. and Keinänen-Kiukaanniemi, S. and Kelishadi, R. and Kemper, H.C.G. and Kengne, A.P. and Kerimkulova, A. and Kersting, M. and Key, T. and Khader, Y.S. and Khalili, D. and Khateeb, M. and Khaw, K.-T. and Kiechl-Kohlendorfer, U. and Kiechl, S. and Killewo, J. and Kim, J. and Kim, Y.-Y. and Klumbiene, J. and Knoflach, M. and Kolle, E. and Kolsteren, P. and Korrovits, P. and Koskinen, S. and Kouda, K. and Kowlessur, S. and Koziel, S. and Kriemler, S. and Kristensen, P.L. and Krokstad, S. and Kromhout, D. and Kruger, H.S. and Kubinova, R. and Kuciene, R. and Kuh, D. and Kujala, U.M. and Kulaga, Z. and Kumar, R.K. and Kurjata, P. and Kusuma, Y.S. and Kuulasmaa, K. and 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S.T. and McLachlan, S. and McLean, R.M. and McLean, S.B. and McNulty, B.A. and Mediene-Benchekor, S. and Medzioniene, J. and Meirhaeghe, A. and Meisinger, C. and Menezes, A.B. and Menon, G.R. and Meshram, I.I. and Metspalu, A. and Meyer, H.E. and Mi, J. and Mikkel, K. and Miller, J.C. and Minderico, C.S. and Miquel, J.F. and Miranda, J.J. and Mirrakhimov, E. and Mišigoj-Durakovic, M. and Modesti, P.A. and Mohamed, M.K. and Mohammad, K. and Mohammadifard, N. and Mohan, V. and Mohanna, S. and Yusoff, M.F.M.D. and Møllehave, L.T. and Møller, N.C. and Molnár, D. and Momenan, A. and Mondo, C.K. and Monyeki, K.D.K. and Moon, J.S. and Moreira, L.B. and Morejon, A. and Moreno, L.A. and Morgan, K. and Moschonis, G. and Mossakowska, M. and Mostafa, A. and Mota, J. and Motlagh, M.E. and Motta, J. and Msyamboza, K.P. and ThetMu, T. and Muiesan, M.L. and Müller-Nurasyid, M. and Murphy, N. and Mursu, J. and Musil, V. and Nabipour, I. and Nagel, G. and Naidu, B.M. and Nakamura, H. and Námešná, J. and 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and Sonestedt, E. and Song, Y. and Sørensen, T.I.A. and Soric, M. and Jérome, C.S. and Soumare, A. and Staessen, J.A. and Stathopoulou, M.G. and Stavreski, B. and Steene-Johannessen, J. and Stehle, P. and Stein, A.D. and Stergiou, G.S. and Stessman, J. and Stieber, J. and Stöckl, D. and Stocks, T. and Stokwiszewski, J. and Stronks, K. and Strufaldi, M.W. and Sun, C.-A. and Sung, Y.-T. and Suriyawongpaisal, P. and Sy, R.G. and Tai, E.S. and Tammesoo, M.-L. and Tamosiunas, A. and Tan, E.J. and Tang, X. and Tanser, F. and Tao, Y. and Tarawneh, M.R. and Tarqui-Mamani, C.B. and Tautu, O.-F. and Taylor, A. and Theobald, H. and Theodoridis, X. and Thijs, L. and Thuesen, B.H. and Tjonneland, A. and Tolonen, H.K. and Tolstrup, J.S. and Topbas, M. and Topór-Madry, R. and Tormo, M.J. and Torrent, M. and Traissac, P. and Trichopoulos, D. and Trichopoulou, A. and Trinh, O.T.H. and Trivedi, A. and Tshepo, L. and Tulloch-Reid, M.K. and Tullu, F. and Tuomainen, T.-P. and Tuomilehto, J. and Turley, M.L. and Tynelius, P. and Tzourio, C. and Ueda, P. and Ugel, E.E. and Ulmer, H. and Uusitalo, H.M.T. and Valdivia, G. and Valvi, D. and van der Schouw, Y.T. and Van Herck, K. and Van Minh, H. and van Rossem, L. and Van Schoor, N.M. and van Valkengoed, I.G.M. and Vanderschueren, D. and Vanuzzo, D. and Vatten, L. and Vega, T. and Velasquez-Melendez, G. and Veronesi, G. and Verschuren, W.M.M. and Verstraeten, R. and Victora, C.G. and Viet, L. and Viikari-Juntura, E. and Vineis, P. and Vioque, J. and Virtanen, J.K. and Visvikis-Siest, S. and Viswanathan, B. and Vlasoff, T. and Vollenweider, P. and Voutilainen, S. and Wade, A.N. and Wagner, A. and Walton, J. and Wan Bebakar, W.M. and Wan Mohamud, W.N. and Wanderley, R.S., Jr. and Wang, M.-D. and Wang, Q. and Wang, Y.X. and Wang, Y.-W. and Wannamethee, S.G. and Wareham, N. and Wedderkopp, N. and Weerasekera, D. and Whincup, P.H. and Widhalm, K. and Widyahening, I.S. and Wiecek, A. and Wijga, A.H. and Wilks, R.J. and Willeit, J. and Willeit, 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Brazil, Shiraz University of Medical Sciences, Iran, Institute of Internal and Preventive Medicine, Russian Federation, Harokopio University, Greece, University of Otago, New Zealand, University of Padova, Italy, Lausanne University Hospital, Switzerland, CIBERCV, Spain, Emory University, United States, UiT The Arctic University of Norway, Norway, Cape Peninsula University of Technology, South Africa, Gorgas Memorial Institute of Health Studies, Panama, Brown University, United States, University of Edinburgh, United Kingdom, Statistics Canada, Canada, University College Dublin, Ireland, Institut National de la Santé et de la Recherche Médicale, France, Lusófona University, Portugal, Universita' degli Studi di Firenze, Italy, Ain Shams University, Egypt, Hypertension Research Center, Iran, University of Pécs, Hungary, Seoul National University Children's Hospital, South Korea, University Medical Science, Cuba, Universidad de Zaragoza, Spain, RCSI Dublin, Ireland, La Trobe University, Australia, International Institute of Molecular and Cell Biology, Poland, Ahvaz Jundishapur University of Medical Sciences, Iran, Gorgas Memorial Institute of Public Health, Panama, World Health Organization Country Office, Malawi, Department of Public Health, Myanmar, University of Brescia, Italy, Bushehr University of Medical Sciences, Iran, Ulm University, Germany, Kobe University, Japan, Suraj Eye Institute, India, University Medicine of Greifswald, Germany, INSERM, France, National Institute of Hygiene and Epidemiology, Viet Nam, The University of Pharmacy and Medicine of Ho Chi Minh City, Viet Nam, Hanoi Medical University, Viet Nam, National Hospital of Endocrinology, Viet Nam, Miami Veterans Affairs Healthcare System, United States, University of Turku Tyks, Finland, Heartfile, Pakistan, Eastern Mediterranean Public Health Network, Jordan, Tachikawa General Hospital, Japan, Academic Hospital of Paramaribo, Suriname, Ministry of Health, Brunei Darussalam, University of Madeira, Portugal, MRC Lifecourse Epidemiology Unit, United Kingdom, Aarhus University, Denmark, Kwame Nkrumah University of Science and Technology, Ghana, Institute for Social and Preventive Medicine, Switzerland, University of Coimbra, Portugal, Cancer Prevention and Research Institute, Italy, Ruprecht-Karls-University of Heidelberg, Germany, IRCCS Casa Sollievo della Sofferenza, Italy, Zayed University, United Arab Emirates, Catholic University of Daegu, South Korea, Jivandeep Hospital, India, University Hospital Centre Zagreb, Croatia, University Medical Center Utrecht, Netherlands, Vietnam National Heart Institute, Viet Nam, University of Sarajevo, Bosnia and Herzegovina, Cardiovascular Prevention Centre Udine, Italy, Ministry of Health and Medical Services, Solomon Islands, Public Health Agency of Catalonia, Spain, University of Split, Croatia, Digestive Oncology Research Center, Iran, Digestive Disease Research Institute, Iran, Alborz University of Medical Sciences, Iran, Ministry of Health, Viet Nam, University of Turku, Finland, Universiti Putra Malaysia, Malaysia, University of Malaya, Malaysia, University of Valencia, Spain, University of the Philippines, Philippines, Minas Gerais State Secretariat for Health, Brazil, Health Center San Agustín, Spain, PharmAccess Foundation, Netherlands, Universidade Nove de Julho, Brazil, Public Health Agency of Canada, Canada, Canarian Health Service, Spain, Universidad Industrial de Santander, Colombia, Instituto Nacional de Salud Pública, Mexico, Sitaram Bhartia Institute of Science and Research, India, Marmara University, Turkey, CIBER de Epidemiología y Salud Pública, Spain, University of Helsinki, Finland, National Institute of Health, Peru, Catalan Department of Health, Spain, Universidade de Lisboa, Portugal, University of Sao Paulo Clinics Hospital, Brazil, South Karelia Social and Health Care District, Finland, Isfahan Cardiovascular Research Center, Iran, Research and Education Institute of Child Health, Cyprus, Hospital Italiano de Buenos Aires, Argentina, Lagos State University College of Medicine, Nigeria, The University of Tokyo, Japan, Samsung Medical Center, South Korea, Federal University of Santa Catarina, Brazil, St Vincent's Hospital, Australia, Academic Medical Center Amsterdam, Netherlands, University of Bari, Italy, Lund University, Sweden, University of Copenhagen, Denmark, Institut Régional de Santé Publique, Benin, University of Bordeaux, France, University of Leuven, Belgium, Bonn University, Germany, Sotiria Hospital, Greece, National Institute of Public Health- National Institute of Hygiene, Poland, Fu Jen Catholic University, Taiwan, Ministry of Health, Jordan, Health Service of Murcia, Spain, IB-SALUT Area de Salut de Menorca, Spain, Institut de Recherche pour le Développement, France, Hellenic Health Foundation, Greece, GovernmentMedical College, India, Sefako Makgatho Health Science University, South Africa, Addis Ababa University, Ethiopia, Dasman Diabetes Institute, Kuwait, Ministry of Health, New Zealand, Universidad Centro-Occidental Lisandro Alvarado, Venezuela, University of Tampere Tays Eye Center, Finland, Utrecht University, Netherlands, Hanoi University of Public Health, Viet Nam, Amsterdam Public Health Research Institute, Netherlands, Universidade Federal de Minas Gerais, Brazil, Finnish Institute of Occupational Health, Finland, Universidad Miguel Hernandez, Spain, North Karelian Center for Public Health, Finland, University of the Witwatersrand, South Africa, University of Strasbourg, France, Institute for Medical Research, Malaysia, Xinjiang Medical University, China, Capital Medical University, China, St George's, University of London, United Kingdom, Medical University of Vienna, Austria, Universitas Indonesia, Indonesia, National Institute of Public Health-National Institute of Hygiene, Poland, Institute of Food and Nutrition Development of Ministry of Agriculture, China, Children's Hospital of Fudan University, China, University of Cyprus, Cyprus, Universiti Teknologi MARA, Malaysia, Inner Mongolia Medical University, China, Universidad Politécnica de Madrid, Spain, State University of Montes Claros, Brazil, and University of Limpopo, South Africa

Subjects
sense organs
Abstract

Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups. © The Author(s) 2018.

Published
2018

37. Within-Person Pain Variability and Mental Health in Older Adults With Osteoarthritis: An Analysis Across 6 European Cohorts

Author

de Koning, Elisa J., primary, Timmermans, Erik J., additional, van Schoor, Natasja M., additional, Stubbs, Brendon, additional, van den Kommer, Tessa N., additional, Dennison, Elaine M., additional, Limongi, Federica, additional, Castell, Maria Victoria, additional, Edwards, Mark H., additional, Queipo, Rocio, additional, Cooper, Cyrus, additional, Siviero, Paola, additional, van der Pas, Suzan, additional, Pedersen, Nancy L., additional, Sánchez-Martínez, Mercedes, additional, Deeg, Dorly J.H., additional, Denkinger, Michael D., additional, Nikolaus, T., additional, Denkinger, M., additional, Peter, R., additional, Herbolsheimer, F., additional, Maggi, S., additional, Zambon, S., additional, Limongi, F., additional, Noale, M., additional, Siviero, P., additional, Deeg, D.J.H., additional, van der Pas, S., additional, van Schoor, N.M., additional, Schaap, L.A., additional, Timmermans, E.J., additional, Lips, P., additional, Otero, Á., additional, Castell, M.V., additional, Sanchez-Martinez, M., additional, Pedersen, N.L., additional, Dennison, E.M., additional, Cooper, C., additional, and Edwards, M.H., additional

Published
2018
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38. Within-Person Pain Variability and Mental Health in Older Adults With Osteoarthritis: An Analysis Across 6 European Cohorts

Author

de Koning, Elisa J., Timmermans, E.J., van Schoor, N.M., Stubbs, Brendon, van den Kommer, Tessa N., Dennison, E.M., Limongi, Federica, Castell, Maria Victoria, Edwards, M.H., Queipo, Rocio, Cooper, Cyrus, Siviero, Paola, van der Pas, Suzan, Pedersen, N.L., Sánchez-Martínez, Mercedes, Deeg, D.J.H., Denkinger, Michael D., Nikolaus, T., Denkinger, M., Peter, R., Herbolsheimer, F., Maggi, S., Zambon, S., Limongi, F., Noale, M., Siviero, P., van der Pas, S., Schaap, L.A., Lips, P., Otero, Á., Castell, M.V., Sanchez-Martinez, M., Cooper, C., de Koning, Elisa J., Timmermans, E.J., van Schoor, N.M., Stubbs, Brendon, van den Kommer, Tessa N., Dennison, E.M., Limongi, Federica, Castell, Maria Victoria, Edwards, M.H., Queipo, Rocio, Cooper, Cyrus, Siviero, Paola, van der Pas, Suzan, Pedersen, N.L., Sánchez-Martínez, Mercedes, Deeg, D.J.H., Denkinger, Michael D., Nikolaus, T., Denkinger, M., Peter, R., Herbolsheimer, F., Maggi, S., Zambon, S., Limongi, F., Noale, M., Siviero, P., van der Pas, S., Schaap, L.A., Lips, P., Otero, Á., Castell, M.V., Sanchez-Martinez, M., and Cooper, C.

Abstract

Pain is a key symptom of Osteoarthritis (OA) and has been linked to poor mental health. Pain fluctuates over time within individuals, but a paucity of studies have considered day-to-day fluctuations of joint pain in relation to affective symptoms in older persons with OA. This study investigated the relationship of both pain severity and within-person pain variability with anxiety and depression symptoms in 832 older adults with OA who participated in the European Project on OSteoArthritis (EPOSA): a six-country cohort study. Affective symptoms were examined with the Hospital Anxiety and Depression Scale, pain severity was assessed with the WOMAC/AUSCAN, and intra-individual pain variability was measured using pain calendars assessed at baseline, 6 and 12-18 months. Age-stratified multiple linear regression analyses adjusted for relevant confounders showed that more pain was associated with more affective symptoms in older-old participants (74.1-85 years). Moreover, older-old participants experienced fewer symptoms of anxiety (ratio=.85, 95% CI: .77-.94), depression (ratio=.90, 95% CI: .82-.98) and total affective symptoms (ratio=.87, 95% CI: .79-.94) if their pain fluctuated more. No such association was evident in younger-old participants (65-74.0 years). These findings imply that stable pain levels are more detrimental to mental health than fluctuating pain levels in older persons. PERSPECTIVE: This study showed that more severe and stable joint pain levels were associated with anxiety and depressive symptoms in older persons with OA. These findings emphasize the importance of measuring pain in OA at multiple time-points, as joint pain fluctuations may be an indicator for the presence of affective symptoms.

Published
2018
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41. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Author

Zillikens, M.C., Demissie, S., Hsu, Y.H., Yerges-Armstrong, L.M., Chou, W.C., Stolk, L., Livshits, G., Broer, L., Johnson, T., Koller, D.L., Kutalik, Z., Luan, J., Malkin, I., Ried, J.S., Smith, A.V., Thorleifsson, G., Vandenput, L., Hua Zhao, J., Zhang, W., Aghdassi, A., Åkesson, K., Amin, N., Baier, L.J., Barroso, I., Bennett, D.A., Bertram, L., Biffar, R., Bochud, M., Boehnke, M., Borecki, I.B., Buchman, A.S., Byberg, L., Campbell, H., Campos Obanda, N., Cauley, J.A., Cawthon, P.M., Cederberg, H., Chen, Z., Cho, N.H., Jin Choi, H., Claussnitzer, M., Collins, F., Cummings, S.R., De Jager, P.L., Demuth, I., Dhonukshe-Rutten, RAM, Diatchenko, L., Eiriksdottir, G., Enneman, A.W., Erdos, M., Eriksson, J.G., Eriksson, J., Estrada, K., Evans, D.S., Feitosa, M.F., Fu, M., Garcia, M., Gieger, C., Girke, T., Glazer, N.L., Grallert, H., Grewal, J., Han, B.G., Hanson, R.L., Hayward, C., Hofman, A., Hoffman, E.P., Homuth, G., Hsueh, W.C., Hubal, M.J., Hubbard, A., Huffman, K.M., Husted, L.B., Illig, T., Ingelsson, E., Ittermann, T., Jansson, J.O., Jordan, J.M., Jula, A., Karlsson, M., Khaw, K.T., Kilpeläinen, T.O., Klopp, N., Kloth, JSL, Koistinen, H.A., Kraus, W.E., Kritchevsky, S., Kuulasmaa, T., Kuusisto, J., Laakso, M., Lahti, J., Lang, T., Langdahl, B.L., Launer, L.J., Lee, J.Y., Lerch, M.M., Lewis, J.R., Lind, L., Lindgren, C., Liu, Y., Liu, T., Ljunggren, Ö., Lorentzon, M., Luben, R.N., Maixner, W., McGuigan, F.E., Medina-Gomez, C., Meitinger, T., Melhus, H., Mellström, D., Melov, S., Michaëlsson, K., Mitchell, B.D., Morris, A.P., Mosekilde, L., Newman, A., Nielson, C.M., O'Connell, J.R., Oostra, B.A., Orwoll, E.S., Palotie, A., Parker, S., Peacock, M., Perola, M., Peters, A., Polasek, O., Prince, R.L., Räikkönen, K., Ralston, S.H., Ripatti, S., Robbins, J.A., Rotter, J.I., Rudan, I., Salomaa, V., Satterfield, S., Schadt, E.E., Schipf, S., Scott, L., Sehmi, J., Shen, J., Soo Shin, C., Sigurdsson, G., Smith, S., Soranzo, N., Stančáková, A., Steinhagen-Thiessen, E., Streeten, E.A., Styrkarsdottir, U., Swart, KMA, Tan, S.T., Tarnopolsky, M.A., Thompson, P., Thomson, C.A., Thorsteinsdottir, U., Tikkanen, E., Tranah, G.J., Tuomilehto, J., van Schoor, N.M., Verma, A., Vollenweider, P., Völzke, H., Wactawski-Wende, J., Walker, M., Weedon, M.N., Welch, R., Wichmann, H.E., Widen, E., Williams, FMK, Wilson, J.F., Wright, N.C., Xie, W., Yu, L., Zhou, Y., Chambers, J.C., Döring, A., van Duijn, C.M., Econs, M.J., Gudnason, V., Kooner, J.S., Psaty, B.M., Spector, T.D., Stefansson, K., Rivadeneira, F., Uitterlinden, A.G., Wareham, N.J., Ossowski, V., Waterworth, D., Loos, RJF, Karasik, D., Harris, T.B., Ohlsson, C., Kiel, D.P., Zillikens, M.C., Demissie, S., Hsu, Y.H., Yerges-Armstrong, L.M., Chou, W.C., Stolk, L., Livshits, G., Broer, L., Johnson, T., Koller, D.L., Kutalik, Z., Luan, J., Malkin, I., Ried, J.S., Smith, A.V., Thorleifsson, G., Vandenput, L., Hua Zhao, J., Zhang, W., Aghdassi, A., Åkesson, K., Amin, N., Baier, L.J., Barroso, I., Bennett, D.A., Bertram, L., Biffar, R., Bochud, M., Boehnke, M., Borecki, I.B., Buchman, A.S., Byberg, L., Campbell, H., Campos Obanda, N., Cauley, J.A., Cawthon, P.M., Cederberg, H., Chen, Z., Cho, N.H., Jin Choi, H., Claussnitzer, M., Collins, F., Cummings, S.R., De Jager, P.L., Demuth, I., Dhonukshe-Rutten, RAM, Diatchenko, L., Eiriksdottir, G., Enneman, A.W., Erdos, M., Eriksson, J.G., Eriksson, J., Estrada, K., Evans, D.S., Feitosa, M.F., Fu, M., Garcia, M., Gieger, C., Girke, T., Glazer, N.L., Grallert, H., Grewal, J., Han, B.G., Hanson, R.L., Hayward, C., Hofman, A., Hoffman, E.P., Homuth, G., Hsueh, W.C., Hubal, M.J., Hubbard, A., Huffman, K.M., Husted, L.B., Illig, T., Ingelsson, E., Ittermann, T., Jansson, J.O., Jordan, J.M., Jula, A., Karlsson, M., Khaw, K.T., Kilpeläinen, T.O., Klopp, N., Kloth, JSL, Koistinen, H.A., Kraus, W.E., Kritchevsky, S., Kuulasmaa, T., Kuusisto, J., Laakso, M., Lahti, J., Lang, T., Langdahl, B.L., Launer, L.J., Lee, J.Y., Lerch, M.M., Lewis, J.R., Lind, L., Lindgren, C., Liu, Y., Liu, T., Ljunggren, Ö., Lorentzon, M., Luben, R.N., Maixner, W., McGuigan, F.E., Medina-Gomez, C., Meitinger, T., Melhus, H., Mellström, D., Melov, S., Michaëlsson, K., Mitchell, B.D., Morris, A.P., Mosekilde, L., Newman, A., Nielson, C.M., O'Connell, J.R., Oostra, B.A., Orwoll, E.S., Palotie, A., Parker, S., Peacock, M., Perola, M., Peters, A., Polasek, O., Prince, R.L., Räikkönen, K., Ralston, S.H., Ripatti, S., Robbins, J.A., Rotter, J.I., Rudan, I., Salomaa, V., Satterfield, S., Schadt, E.E., Schipf, S., Scott, L., Sehmi, J., Shen, J., Soo Shin, C., Sigurdsson, G., Smith, S., Soranzo, N., Stančáková, A., Steinhagen-Thiessen, E., Streeten, E.A., Styrkarsdottir, U., Swart, KMA, Tan, S.T., Tarnopolsky, M.A., Thompson, P., Thomson, C.A., Thorsteinsdottir, U., Tikkanen, E., Tranah, G.J., Tuomilehto, J., van Schoor, N.M., Verma, A., Vollenweider, P., Völzke, H., Wactawski-Wende, J., Walker, M., Weedon, M.N., Welch, R., Wichmann, H.E., Widen, E., Williams, FMK, Wilson, J.F., Wright, N.C., Xie, W., Yu, L., Zhou, Y., Chambers, J.C., Döring, A., van Duijn, C.M., Econs, M.J., Gudnason, V., Kooner, J.S., Psaty, B.M., Spector, T.D., Stefansson, K., Rivadeneira, F., Uitterlinden, A.G., Wareham, N.J., Ossowski, V., Waterworth, D., Loos, RJF, Karasik, D., Harris, T.B., Ohlsson, C., and Kiel, D.P.

Abstract

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10(-8)) or suggestively genome wide (p < 2.3 × 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Published
2017

42. Food sources of vitamin D and their association with 25-hydroxyvitamin D status in Dutch older adults

Author

Vaes, A.M.M., Brouwer-Brolsma, E.M., van der Zwaluw, N.L., van Wijngaarden, J.P., Berendsen, A.A.M., Van Schoor, N.M., van der Velde, N., Uitterlinden, A., Lips, P., Dhonukshe-Rutten, R.A.M., de Groot, L.C.P.G.M., Vaes, A.M.M., Brouwer-Brolsma, E.M., van der Zwaluw, N.L., van Wijngaarden, J.P., Berendsen, A.A.M., Van Schoor, N.M., van der Velde, N., Uitterlinden, A., Lips, P., Dhonukshe-Rutten, R.A.M., and de Groot, L.C.P.G.M.

Abstract

Various populations are at increased risk of developing a low vitamin D status, in particular older adults. Whereas sun exposure is considered the main source of vitamin D, especially during summer, dietary contributions should not be underestimated. This study aims to identify food sources of vitamin D that associate most strongly with serum vitamin D concentration. Data of 595 Dutch adults, aged 65 years, were analysed. Vitamin D intake was assessed with a food frequency questionnaire and 25- hydroxyvitamin D (25(OH)D) was determined in serum. Associations of total vitamin D intake and vitamin D intake from specific food groups with serum 25(OH)D status were examined by P-for trend analyses over tertiles of vitamin D intake, prevalence ratios (PRs), and spline regression. The prevalence of vitamin D deficiency was high, with 36% of the participants having a 25(OH)D status <50 nmol/L. Participants with adequate 25(OH)D concentrations were more likely to be men and more likely to be younger than participants with vitamin D deficiency. Total median vitamin D intake was 4.3mg/day, of which 4.0mg/day was provided by foods. Butter and margarine were the leading contributors to total vitamin D intake with 1.8mg/day, followed by the intake of fish and shellfish with 0.56mg/day. Participants with higher intakes of butter and margarine were 21% more likely to have a sufficient 25(OH) D status after adjustment for covariates (T1 vs. T3: PR 1.0 vs. 1.21 (95%CI: 1.03–1.42), P-for trend 0.02). None of the other food groups showed a significant association with the probability of having a sufficient 25(OH)D status. This study shows that vitamin D intake was positively associated with total serum 25 (OH)D concentration, with butter and margarine being the most important contributors to total vitamin D intake

Published
2017
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44. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

Author

Reppe, S. Wang, Y. Thompson, W.K. McEvoy, L.K. Schork, A.J. Zuber, V. LeBlanc, M. Bettella, F. Mills, I.G. Desikan, R.S. Djurovic, S. Gautvik, K.M. Dale, A.M. Andreassen, O.A. Estrada, K. Styrkarsdottir, U. Evangelou, E. Hsu, Y.-H. Duncan, E.L. Ntzani, E.E. Oei, L. Albagha, O.M.E. Amin, N. Kemp, J.P. Koller, D.L. Li, G. Liu, C.-T. Minster, R.L. Moayyeri, A. Vandenput, L. Willner, D. Xiao, S.-M. Yerges-Armstrong, L.M. Zheng, H.-F. Alonso, N. Eriksson, J. Kammerer, C.M. Kaptoge, S.K. Leo, P.J. Thorleifsson, G. Wilson, S.G. Wilson, J.F. Aalto, V. Alen, M. Aragaki, A.K. Aspelund, T. Center, J.R. Dailiana, Z. Duggan, D.J. Garcia, M. Garcia-Giralt, N. Giroux, S. Hallmans, G. Hocking, L.J. Husted, L.B. Jameson, K.A. Khusainova, R. Kim, G.S. Kooperberg, C. Koromila, T. Kruk, M. Laaksonen, M. Lacroix, A.Z. Lee, S.H. Leung, P.C. Lewis, J.R. Masi, L. Mencej-Bedrac, S. Nguyen, T.V. Nogues, X. Patel, M.S. Prezelj, J. Rose, L.M. Scollen, S. Siggeirsdottir, K. Smith, A.V. Svensson, O. Trompet, S. Trummer, O. Van Schoor, N.M. Woo, J. Zhu, K. Balcells, S. Brandi, M.L. Buckley, B.M. Cheng, S. Christiansen, C. Cooper, C. Dedoussis, G. Ford, I. Frost, M. Goltzman, D. González-Macías, J. Kähönen, M. Karlsson, M. Khusnutdinova, E. Koh, J.-M. Kollia, P. Langdahl, B.L. Leslie, W.D. Lips, P. Ljunggren, Ö. Lorenc, R.S. Marc, J. Mellström, D. Obermayer-Pietsch, B. Olmos, J.M. Pettersson-Kymmer, U. Reid, D.M. Riancho, J.A. Ridker, P.M. Rousseau, F. Slagboom, P.E. Tang, N.L.S. Urreizti, R. Van Hul, W. Viikari, J. Zarrabeitia, M.T. Aulchenko, Y.S. Castano-Betancourt, M. Grundberg, E. Herrera, L. Ingvarsson, T. Johannsdottir, H. Kwan, T. Li, R. Luben, R. Medina-Gómez, C. Palsson, S.Th. Rotter, J.I. Sigurdsson, G. Van Meurs, J.B.J. Verlaan, D. Williams, F.M.K. Wood, A.R. Zhou, Y. Pastinen, T. Raychaudhuri, S. Cauley, J.A. Chasman, D.I. Clark, G.R. Cummings, S.R. Danoy, P. Dennison, E.M. Eastell, R. Eisman, J.A. Gudnason, V. Hofman, A. Jackson, R.D. Jones, G. Jukema, J.W. Khaw, K.-T. Lehtimäki, T. Liu, Y. Lorentzon, M. McCloskey, E. Mitchell, B.D. Nandakumar, K. Nicholson, G.C. Oostra, B.A. Peacock, M. Pols, H.A.P. Prince, R.L. Raitakari, O. Reid, I.R. Robbins, J. Sambrook, P.N. Sham, P.C. Shuldiner, A.R. Tylavsky, F.A. Van Duijn, C.M. Wareham, N.J. Cupples, L.A. Econs, M.J. Evans, D.M. Harris, T.B. Kung, A.W.C. Psaty, B.M. Reeve, J. Spector, T.D. Streeten, E.A. Zillikens, M.C. Thorsteinsdottir, U. Ohlsson, C. Karasik, D. Richards, J.B. Brown, M.A. Stefansson, K. Uitterlinden, A.G. Ralston, S.H. Ioannidis, J.P.A. Kiel, D.P. Rivadeneira, F. GEFOS Consortium

Subjects
musculoskeletal diseases
Abstract

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity. © 2015 Reppe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Published
2015

45. Low vitamin D status is associated with more depressive symptoms in Dutch older adults

Author

Brouwer-Brolsma, E.M., Dhonukshe-Rutten, R.A.M., van Wijngaarden, J.P., van der Zwaluw, N.L., Sohl, E., in 't Veld, P.H., van Dijk, S.C., Swart, K.M.A., Enneman, A.W., Ham, A.C., van Schoor, N.M., van der Velde, N., Uitterlinden, A.G., Lips, P., Feskens, E.J.M., de Groot, C.P.G.M., Brouwer-Brolsma, E.M., Dhonukshe-Rutten, R.A.M., van Wijngaarden, J.P., van der Zwaluw, N.L., Sohl, E., in 't Veld, P.H., van Dijk, S.C., Swart, K.M.A., Enneman, A.W., Ham, A.C., van Schoor, N.M., van der Velde, N., Uitterlinden, A.G., Lips, P., Feskens, E.J.M., and de Groot, C.P.G.M.

Abstract

Purpose The existence of vitamin D receptors in the brain points to a possible role of vitamin D in brain function. We examined the association of vitamin D status and vitamin D-related genetic make-up with depressive symptoms amongst 2839 Dutch older adults aged =65 years. Methods 25-Hydroxyvitamin D (25(OH)D) was measured, and five ‘vitamin D-related genes’ were selected. Depressive symptoms were measured with the 15-point Geriatric Depression Scale. Results were expressed as the relative risk of the score of depressive symptoms by quartiles of 25(OH)D concentration or number of affected alleles, using the lowest quartile or minor allele group as reference. Results A clear cross-sectional and prospective association between serum 25(OH)D and depressive symptom score was observed. Fully adjusted models indicated a 22 % (RR 0.78, 95 % CI 0.68–0.89), 21 % (RR 0.79, 95 % CI 0.68–0.90), and 18 % (RR 0.82, 95 % CI 0.71–0.95) lower score of depressive symptoms in people in the second, third, and fourth 25(OH)D quartiles, when compared to people in the first quartile (P for trend

Published
2016

46. A randomized controlled trial to examine the effect of 2-year vitamin B12 and folic acid supplementation on physical performance, strength, and falling: additional findings from the B-PROOF study

Author

Swart, K.M.A., Ham, A.C., van Wijngaarden, J.P., Enneman, A.W., van Dijk, S.C., Sohl, E., Brouwer, E.M., van der Zwaluw, N.L., Zillikens, M.C., Dhonukshe-Rutten, R.A.M., van der Velde, N., Brug, J., Uitterlinden, A.G., de Groot, C.P.G.M., Lips, P., van Schoor, N.M., Swart, K.M.A., Ham, A.C., van Wijngaarden, J.P., Enneman, A.W., van Dijk, S.C., Sohl, E., Brouwer, E.M., van der Zwaluw, N.L., Zillikens, M.C., Dhonukshe-Rutten, R.A.M., van der Velde, N., Brug, J., Uitterlinden, A.G., de Groot, C.P.G.M., Lips, P., and van Schoor, N.M.

Abstract

Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12–50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0–12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95 % CI 0.9–1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95 % CI 1.1–1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80 years. These effects should be further tested in future studies

Published
2016

47. Correction: The influence of age and sex on genetic associations with adult body size and shape : a large-scale genome-wide interaction study.

Author

Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der Most, P.J., Völker, U., Vohl, M.C., Vonk, J.M., Waldenberger, M., Walker, R.W., Wennauer, R., Widén, E., Willemsen, G., Wilsgaard, T., Wright, A.F., Zillikens, M.C., van Dijk, S.C., van Schoor, N.M., Asselbergs, F.W., de Bakker, P.I., Beckmann, J.S., Beilby, J., Bennett, D.A., Bergman, R.N., Bergmann, S., Böger, C.A., Boehm, B.O., Boerwinkle, E., Boomsma, D.I., Bornstein, S.R., Bottinger, E.P., Bouchard, C., Chambers, J.C., Chanock, S.J., Chasman, D.I., Cucca, F., Cusi, D., Dedoussis, G., Erdmann, J., Eriksson, J.G., Evans, D.A., de Faire, U., Farrall, M., Ferrucci, L., Ford, I., Franke, L., Franks, P.W., Froguel, P., Gansevoort, R.T., Gieger, C., Grönberg, H., Gudnason, V., Gyllensten, U., Hall, P., Hamsten, A., van der Harst, P., Hayward, C., Heliövaara, M., Hengstenberg, C., Hicks, A.A., Hingorani, A., Hofman, A., Hu, F., Huikuri, H.V., Hveem, K., James, A.L., Jordan, J.M., Jula, A., Kähönen, M., Kajantie, E., Kathiresan, S., Kiemeney, L.A., Kivimaki, M., Knekt, P.B., Koistinen, H.A., Kooner, J.S., Koskinen, S., Kuusisto, J., Maerz, W., Martin, N.G., Laakso, M., Lakka, T.A., Lehtimäki, T., Lettre, G., Levinson, D.F., Lind, L., Lokki, M.L., Mäntyselkä, P., Melbye, M., Metspalu, A., Mitchell, B.D., Moll, F.L., Murray, J.C., Musk, A.W., Nieminen, M.S., Njølstad, I., Ohlsson, C., Oldehinkel, A.J., Oostra, B.A., Palmer, L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., Loos, R.J., Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der Most, P.J., Völker, U., Vohl, M.C., Vonk, J.M., Waldenberger, M., Walker, R.W., Wennauer, R., Widén, E., Willemsen, G., Wilsgaard, T., Wright, A.F., Zillikens, M.C., van Dijk, S.C., van Schoor, N.M., Asselbergs, F.W., de Bakker, P.I., Beckmann, J.S., Beilby, J., Bennett, D.A., Bergman, R.N., Bergmann, S., Böger, C.A., Boehm, B.O., Boerwinkle, E., Boomsma, D.I., Bornstein, S.R., Bottinger, E.P., Bouchard, C., Chambers, J.C., Chanock, S.J., Chasman, D.I., Cucca, F., Cusi, D., Dedoussis, G., Erdmann, J., Eriksson, J.G., Evans, D.A., de Faire, U., Farrall, M., Ferrucci, L., Ford, I., Franke, L., Franks, P.W., Froguel, P., Gansevoort, R.T., Gieger, C., Grönberg, H., Gudnason, V., Gyllensten, U., Hall, P., Hamsten, A., van der Harst, P., Hayward, C., Heliövaara, M., Hengstenberg, C., Hicks, A.A., Hingorani, A., Hofman, A., Hu, F., Huikuri, H.V., Hveem, K., James, A.L., Jordan, J.M., Jula, A., Kähönen, M., Kajantie, E., Kathiresan, S., Kiemeney, L.A., Kivimaki, M., Knekt, P.B., Koistinen, H.A., Kooner, J.S., Koskinen, S., Kuusisto, J., Maerz, W., Martin, N.G., Laakso, M., Lakka, T.A., Lehtimäki, T., Lettre, G., Levinson, D.F., Lind, L., Lokki, M.L., Mäntyselkä, P., Melbye, M., Metspalu, A., Mitchell, B.D., Moll, F.L., Murray, J.C., Musk, A.W., Nieminen, M.S., Njølstad, I., Ohlsson, C., Oldehinkel, A.J., Oostra, B.A., Palmer, L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., and Loos, R.J.

Abstract

This corrects the article DOI: 10.1371/journal.pgen.1005378.

Published
2016

48. Results of 2-year vitamin B treatment on cognitive performance

Author

van der Zwaluw, N.L., Dhonukshe-Rutten, R.A.M., van Wijngaarden, J.P., Brouwer, E.M., van de Rest, O., in 't Veld, P.H., Enneman, A.W., van Dijk, S.C., Ham, A.C., Swart, K.M.A., van der Velde, N., van Schoor, N.M., van der Cammen, T.J.M., Uitterlinden, A.G., Lips, P., Kessels, R.P.C., and de Groot, C.P.G.M.

Subjects
Global Nutrition, Wereldvoeding, impairment, Nutrition and Disease, homocysteine, elderly-patients, folate, folic-acid supplementation, placebo-controlled trial, Voeding en Ziekte, randomized controlled-trial, alzheimers-disease, double-blind, VLAG, metaanalysis
Abstract

Objective: We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels. Methods: This multicenter, double-blind, randomized, placebo-controlled trial included 2,919 elderly participants (65 years and older) with Hcy levels between 12 and 50 µmol/L. Participants received daily either a tablet with 400 µg folic acid and 500 µg vitamin B12 (B-vitamin group) or a placebo tablet. Both tablets contained 15 µg vitamin D3. Data were available for global cognitive functioning assessed by Mini-Mental State Examination (n = 2,556), episodic memory (n = 2,467), attention and working memory (n = 759), information processing speed (n = 731), and executive function (n = 721). Results: Mean age was 74.1 (SD 6.5) years. Hcy concentrations decreased 5.0 (95% confidence interval -5.3 to -4.7) µmol/L in the B-vitamin group and 1.3 (-1.6 to -0.9) µmol/L in the placebo group. Cognitive domain scores did not differ over time between the 2 groups, as determined by analysis of covariance. Mini-Mental State Examination score decreased with 0.1 (-0.2 to 0.0) in the B-vitamin group and 0.3 (-0.4 to -0.2) in the placebo group (p = 0.05), as determined by an independent t test. Conclusions: Two-year folic acid and vitamin B12 supplementation did not beneficially affect performance on 4 cognitive domains in elderly people with elevated Hcy levels. It may slightly slow the rate of decline of global cognition, but the reported small difference may be attributable to chance. Classification of evidence: This study provides Class I evidence that 2-year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic elderly people does not affect cognitive performance.

Published
2014

49. Diet, sun, and lifestyle as determinants of vitamin D status

Author

Lips, P.T.A.M., van Schoor, N.M., de Jongh, R.T., EMGO+ - Musculoskeletal Health, Research Institute MOVE, Internal medicine, Epidemiology and Data Science, EMGO - Musculoskeletal health, and MOVE Research Institute

Subjects
fungi, food and beverages, SDG 6 - Clean Water and Sanitation
Abstract

Vitamin D status can be assessed by measuring concentrations of 25-hydroxyvitamin D (25(OH)D). Sunlight is the most important source of vitamin D and stimulates the production of vitamin D

Published
2014
Full Text
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50. Vitamin D-Related Disorders

Author

Lips, P.T.A.M., Bravenboer, N., van Schoor, N.M., Rosen, C., EMGO+ - Musculoskeletal Health, and Research Institute MOVE

Published
2013

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