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101. Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms

Author

Slieker, R.C., Iterson, M. van, Luijk, R., Beekman, M., Zhernakova, D.V., Moed, M.H., Mei, H.L., Galen, M. van, Deelen, P., Bonder, M.J., Zhernakova, A., Uitterlinden, A.G., Tigchelaar, E.F., Stehouwer, C.D.A., Schalkwijk, C.G., Kallen, C.J.H. van der, Hofman, A., Heemst, D. van, Geus, E.J. de, Dongen, J. van, Deelen, J., Berg, L.H. van den, Meurs, J. van, Jansen, R., Hoen, P.A.C. 't, Franke, L., Wijmenga, C., Veldink, J.H., Swertz, M.A., Greevenbroek, M.M.J. van, Duijn, C.M. van, Boomsma, D.I., Slagboom, P.E., Heijmans, B.T., BIOS Consortium, Epidemiology and Data Science, Laboratory Medicine, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Internal Medicine, Epidemiology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Stem Cell Aging Leukemia and Lymphoma (SALL), MUMC+: HVC Pieken Maastricht Studie (9), RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), and Biological Psychology

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), DNA damage, DNA repair, HYPOMETHYLATION, Biology, DNA-METHYLATION CHANGES, 03 medical and health sciences, Epigenetics of physical exercise, SDG 3 - Good Health and Well-being, Journal Article, SDG 14 - Life Below Water, Variability, Gene, GENE-EXPRESSION, Genetics, DAMAGE, DNA methylation, Research, WIDE, Methylation, REGIONS, CANCER, 3. Good health, 450k, GENOME, Ageing, 030104 developmental biology, CpG site, UPDATE, STEM-CELLS
Abstract

Background Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages. Results Here, we report on the large-scale identification of 6366 age-related variably methylated positions (aVMPs) identified in 3295 whole blood DNA methylation profiles, 2044 of which have a matching RNA-seq gene expression profile. aVMPs are enriched at polycomb repressed regions and, accordingly, methylation at those positions is associated with the expression of genes encoding components of polycomb repressive complex 2 (PRC2) in trans. Further analysis revealed trans-associations for 1816 aVMPs with an additional 854 genes. These trans-associated aVMPs are characterized by either an age-related gain of methylation at CpG islands marked by PRC2 or a loss of methylation at enhancers. This distinct pattern extends to other tissues and multiple cancer types. Finally, genes associated with aVMPs in trans whose expression is variably upregulated with age (733 genes) play a key role in DNA repair and apoptosis, whereas downregulated aVMP-associated genes (121 genes) are mapped to defined pathways in cellular metabolism. Conclusions Our results link age-related changes in DNA methylation to fundamental mechanisms that are thought to drive human ageing. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1053-6) contains supplementary material, which is available to authorized users.

Published
2016

104. A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

Author

McCarthy, M.I., Porcu, E., Medici, M., Pistis, G., Volpato, C.B., Wilson, S.G., Cappola, A.R., Bos, S.D., Deelen, J., den Heijer, M., Freathy, R.M., Lahti, J., Liu, C., Lopez, L.M., Nolte, I.M., O'Connell, J.R., Tanaka, T., Trompet, S., Arnold, A., Bandinelli, S., Beekman, M., Böhringer, S., Brown, S.J., Buckley, B.M., Camaschella, C., de Craen, A.J.M., Davies, G., de Visser, M.C.H., Ford, I., Forsen, T., Frayling, T.M., Fugazzola, L., Gögele, M., Hattersley, A.T., Hermus, A.R., Hofman, A., Houwing-Duistermaat, J.J., Jensen, R.A., Kajantie, E., Kloppenburg, M., Lim, E.M., Masciullo, C., Mariotti, S., Minelli, C., Mitchell, B.D., Nagaraja, R., Netea-Maier, R.T., Palotie, A., Persani, L., Piras, M.G., Psaty, B.M., Räikkönen, K., Richards, J.B., Rivadeneira, F., Sala, C., Sabra, M.M., Sattar, N., Shields, B.M., Soranzo, N., Starr, J.M., Stott, D.J., Sweep, F.C.G.J., Usala, G., van der Klauw, M.M., van Heemst, D., van Mullem, A., H.Vermeulen, S., Visser, W.E., Walsh, J.P., Westendorp, R.G.J., Widen, E., Zhai, G., Cucca, F., Deary, I.J., Eriksson, J.G., Ferrucci, L., Fox, C.S., Jukema, J.W., Kiemeney, L.A., Pramstaller, P.P., Schlessinger, D., Shuldiner, A.R., Slagboom, E.P., Uitterlinden, A.G., Vaidya, B., Visser, T.J., Wolffenbuttel, B.H.R., Meulenbelt, I., Rotter, J.I., Spector, T.D., Hicks, A.A., Toniolo, D., Sanna, S., Peeters, R.P., Naitza, S., Internal Medicine, Clinical Genetics, Public Health, Epidemiology, Internal medicine, ICaR - Circulation and metabolism, Behavioural Sciences, Clinicum, Department of General Practice and Primary Health Care, Children's Hospital, Lastentautien yksikkö, Institute for Molecular Medicine Finland, Haartman Institute (-2014), Department of Medical and Clinical Genetics, Diabetes and Obesity Research Program, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Porcu, E, Medici, M, Pistis, G, Volpato, Cb, Wilson, Sg, Cappola, Ar, Bos, Sd, Deelen, J, DEN HEIJER, M, Freathy, Rm, Lahti, J, Liu, C, Lopez, Lm, Nolte, Im, O'Connell, Jr, Tanaka, T, Trompet, S, Arnold, A, Bandinelli, S, Beekman, M, Böhringer, S, Brown, Sj, Buckley, Bm, Camaschella, Clara, DE CRAEN, Aj, Davies, G, DE VISSER, Mc, Ford, I, Forsen, T, Frayling, Tm, Fugazzola, L, Gögele, M, Hattersley, At, Hermus, Ar, Hofman, A, HOUWING DUISTERMAAT, Jj, Jensen, Ra, Kajantie, E, Kloppenburg, M, Lim, Em, Masciullo, C, Mariotti, S, Minelli, C, Mitchell, Bd, Nagaraja, R, NETEA MAIER, Rt, Palotie, A, Persani, L, Piras, Mg, Psaty, Bm, Räikkönen, K, Richards, Jb, Rivadeneira, F, Sala, C, Sabra, Mm, Sattar, N, Shields, Bm, Soranzo, N, Starr, Jm, Stott, Dj, Sweep, Fc, Usala, G, VAN DER KLAUW, Mm, VAN HEEMST, D, VAN MULLEM, A, Vermeulen, Sh, Visser, We, Walsh, Jp, Westendorp, Rg, Widen, E, Zhai, G, Cucca, F, Deary, Ij, Eriksson, Jg, Ferrucci, L, Fox, C, Jukema, Jw, Kiemeney, La, Pramstaller, Pp, Schlessinger, D, Shuldiner, Ar, Slagboom, Ep, Uitterlinden, Ag, Vaidya, B, Visser, Tj, Wolffenbuttel, Bh, Meulenbelt, I, Rotter, Ji, Spector, Td, Hicks, Aa, Toniolo, D, Sanna, S, Peeters, Rp, and Naitza, S.

Subjects
Male, Cancer Research, endocrine system diseases, Factor binding protein 5, Thyroid Gland, FACTOR BINDING PROTEIN-5, Thyrotropin, Genome-wide association study, Expression, Aetiology, screening and detection [ONCOL 5], Growth, Hyperthyroidism, CLEFT-PALATE, Serum TSH, 0302 clinical medicine, Euthyroid, Genetics (clinical), 0303 health sciences, Sex Characteristics, factor binding protein-S, Thyroid, 3. Good health, medicine.anatomical_structure, Phenotype, NFIA, Cleft palate, GROWTH, Genome wide Association, Female, Thyroid function, hormones, hormone substitutes, and hormone antagonists, Research Article, Signal Transduction, EXPRESSION, medicine.medical_specialty, endocrine system, lcsh:QH426-470, cleft-palate, 515 Psychology, education, 030209 endocrinology & metabolism, Biology, Polymorphism, Single Nucleotide, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Thyroid-stimulating hormone, Hypothyroidism, SERUM TSH, Internal medicine, medicine, Genetics, Humans, Hormonal regulation Translational research [IGMD 6], GENOME-WIDE ASSOCIATION, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Health aging / healthy living Cardiovascular diseases [IGMD 5], 030304 developmental biology, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], Polymorphism, Genetic, THYROTROPIN, HORMONE PATHWAY GENES, Hormonal regulation [IGMD 6], R1, Thyroxine, Common variation, lcsh:Genetics, Endocrinology, HYPOTHYROIDISM, Hormone pathway genes, genome-wide association, Hormonal regulation Aetiology, screening and detection [IGMD 6], 3111 Biomedicine, COMMON VARIATION, Hormone, FOXE1, Genome-Wide Association Study, Developmental Biology
Abstract

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism., Author Summary Levels of thyroid hormones are tightly regulated by TSH produced in the pituitary, and even mild alterations in their concentrations are strong indicators of thyroid pathologies, which are very common worldwide. To identify common genetic variants associated with the highly heritable markers of thyroid function, TSH and FT4, we conducted a meta-analysis of genome-wide association studies in 26,420 and 17,520 individuals, respectively, of European ancestry with normal thyroid function. Our analysis identified 26 independent genetic variants regulating these traits, several of which are new, and confirmed previously detected polymorphisms affecting TSH (within the PDE8B gene and near CAPZB, MAF/LOC440389, and NR3C2) and FT4 (within DIO1) levels. Gender-specific differences in the genetic effects of several variants for TSH and FT4 levels were identified at several loci, which offer clues to understand the known sexual dimorphism in thyroid function and pathology. Of particular clinical interest, we show that TSH-associated loci contribute not only to normal variation, but also to TSH values outside reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings add to the developing landscape of the regulation of thyroid homeostasis and the consequences of genetic variation for thyroid related diseases.

Published
2013

105. Exome and whole genome sequencing in aging and longevity

Author

van den Akker, E., Deelen, J., Slagboom, P., and Beekman, M.

Abstract

Calendar age is the major risk factor for common disease. It is therefore expected that understanding the aging process will eventually lead to promotion of better health conditions in elderly populations. Such insight may be obtained by identifying the genetic determinants of familial and exceptional longevity and age-related disease. Research of these determinants has been performed in candidate gene, genome-wide association and linkage studies. Because exploration of the common variation in the genome did not explain much of the variation in the rate of aging and longevity, researchers in the field have only recently started to investigate the contribution of rare genetic variants to these traits. The increased throughput and decreased costs of next generation sequencing (NGS) have resulted in a great deal of novel applications for sequencing sets of candidate genes, whole exomes, and whole genomes of individuals. Most of the successful NGS applications are as yet those focused on genetic syndromes and cancers for which causal mutations are readily being identified. In this chapter, we discuss the genetic and phenomic aspects of human aging research and the use of NGS data to identify genes relevant for age-related diseases and lifespan regulation, and to investigate the accumulation of somatic genetic variation during the course of life.

Published
2015

106. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

Van Leeuwen, EM, Karssen, LC, Deelen, J, Isaacs, A, Medina-Gomez, C, Mbarek, H, Kanterakis, A, Trompet, S, Postmus, I, Verweij, N, Van Enckevort, DJ, Huffman, JE, White, CC, Feitosa, MF, Bartz, TM, Manichaikul, A, Joshi, PK, Peloso, GM, Deelen, P, Van Dijk, F, Willemsen, G, De Geus, EJ, Milaneschi, Y, Penninx, BWJH, Francioli, LC, Menelaou, A, Pulit, SL, Rivadeneira, F, Hofman, A, Oostra, BA, Franco, OH, Leach, IM, Beekman, M, De Craen, AJM, Uh, HW, Trochet, H, Hocking, LJ, Porteous, DJ, Sattar, N, Packard, CJ, Buckley, BM, Brody, JA, Bis, JC, Rotter, JI, Mychaleckyj, JC, Campbell, H, Duan, Q, Lange, LA, Wilson, JF, Hayward, C, Polasek, O, Vitart, V, Rudan, I, Wright, AF, Rich, SS, Psaty, BM, Borecki, IB, Kearney, PM, Stott, DJ, Cupples, LA, Jukema, JW, Van Der Harst, P, Sijbrands, EJ, Hottenga, JJ, Uitterlinden, AG, Swertz, MA, Van Ommen, GJB, De Bakker, PIW, Eline Slagboom, P, Boomsma, DI, Wijmenga, C, Van Duijn, CM, Neerincx, PBT, Elbers, CC, Palamara, PF, Peer, I, Abdellaoui, A, Kloosterman, WP, Van Oven, M, Vermaat, M, Li, M, Laros, JFJ, Stoneking, M, De Knijff, P, Kayser, M, Veldink, JH, Van Den Berg, LH, Byelas, H, Den Dunnen, JT, Dijkstra, M, Amin, N, Van Der Velde, KJ, and Van Setten, J

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value

Published
2015

107. In vivo efficacy of HD0471953: A novel GPR119 agonist for the treatment of type 2 diabetes mellitus

Author

'T Hart, L. M., Fritsche, A., Nijpels, G., Van Leeuwen, N., Donnelly, L. A., Dekker, J. M., Alssema, M., Fadista, J., Carlotti, F., Gjesing, A. P., Palmer, C. N., Van Haeften, T. W., Herzberg-Schäfer, S. A., Simonis-Bik, A. M., Houwing-Duistermaat, J. J., Helmer, Q., Deelen, J., Guigas, B., Hansen, T., MacHicao, F., Willemsen, G., Heine, R. J., Kramer, M. H., Holst, J. J., De Koning, E. J., Häring, H. U., Pedersen, O., Groop, L., De Geus, E. J., Slagboom, P. E., Boomsma, D. I., Eekhoff, E. M., Pearson, E. R., Diamant, M., Epidemiology and Data Science, General practice, EMGO - Lifestyle, overweight and diabetes, Dermatology, CCA - Immuno-pathogenesis, Internal medicine, ICaR - Circulation and metabolism, ICaR - Ischemia and repair, and MOVE Research Institute

Published
2015

108. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, D, Winkler, TW, Croteau-Chonka, DC, Ferreira, T, Locke, AE, Mägi, R, Strawbridge, RJ, Pers, TH, Fischer, K, Justice, AE, Workalemahu, T, Wu, JMW, Buchkovich, ML, Heard-Costa, NL, Roman, TS, Drong, AW, Song, C, Gustafsson, S, Day, FR, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, JC, Scherag, A, Vedantam, S, Wood, AR, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, CT, Schmidt, EM, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg-Gresham, JL, Buyske, S, Demirkan, A, Ehret, GB, Feitosa, MF, Goel, A, Jackson, AU, Johnson, T, Kleber, ME, Kristiansson, K, Mangino, M, Leach, IM, Medina-Gomez, C, Palmer, CD, Pasko, D, Pechlivanis, S, Peters, MJ, Prokopenko, I, Stančáková, A, Sung, YJ, Tanaka, T, Teumer, A, Van Vliet-Ostaptchouk, JV, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, GM, Bandinelli, S, Barrett, A, Bellis, C, Bennett, AJ, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, DB, Caspersen, IH, Clarke, R, Daw, EW, Deelen, J, Deelman, E, Delgado, G, Doney, AS, Eklund, N, Erdos, MR, Estrada, K, Eury, E, Friedrich, N, Garcia, ME, Giedraitis, V, Gigante, B, Go, AS, Golay, A, Grallert, H, Grammer, TB, Gräßler, J, Grewal, J, Groves, CJ, Haller, T, and Hallmans, G

Subjects
Male, ReproGen Consortium, Transcription, Genetic, Cardiovascular, Epigenesis, Genetic, Body Mass Index, PAGE Consortium, Models, Adipocytes, 2.1 Biological and endogenous factors, Insulin, Body Fat Distribution, Aetiology, Sex Characteristics, Genome, Adipogenesis, Continental Population Groups, Diabetes, Age Factors, CARDIOGRAMplusC4D Consortium, Single Nucleotide, Stroke, Europe, Adipose Tissue, GEFOS Consortium, Female, ADIPOGen Consortium, Transcription, Human, General Science & Technology, ICBP, Quantitative Trait Loci, Neovascularization, Physiologic, Polymorphism, Single Nucleotide, Models, Biological, GENIE Consortium, MAGIC Investigators, Genetic, Genetics, Humans, Obesity, Polymorphism, Physiologic, Metabolic and endocrine, Neovascularization, Nutrition, Genome, Human, Waist-Hip Ratio, CKDGen Consortium, Racial Groups, Human Genome, Biological, MuTHER Consortium, GLGC, International Endogene Consortium, Insulin Resistance, LifeLines Cohort Study, Epigenesis, Genome-Wide Association Study
Abstract

© 2015, Macmillan Publishers Limited. All rights reserved. Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P

Published
2015

109. Efficiency loss prevention in monolithically integrated thin film solar cells by improved front contact

Author

Deelen, J. van, Barink, M., Klerk, L., Voorthuijzen, P., and Hovestad, A.

Subjects
TS - Technical Sciences, Transparent conductive oxides, Industrial Innovation, TCO, TFT - Thin Film Technology, Materials Energy, Modeling, Nano Technology, Grid, Thin film solar cells
Abstract

Modeling indicates a potential efficiency boost of 17% if thin-film solar panels are featured with a metallic grid. Variations of transparent conductive oxide sheet resistance, cell length, and grid dimensions are discussed. These parameters were optimized simultaneously to obtain the best result. Moreover, the power output as a function of these parameters is mapped out to create an insight on the interrelated sensitivities to all the parameters. For thin film solar cells, there is a large gap between the record efficiencies and panel power output. It was found that for a "typical industrial" CIGS cell efficiency of 15.5%, the efficiency drops to 11.7% when it is operating under the circumstances of a monolithically integrated solar panel. Part of this gap is due to limited conductivity and transmittance of the front contact. By application of a metallic grid, the conductivity can be improved by over two order of magnitude at a transmittance loss of only a few percent as was shown experimentally. In addition, modeling was used to quantify the impact of such approach on the power output of monolithically integrated solar panels. This model includes optical and resistive losses, as well as related losses caused by the inhomogeneity of the operating voltage over the surface. Both power output and the different types of losses are mapped out for various cell configurations. Optimization of transparent conductive oxide resistance, cell length, finger width, and finger spacing of grids was performed and led to an efficiency improvement from 11.7% to 13.8% when the front contact is upgraded with a metallic grid consisting of 20 μm wide parallel fingers positioned perpendicular to the interconnect. Further optimization for a wide variety of cell and grid configurations show that for a technically more feasible size of 100 μm wide fingers, the calculated efficiency is still 13.5%. Finally, the power output is mapped out for a large number of configurations as to create an overview and insight in the interdependencies of cell configuration and finger dimensions. Copyright 2014 John Wiley & Sons, Ltd.

Published
2015

110. Routes to increasing efficiency and reducing the cost of thin-film solar panels

Author

Deelen, J. van, Barink, M., Klerk, L., Voorthuijzen, P., and Hovestad, A.

Subjects
Cost reduction, TS - Technical Sciences, Industrial Innovation, Thin film solar panels, TFT - Thin Film Technology, Materials Energy, Nano Technology, Efficiency increase
Abstract

Most development work in the laboratory is dedicated to efficiency enhancements at the cell level; improvements in efficiency can lead to higher cost-competitiveness of PV. However, the cost of panel manufacturing is an important aspect as well. For CIGS panels the deposition of the active layer is an important part of the cost, and decreasing the layer thickness can reduce costs. Moreover, cost of ownership calculations can determine how much benefit can be expected from thinner absorber layers from a cost perspective; clearly, a thinner absorber will result in reduced absorption. To avoid losses, modelling can be used to predict the efficiency and viable light management strategies. Other efficiency-enhancing technology is related to the fact that most thin-film solar panels are monolithically interconnected. The area loss involved in this type of interconnection, and the trade-off between conductivity and transmittance of the front contact, impose limits on the maximum efficiency. The impact of improving both of these aspects is demonstrated in this paper. A viable way to improve the front contact is by supplementing the front contact with a metallic pattern. The benefit and the impact of different configurations and dimensions of the cell and metallic pattern are presented.

Published
2015

111. Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI

Author

Verhaaren, BFJ, Debette, S, Bis, JC, Smith, JA, Ikram, MK, Adams, HH, Beecham, AH, Rajan, KB, Lopez, LM, Barral, S, Van Buchem, MA, Van Der Grond, J, Smith, AV, Hegenscheid, K, Aggarwal, NT, De Andrade, M, Atkinson, EJ, Beekman, M, Beiser, AS, Blanton, SH, Boerwinkle, E, Brickman, AM, Bryan, RN, Chauhan, G, Chen, CPLH, Chouraki, V, De Craen, AJM, Crivello, F, Deary, IJ, Deelen, J, De Jager, PL, Dufouil, C, Elkind, MSV, Evans, DA, Freudenberger, P, Gottesman, RF, Gunason, V, Habes, M, Heckbert, SR, Heiss, G, Hilal, S, Hofer, E, Hofman, A, Ibrahim-Verbaas, CA, Knopman, DS, Lewis, CE, Liao, J, Liewald, DCM, Luciano, M, Van Der Lugt, A, Martinez, OO, Mayeux, R, Mazoyer, B, Nalls, M, Nauck, M, Niessen, WJ, Oostra, BA, Psaty, BM, Rice, KM, Rotter, JI, Von Sarnowski, B, Schmidt, H, Schreiner, PJ, Schuur, M, Sidney, SS, Sigurdsson, S, Slagboom, PE, Stott, DJM, Van Swieten, JC, Teumer, A, Töglhofer, AM, Traylor, M, Trompet, S, Turner, ST, Tzourio, C, Uh, HW, Uitterlinden, AG, Vernooij, MW, Wang, JJ, Wong, TY, Wardlaw, JM, Windham, BG, Wittfeld, K, Wolf, C, Wright, CB, Yang, Q, Zhao, W, Zijdenbos, A, Jukema, JW, Sacco, RL, Kardia, SLR, Amouyel, P, Mosley, TH, Longstreth, WT, DeCarli, CC, Van Duijn, CM, Schmidt, R, Launer, LJ, and Grabe, HJ

Subjects
genome-wide association study, hypertension, leukoencephalopathies, polymorphisms, single nucleotide, cerebrovascular disorders, cerebral small vessel diseases
Abstract

© 2015 American Heart Association, Inc. Background-The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. Methods and Results-We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10-19) and identified novel loci on chr10q24 (P=1.6×10-9) and chr2p21 (P=4.4×10-8). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10-8) and chr2p16 (P=1.5×10-8). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). Conclusions-We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.

Published
2015

114. Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, K.F. (Koen F.), Iterson, M. (Maarten) van, Slieker, R. (Roderick), Moed, H. (Heleen), Bonder, M.J. (Marc), Van Galen, M. (Michiel), Mei, S. (Shan), Zhernakova, A. (Alexandra), Berg, L.H. (Leonard) van den, Deelen, J. (Joris), Dongen, J. (Jenny) van, Heemst, D. (Diana) van, Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Kallen, C.J. van der, Schalkwijk, C.G. (Casper), Stehouwer, C.D. (Coen), Tigchelaar, E.F. (Ettje F.), Uitterlinden, A.G. (André), Willemsen, G.A.H.M. (Gonneke), Franke, L. (Lude), 't Hoen, P.A.C. (Peter A.C.), Jansen, R., Meurs, J.B.J. (Joyce) van, Boomsma, D.I. (Dorret), Duijn, C.M. (Cornelia) van, Greevenbroek, M.M. van, Veldink, J.H. (Jan), Wijmenga, C. (Cisca), Zwet, E.W. (Erik) van, Slagboom, P.E. (Eline), Jukema, J.W. (Jan Wouter), Heijmans, B.T. (Bastiaan), Dekkers, K.F. (Koen F.), Iterson, M. (Maarten) van, Slieker, R. (Roderick), Moed, H. (Heleen), Bonder, M.J. (Marc), Van Galen, M. (Michiel), Mei, S. (Shan), Zhernakova, A. (Alexandra), Berg, L.H. (Leonard) van den, Deelen, J. (Joris), Dongen, J. (Jenny) van, Heemst, D. (Diana) van, Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Kallen, C.J. van der, Schalkwijk, C.G. (Casper), Stehouwer, C.D. (Coen), Tigchelaar, E.F. (Ettje F.), Uitterlinden, A.G. (André), Willemsen, G.A.H.M. (Gonneke), Franke, L. (Lude), 't Hoen, P.A.C. (Peter A.C.), Jansen, R., Meurs, J.B.J. (Joyce) van, Boomsma, D.I. (Dorret), Duijn, C.M. (Cornelia) van, Greevenbroek, M.M. van, Veldink, J.H. (Jan), Wijmenga, C. (Cisca), Zwet, E.W. (Erik) van, Slagboom, P.E. (Eline), Jukema, J.W. (Jan Wouter), and Heijmans, B.T. (Bastiaan)

Abstract

Background: Cells can be primed by external stimuli to obtain a long-term epigenetic memory. We hypothesize that long-term exposure to elevated blood lipids can prime circulating immune cells through changes in DNA methylation, a process that may contribute to the development of atherosclerosis. To interrogate the causal relationship between triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels and genome-wide DNA methylation while excluding confounding and pleiotropy, we perform a stepwise Mendelian randomization analysis in whole blood of 3296 individuals. Results: This analysis shows that differential methylation is the consequence of inter-individual variation in blood lipid levels and not vice versa. Specifically, we observe an effect of triglycerides on DNA methylation at three CpGs, of LDL cholesterol at one CpG, and of HDL cholesterol at two CpGs using multivariable Mendelian randomization. Using RNA-seq data available for a large subset of individuals (N = 2044), DNA methylation of these six CpGs is associated with the expression of CPT1A and SREBF1 (for triglycerides), DHCR24 (for LDL cholesterol) and A

Published
2016
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115. Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms

Author

Slieker, R. (Roderick), Iterson, M. (Maarten) van, Luijk, R. (René), Beekman, M. (Marian), Zhernakova, A. (Alexandra), Moed, H. (Heleen), Mei, S. (Shan), Van Galen, M. (Michiel), Deelen, P. (Patrick), Bonder, M.J. (Marc), Uitterlinden, A.G. (André), Tigchelaar, E.F. (Ettje F.), Stehouwer, C.D.A. (Coen D.A.), Schalkwijk, C.G. (Casper), Kallen, C.J. van der, Hofman, A. (Albert), Heemst, D. (Diana) van, Geus, E.J.C. (Eco) de, Dongen, J. (Jenny) van, Deelen, J. (Joris), Berg, L.H. (Leonard) van den, Meurs, J.B.J. (Joyce) van, Jansen, R., Hoen, P.A.C. (Peter) 't, Franke, L. (Lude), Wijmenga, C. (Cisca), Veldink, J.H. (Jan), Swertz, M. (Morris), Greevenbroek, M.M. van, Duijn, C.M. (Cornelia) van, Boomsma, D.I. (Dorret), Slagboom, P.E. (Eline), Heijmans, B.T. (Bastiaan), Slieker, R. (Roderick), Iterson, M. (Maarten) van, Luijk, R. (René), Beekman, M. (Marian), Zhernakova, A. (Alexandra), Moed, H. (Heleen), Mei, S. (Shan), Van Galen, M. (Michiel), Deelen, P. (Patrick), Bonder, M.J. (Marc), Uitterlinden, A.G. (André), Tigchelaar, E.F. (Ettje F.), Stehouwer, C.D.A. (Coen D.A.), Schalkwijk, C.G. (Casper), Kallen, C.J. van der, Hofman, A. (Albert), Heemst, D. (Diana) van, Geus, E.J.C. (Eco) de, Dongen, J. (Jenny) van, Deelen, J. (Joris), Berg, L.H. (Leonard) van den, Meurs, J.B.J. (Joyce) van, Jansen, R., Hoen, P.A.C. (Peter) 't, Franke, L. (Lude), Wijmenga, C. (Cisca), Veldink, J.H. (Jan), Swertz, M. (Morris), Greevenbroek, M.M. van, Duijn, C.M. (Cornelia) van, Boomsma, D.I. (Dorret), Slagboom, P.E. (Eline), and Heijmans, B.T. (Bastiaan)

Abstract

Background: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages. Results: Here, we report on the large-scale identification of 6366 age-related variably methylated positions (aVMPs) identified in 3295 whole blood DNA methylation profiles, 2044 of which have a matching RNA-seq gene expression profile. aVMPs are enriched at polycomb repressed regions and, accordingly, methylation at those positions is associated with the expression of genes encoding components of polycomb repressive complex 2 (PRC2) in trans. Further analysis revealed trans-associations for 1816 aVMPs with an additional 854 genes. These trans-associated aVMPs are characterized by either an age-related g

Published
2016
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116. To the editor: Uncompromised 10-year survival of oldest old carrying somatic mutations in DNMT3A and TET2

Author

Akker, E.B. (Erik) van den, Pitts, S.J. (Steven J.), Deelen, J. (Joris), Moed, H. (Heleen), Potluri, S. (Shobha), Rooij, J.G.J. (Jeroen) van, Suchiman, H.E.D. (Eka), Lakenberg, N. (Nico), De Dijcker, W.J. (Wesley J.), Uitterlinden, A.G. (André), Kraaij, R. (Robert), Hofman, A. (Albert), De Craen, A.J.M. (Anton J. M.), Houwing-Duistermaat, J.J. (Jeanine), Van Ommen, G.-J.B. (Gert-Jan B.), Cox, D.R. (David), Meurs, J.B.J. (Joyce) van, Beekman, M. (Marian), Reinders, M.J. (Marcel), Slagboom, P.E. (Eline), Akker, E.B. (Erik) van den, Pitts, S.J. (Steven J.), Deelen, J. (Joris), Moed, H. (Heleen), Potluri, S. (Shobha), Rooij, J.G.J. (Jeroen) van, Suchiman, H.E.D. (Eka), Lakenberg, N. (Nico), De Dijcker, W.J. (Wesley J.), Uitterlinden, A.G. (André), Kraaij, R. (Robert), Hofman, A. (Albert), De Craen, A.J.M. (Anton J. M.), Houwing-Duistermaat, J.J. (Jeanine), Van Ommen, G.-J.B. (Gert-Jan B.), Cox, D.R. (David), Meurs, J.B.J. (Joyce) van, Beekman, M. (Marian), Reinders, M.J. (Marcel), and Slagboom, P.E. (Eline)

Published
2016
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117. Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

Author

Leeuwen, E.M. (Elisa) van, Sabo, A. (Aniko), Bis, J.C. (Joshua), Huffman, J.E. (Jennifer), Manichaikul, A. (Ani), Smith, A.V. (Davey), Feitosa, M.F. (Mary Furlan), Demissie, S. (Serkalem), Joshi, P.K. (Peter), Duan, Q. (Qing), Marten, J. (Jonathan), Klinken, J.B. (Jan Bert) van, Surakka, I. (Ida), Nolte, I.M. (Ilja), Zhang, W. (Weihua), Mbarek, H., Li-Gao, R. (Ruifang), Trompet, S. (Stella), Verweij, N. (Niek), Evangelou, E. (Evangelos), Lyytikäinen, L.-P. (Leo-Pekka), Tayo, B. (Bamidele), Deelen, J. (Joris), Most, P.J. (Peter) van der, Van Der Laan, S.W. (Sander W.), Arking, D.E. (Dan E.), Morrison, A. (Alanna), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Sijbrands, E.J.G. (Eric), Uitterlinden, A.G. (André), Mychaleckyj, J.C. (Josyf), Campbell, A. (Archie), Hocking, L.J. (Lynne), Padmanabhan, S. (Sandosh), Brody, J.A. (Jennifer A.), Rice, K.M. (Kenneth), White, C.C. (Charles), Harris, T.B. (Tamara), Isaacs, A.J. (Aaron), Campbell, H. (Harry), Lange, L.A. (Leslie), Rudan, I. (Igor), Kolcic, I. (Ivana), Navarro, P. (Pau), Zemunik, T. (Tatijana), Salomaa, V. (Veikko), Kooner, J.S. (Jaspal), Kooner, J.S. (Jaspal S.), Lehne, B. (Benjamin), Scott, W.R. (William R.), Tan, S.-T. (Sian-Tsung), Geus, E.J.C. (Eco) de, Milaneschi, Y. (Yuri), Penninx, B.W.J.H. (Brenda), Willemsen, G.A.H.M. (Gonneke), Mutsert, R. (Reneé) de, Ford, I. (Ian), Gansevoort, R.T. (Ron), Segura-Lepe, M.P. (Marcelo P.), Raitakari, O.T. (Olli T.), Viikari, J. (Jorma), Nikus, K. (Kjell), Forrester, T. (Terrence), McKenzie, C.A. (Colin), Craen, A.J. (Anton) de, de Ruijter, H.M. (Hester M.), Pasterkamp, G. (Gerard), Snieder, H. (Harold), Oldehinkel, A.J. (Albertine), Slagboom, P.E. (Eline), Cooper, R.S. (Richard S.), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Elliott, P. (Paul), Harst, P. (Pim) van der, Jukema, J.W. (Jan Wouter), Mook-Kanamori, D.O. (Dennis), Boomsma, D.I. (Dorret), Chambers, J.C. (John C.), Swertz, M. (Morris), Ripatti, S. (Samuli), Willems van Dijk, J.A.P. (Ko), Vitart, V. (Veronique), Polasek, O. (Ozren), Hayward, C. (Caroline), Wilson, J.G. (James G.), Wilson, J.F. (James F), Gudnason, V. (Vilmundur), Rich, S.S. (Stephen), Psaty, B.M. (Bruce), Borecki, I.B. (Ingrid), Boerwinkle, E. (Eric), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), Duijn, C.M. (Cornelia) van, Leeuwen, E.M. (Elisa) van, Sabo, A. (Aniko), Bis, J.C. (Joshua), Huffman, J.E. (Jennifer), Manichaikul, A. (Ani), Smith, A.V. (Davey), Feitosa, M.F. (Mary Furlan), Demissie, S. (Serkalem), Joshi, P.K. (Peter), Duan, Q. (Qing), Marten, J. (Jonathan), Klinken, J.B. (Jan Bert) van, Surakka, I. (Ida), Nolte, I.M. (Ilja), Zhang, W. (Weihua), Mbarek, H., Li-Gao, R. (Ruifang), Trompet, S. (Stella), Verweij, N. (Niek), Evangelou, E. (Evangelos), Lyytikäinen, L.-P. (Leo-Pekka), Tayo, B. (Bamidele), Deelen, J. (Joris), Most, P.J. (Peter) van der, Van Der Laan, S.W. (Sander W.), Arking, D.E. (Dan E.), Morrison, A. (Alanna), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Sijbrands, E.J.G. (Eric), Uitterlinden, A.G. (André), Mychaleckyj, J.C. (Josyf), Campbell, A. (Archie), Hocking, L.J. (Lynne), Padmanabhan, S. (Sandosh), Brody, J.A. (Jennifer A.), Rice, K.M. (Kenneth), White, C.C. (Charles), Harris, T.B. (Tamara), Isaacs, A.J. (Aaron), Campbell, H. (Harry), Lange, L.A. (Leslie), Rudan, I. (Igor), Kolcic, I. (Ivana), Navarro, P. (Pau), Zemunik, T. (Tatijana), Salomaa, V. (Veikko), Kooner, J.S. (Jaspal), Kooner, J.S. (Jaspal S.), Lehne, B. (Benjamin), Scott, W.R. (William R.), Tan, S.-T. (Sian-Tsung), Geus, E.J.C. (Eco) de, Milaneschi, Y. (Yuri), Penninx, B.W.J.H. (Brenda), Willemsen, G.A.H.M. (Gonneke), Mutsert, R. (Reneé) de, Ford, I. (Ian), Gansevoort, R.T. (Ron), Segura-Lepe, M.P. (Marcelo P.), Raitakari, O.T. (Olli T.), Viikari, J. (Jorma), Nikus, K. (Kjell), Forrester, T. (Terrence), McKenzie, C.A. (Colin), Craen, A.J. (Anton) de, de Ruijter, H.M. (Hester M.), Pasterkamp, G. (Gerard), Snieder, H. (Harold), Oldehinkel, A.J. (Albertine), Slagboom, P.E. (Eline), Cooper, R.S. (Richard S.), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Elliott, P. (Paul), Harst, P. (Pim) van der, Jukema, J.W. (Jan Wouter), Mook-Kanamori, D.O. (Dennis), Boomsma, D.I. (Dorret), Chambers, J.C. (John C.), Swertz, M. (Morris), Ripatti, S. (Samuli), Willems van Dijk, J.A.P. (Ko), Vitart, V. (Veronique), Polasek, O. (Ozren), Hayward, C. (Caroline), Wilson, J.G. (James G.), Wilson, J.F. (James F), Gudnason, V. (Vilmundur), Rich, S.S. (Stephen), Psaty, B.M. (Bruce), Borecki, I.B. (Ingrid), Boerwinkle, E. (Eric), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), and Duijn, C.M. (Cornelia) van

Abstract

Background So far, more than 170 loci have been associated with circulating lipid levels through genomewide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ~60 000 individuals in the discovery stage and ~90 000 samples in the replication stage. Results Our study resul

Published
2016
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118. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author

Kilpelainen, TO, Carli, J F M, Skowronski, A A, Sun, Q, Kriebel, J, Feitosa, MF, Hedman, AK, Drong, AW, Hayes, J E, Zhao, JH, Pers, TH, Schick, U, Grarup, N, Kutalik, Z, Trompet, S, Mangino, M, Kristiansson, K, Beekman, M, Lyytikainen, LP, Eriksson, J, Henneman, Peter, Lahti, J, Tanaka, T, Luan, JA, Del Greco, F, Pasko, D, Renstrom, F, Willems, SM, Mahajan, A, Rose, LM, Guo, XQ, Liu, YM, Kleber, ME, Perusse, L, Gaunt, T, Ahluwalia, TS, Sung, YJ, Ramos, YF, Amin, Najaf, Amuzu, A, Barroso, I, Bellis, C, Blangero, J, Buckley, BM, Bohringer, S, Chen, YDI, de Craen, A J N, Crosslin, DR, Dale, CE, Dastani, Z, Day, FR, Deelen, J, Delgado, GE, Demirkan, Ayse, Finucane, FM, Ford, I, Garcia, ME, Gieger, C, Gustafsson, S, Hallmans, G, Hankinson, SE, Havulinna, AS, Herder, Cindy, Hernandez, D, Hicks, AA, Hunter, DJ, Illig, T, Ingelsson, E, Ioan-Facsinay, A, Jansson, JO, Jenny, NS, Jorgensen, ME, Jorgensen, T, Karlsson, M, Koenig, W, Kraft, P, Kwekkeboom, J, Laatikainen, T, Ladwig, KH, LeDuc, C A, Lowe, G, Lu, YC, Marques-Vidal, P, Meisinger, C, Menni, C, Morris, AP, Myers, RH, Mannisto, S, Nalls, MA, Paternoster, L, Peters, A, Pradhan, A D, Rankinen, T, Rasmussen-Torvik, LJ, Rathmann, W, Rice, TK, Richards, JB, Ridker, PM, Sattar, N, Savage, DB, Soderberg, S, Timpson, NJ, Vandenput, L, van Heemst, D, Uh, HW, Vohl, MC, Walker, M, Wichmann, HE, Widen, E, Wood, AR, Yao, J, Zeller, T, Zhang, YY, Meulenbelt, I, Kloppenburg, M, Astrup, A, Sorensen, TIA, Sarzynski, MA, Rao, DC, Jousilahti, P, Vartiainen, E, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Kajantie, E, Osmond, C, Palotie, A, Eriksson, JG, Heliovaara, M, Knekt, PB, Koskinen, S, Jula, A, Perola, M, Huupponen, R K, Viikari, JS, Kahonen, M, Lehtimaki, T, Raitakari, OT, Mellstrom, D, Lorentzon, M, Casas, JP, Bandinelli, S, Marz, W, Isaacs, Aaron, van Dijk, KW, Duijn, Cornelia, Harris, TB, Bouchard, C, Allison, MA, Chasman, DI, Ohlsson, C, Lind, L, Scott, RA, Langenberg, C, Wareham, NJ, Ferrucci, L, Frayling, TM, Pramstaller, PP, Borecki, IB, Waterworth, DM, Bergmann, S, Waeber, G, Vollenweider, P, Vestergaard, H, Hansen, T, Pedersen, O, Hu, FB, Slagboom, PE (Eline), Grallert, H, Spector, TD, Jukema, JW, Klein, RJ, Schadt, EE, Franks, PW, Lindgren, CM, Leibel, R L, Loos, RJF, Kilpelainen, TO, Carli, J F M, Skowronski, A A, Sun, Q, Kriebel, J, Feitosa, MF, Hedman, AK, Drong, AW, Hayes, J E, Zhao, JH, Pers, TH, Schick, U, Grarup, N, Kutalik, Z, Trompet, S, Mangino, M, Kristiansson, K, Beekman, M, Lyytikainen, LP, Eriksson, J, Henneman, Peter, Lahti, J, Tanaka, T, Luan, JA, Del Greco, F, Pasko, D, Renstrom, F, Willems, SM, Mahajan, A, Rose, LM, Guo, XQ, Liu, YM, Kleber, ME, Perusse, L, Gaunt, T, Ahluwalia, TS, Sung, YJ, Ramos, YF, Amin, Najaf, Amuzu, A, Barroso, I, Bellis, C, Blangero, J, Buckley, BM, Bohringer, S, Chen, YDI, de Craen, A J N, Crosslin, DR, Dale, CE, Dastani, Z, Day, FR, Deelen, J, Delgado, GE, Demirkan, Ayse, Finucane, FM, Ford, I, Garcia, ME, Gieger, C, Gustafsson, S, Hallmans, G, Hankinson, SE, Havulinna, AS, Herder, Cindy, Hernandez, D, Hicks, AA, Hunter, DJ, Illig, T, Ingelsson, E, Ioan-Facsinay, A, Jansson, JO, Jenny, NS, Jorgensen, ME, Jorgensen, T, Karlsson, M, Koenig, W, Kraft, P, Kwekkeboom, J, Laatikainen, T, Ladwig, KH, LeDuc, C A, Lowe, G, Lu, YC, Marques-Vidal, P, Meisinger, C, Menni, C, Morris, AP, Myers, RH, Mannisto, S, Nalls, MA, Paternoster, L, Peters, A, Pradhan, A D, Rankinen, T, Rasmussen-Torvik, LJ, Rathmann, W, Rice, TK, Richards, JB, Ridker, PM, Sattar, N, Savage, DB, Soderberg, S, Timpson, NJ, Vandenput, L, van Heemst, D, Uh, HW, Vohl, MC, Walker, M, Wichmann, HE, Widen, E, Wood, AR, Yao, J, Zeller, T, Zhang, YY, Meulenbelt, I, Kloppenburg, M, Astrup, A, Sorensen, TIA, Sarzynski, MA, Rao, DC, Jousilahti, P, Vartiainen, E, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Kajantie, E, Osmond, C, Palotie, A, Eriksson, JG, Heliovaara, M, Knekt, PB, Koskinen, S, Jula, A, Perola, M, Huupponen, R K, Viikari, JS, Kahonen, M, Lehtimaki, T, Raitakari, OT, Mellstrom, D, Lorentzon, M, Casas, JP, Bandinelli, S, Marz, W, Isaacs, Aaron, van Dijk, KW, Duijn, Cornelia, Harris, TB, Bouchard, C, Allison, MA, Chasman, DI, Ohlsson, C, Lind, L, Scott, RA, Langenberg, C, Wareham, NJ, Ferrucci, L, Frayling, TM, Pramstaller, PP, Borecki, IB, Waterworth, DM, Bergmann, S, Waeber, G, Vollenweider, P, Vestergaard, H, Hansen, T, Pedersen, O, Hu, FB, Slagboom, PE (Eline), Grallert, H, Spector, TD, Jukema, JW, Klein, RJ, Schadt, EE, Franks, PW, Lindgren, CM, Leibel, R L, and Loos, RJF

Published
2016

119. Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms

Author

Slieker, R C, van Iterson, M, Luijk, R, Beekman, M, Zhernakova, DV, Moed, MH, Mei, H L, van Galen, M, Deelen, P, Bonder, MJ, Zhernakova, A, Uitterlinden, André, Tigchelaar, E F, Stehouwer, CDA, Schalkwijk, CG, van der Kallen, CJH, Hofman, Bert, van Heemst, D, de Geus, EJ, Dongen, J, Deelen, J, van den Berg, LH, van Meurs, Joyce, Jansen, R, 't Hoen, PAC, Franke, L, Wijmenga, C, Veldink, JH, Swertz, MA, van Greevenbroek, MMJ, Duijn, Cornelia, Boomsma, DI, Slagboom, PE (Eline), Heijmans, BT, Slieker, R C, van Iterson, M, Luijk, R, Beekman, M, Zhernakova, DV, Moed, MH, Mei, H L, van Galen, M, Deelen, P, Bonder, MJ, Zhernakova, A, Uitterlinden, André, Tigchelaar, E F, Stehouwer, CDA, Schalkwijk, CG, van der Kallen, CJH, Hofman, Bert, van Heemst, D, de Geus, EJ, Dongen, J, Deelen, J, van den Berg, LH, van Meurs, Joyce, Jansen, R, 't Hoen, PAC, Franke, L, Wijmenga, C, Veldink, JH, Swertz, MA, van Greevenbroek, MMJ, Duijn, Cornelia, Boomsma, DI, Slagboom, PE (Eline), and Heijmans, BT

Published
2016

120. Blood lipids influence DNA methylation in circulating cells

Author

Dekkers, K F, van Iterson, M, Slieker, R C, Moed, MH, Bonder, MJ, van Galen, M, Mei, H L, Zhernakova, DV, van den Berg, LH, Deelen, J, Dongen, J, van Heemst, D, Hofman, Bert, Hottenga, JJ, van der Kallen, CJH, Schalkwijk, CG, Stehouwer, CDA, Tigchelaar, E F, Uitterlinden, André, Willemsen, G, Zhernakova, A, Franke, L, 't Hoen, PAC, Jansen, R, van Meurs, Joyce, Boomsma, DI, Duijn, Cornelia, van Greevenbroek, MMJ, Veldink, JH, Wijmenga, C, van Zwet, EW, Slagboom, PE (Eline), Jukema, JW, Heijmans, BT, Dekkers, K F, van Iterson, M, Slieker, R C, Moed, MH, Bonder, MJ, van Galen, M, Mei, H L, Zhernakova, DV, van den Berg, LH, Deelen, J, Dongen, J, van Heemst, D, Hofman, Bert, Hottenga, JJ, van der Kallen, CJH, Schalkwijk, CG, Stehouwer, CDA, Tigchelaar, E F, Uitterlinden, André, Willemsen, G, Zhernakova, A, Franke, L, 't Hoen, PAC, Jansen, R, van Meurs, Joyce, Boomsma, DI, Duijn, Cornelia, van Greevenbroek, MMJ, Veldink, JH, Wijmenga, C, van Zwet, EW, Slagboom, PE (Eline), Jukema, JW, and Heijmans, BT

Published
2016

121. Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

Author

Leeuwen, Elisa, Sabo, A, Bis, JC, Huffman, JE, Manichaikul, A, Smith, AV, Feitosa, MF, Demissie, S, Joshi, PK, Duan, Q, Marten, J, van Klinken, JB, Surakka, I, Nolte, IM, Zhang, WH, Mbarek, H, Li-Gao, RF, Trompet, S, Verweij, N, Evangelou, E, Lyytikainen, LP, Tayo, BO, Deelen, J, van der Most, PJ, van der Laan, SW, Arking, DE, Morrison, A, Dehghan, Abbas, Franco Duran, OH, Hofman, Bert, Rivadeneira, Fernando, Sijbrands, E.J.G., Uitterlinden, André, Mychaleckyj, JC, Campbell, A (Archie), Hocking, LJ, Padmanabhan, S, Brody, JA, Rice, KM, White, CC, Harris, T, Isaacs, Aaron, Campbell, H, Lange, LA, Rudan, I, Kolcic, I, Navarro, P, Zemunik, T, Salomaa, V, Kooner, AS, Kooner, JS, Lehne, B, Scott, WR, Tan, ST, de Geus, EJ, Milaneschi, Y, Penninx, BWJH, Willemsen, G, de Mutsert, R, Ford, I, Gansevoort, RT, Segura-Lepe, M P, Raitakari, OT, Viikari, JS, Nikus, K, Forrester, T, McKenzie, CA, de Craen, AJM, den Ruijter, HM, Pasterkamp, G, Snieder, H, Oldehinkel, AJ, Slagboom, PE (Eline), Cooper, RS, Kahonen, M, Lehtimaki, T, Elliott, P, van der Harst, P, Jukema, JW, Mook-Kanamori, DO, Boomsma, DI, Chambers, JC, Swertz, M, Ripatti, S, van Dijk, KW, Vitart, V, Polasek, O, Hayward, C, Wilson, JG, Wilson, JF, Gudnason, V, Rich, SS, Psaty, BM, Borecki, IB, Boerwinkle, E, Rotter, JI, Cupples, LA, Duijn, Cornelia, Leeuwen, Elisa, Sabo, A, Bis, JC, Huffman, JE, Manichaikul, A, Smith, AV, Feitosa, MF, Demissie, S, Joshi, PK, Duan, Q, Marten, J, van Klinken, JB, Surakka, I, Nolte, IM, Zhang, WH, Mbarek, H, Li-Gao, RF, Trompet, S, Verweij, N, Evangelou, E, Lyytikainen, LP, Tayo, BO, Deelen, J, van der Most, PJ, van der Laan, SW, Arking, DE, Morrison, A, Dehghan, Abbas, Franco Duran, OH, Hofman, Bert, Rivadeneira, Fernando, Sijbrands, E.J.G., Uitterlinden, André, Mychaleckyj, JC, Campbell, A (Archie), Hocking, LJ, Padmanabhan, S, Brody, JA, Rice, KM, White, CC, Harris, T, Isaacs, Aaron, Campbell, H, Lange, LA, Rudan, I, Kolcic, I, Navarro, P, Zemunik, T, Salomaa, V, Kooner, AS, Kooner, JS, Lehne, B, Scott, WR, Tan, ST, de Geus, EJ, Milaneschi, Y, Penninx, BWJH, Willemsen, G, de Mutsert, R, Ford, I, Gansevoort, RT, Segura-Lepe, M P, Raitakari, OT, Viikari, JS, Nikus, K, Forrester, T, McKenzie, CA, de Craen, AJM, den Ruijter, HM, Pasterkamp, G, Snieder, H, Oldehinkel, AJ, Slagboom, PE (Eline), Cooper, RS, Kahonen, M, Lehtimaki, T, Elliott, P, van der Harst, P, Jukema, JW, Mook-Kanamori, DO, Boomsma, DI, Chambers, JC, Swertz, M, Ripatti, S, van Dijk, KW, Vitart, V, Polasek, O, Hayward, C, Wilson, JG, Wilson, JF, Gudnason, V, Rich, SS, Psaty, BM, Borecki, IB, Boerwinkle, E, Rotter, JI, Cupples, LA, and Duijn, Cornelia

Published
2016

122. Novel loci and pathways significantly associated with longevity.

Author

Zeng, Y, Nie, C, Min, J, Liu, X, Li, M, Chen, H, Xu, H, Wang, M, Ni, T, Li, Y, Yan, H, Zhang, J-P, Song, C, Chi, L-Q, Wang, H-M, Dong, J, Zheng, G-Y, Lin, L, Qian, F, Qi, Y, Cao, H, Wang, Y, Zhang, L, Li, Z, Zhou, Y, Lu, J, Li, J, Qi, M, Bolund, L, Yashin, A, Land, KC, Gregory, S, Yang, Z, Gottschalk, W, Tao, W, Wang, J, Xu, X, Bae, H, Nygaard, M, Christiansen, L, Christensen, K, Franceschi, C, Lutz, MW, Gu, J, Tan, Q, Perls, T, Sebastiani, P, Deelen, J, Slagboom, E, Hauser, E, Tian, X-L, Yang, H, Vaupel, JW, Zeng, Y, Nie, C, Min, J, Liu, X, Li, M, Chen, H, Xu, H, Wang, M, Ni, T, Li, Y, Yan, H, Zhang, J-P, Song, C, Chi, L-Q, Wang, H-M, Dong, J, Zheng, G-Y, Lin, L, Qian, F, Qi, Y, Cao, H, Wang, Y, Zhang, L, Li, Z, Zhou, Y, Lu, J, Li, J, Qi, M, Bolund, L, Yashin, A, Land, KC, Gregory, S, Yang, Z, Gottschalk, W, Tao, W, Wang, J, Xu, X, Bae, H, Nygaard, M, Christiansen, L, Christensen, K, Franceschi, C, Lutz, MW, Gu, J, Tan, Q, Perls, T, Sebastiani, P, Deelen, J, Slagboom, E, Hauser, E, Tian, X-L, Yang, H, and Vaupel, JW

Abstract

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.

Published
2016

123. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited

Author

Deelen J., Beekman M., Uh H. -W., Helmer Q., Kuningas M., Christiansen L., Kremer D., van der Breggen R., Suchiman H. E. D., Lakenberg N., van den Akker E. B., Passtoors W. M., Tiemeier H., van Heemst D., de Craen A. J., Rivadeneira F., de Geus E. J., Perola M., van der Ouderaa F. J., Gunn D. A., Boomsma D. I., Uitterlinden A. G., Christensen K., van Duijn C. M., Heijmans B. T., Houwing-Duistermaat J. J., Westendorp R. G. J., Slagboom P. E., Epidemiology, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Biological Psychology, EMGO+ - Mental Health, Deelen J., Beekman M., Uh H.-W., Helmer Q., Kuningas M., Christiansen L., Kremer D., van der Breggen R., Suchiman H.E.D., Lakenberg N., van den Akker E.B., Passtoors W.M., Tiemeier H., van Heemst D., de Craen A.J., Rivadeneira F., de Geus E.J., Perola M., van der Ouderaa F.J., Gunn D.A., Boomsma D.I., Uitterlinden A.G., Christensen K., van Duijn C.M., Heijmans B.T., Houwing-Duistermaat J.J., Westendorp R.G.J., and Slagboom P.E.

Subjects
Adult, Male, Netherlands Twin Register (NTR), Longevity, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Cohort Studies, Apolipoproteins E, Genetic, SDG 3 - Good Health and Well-being, Alzheimer Disease, Humans, Genetic Predisposition to Disease, genetics, Longitudinal Studies, human, Aged, apolipoprotein E, Aged, 80 and over, genome-wide association study, Genome, Human, Forkhead Box Protein O3, aging, Forkhead Transcription Factors, Original Articles, aging apolipoprotein E genetics genome-wide association study human longevity apolipoprotein-e genotype growth-factor-i human longevity leiden longevity familial longevity alzheimers-disease nonagenarian siblings exceptional longevity depressive disorder artery-disease, Middle Aged, humanities, Genetic Loci, Case-Control Studies, Female, Proto-Oncogene Proteins c-akt
Abstract

By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Study (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study, and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P

Published
2011

124. Genetic and biomarker studies of human longevity

Author

Deelen, J., Slagboom, P., Westendorp, R.G.J., Beekman, M., and Leiden University

Subjects
Genome-wide association study, Aging, Gene set analysis, Prospective mortality, Longevity, Genetics, Biomarker, Leukocyte telomere length
Abstract

The aim of this thesis was to identify novel lifespan regulating loci that influence human longevity and population mortality. To this end, we performed two genome-wide association studies, one of long-lived individuals from the family-based Leiden Longevity Study (LLS) and an extended one of long-lived individuals from multiple cohorts of European descent. Using the latter, we identified two genome-wide significant loci, the TOMM40/APOE/APOC1 locus and an intergenic locus on chromosome 5q33.3. In addition, our gene set analysis with the LLS data showed that genetic variation in genes involved in the insulin/IGF-1 signaling and telomere maintenance pathways is associated with human longevity. Since our genetic studies identified a limited number of longevity loci, we additionally examined whether leukocyte telomere length (LTL) could be used as a biomarker of healthy aging. We showed that LTL meets three of the four criteria for a biomarker of healthy aging in the LLS, i.e., LTL changes with chronological age and is associated with health, in this case immune-related parameters, and prospective mortality. To identify novel longevity loci, future research may benefit from a better definition of the healthy aging phenotype, combining study designs, and the use of novel methods and technologies, such as next-generation sequencing.

Published
2014

125. Optical characteristics of thin CIGS cells on TCO back contact

Author

Van Deelen, J., Kniknie, B., Vroon, Z., Würz, R., and Kessler, F.

Subjects
TS - Technical Sciences, Industrial Innovation, THIN FILM SOLAR CELLS, TFT - Thin Film Technology, Mechanics, Materials and Structures, CdTe, CIS and Related Ternary and Quaternary Thin Film Solar Cells, sense organs, PV, CIGS, Materials
Abstract

29th European Photovoltaic Solar Energy Conference and Exhibition; 1701-1703, Reduction of CIGS layer thickness could translate in significant cost reduction. CIGS was made on transparent conductive oxide (TCO) to allow for optical characterization. This data was compared with external quantum efficiency (EQE) data. The results suggest that changes in surface morphology are an important aspect, which has to be taken into account when interpreting the data for thin CIGS cells in conjunction with the effects of reduced absorption associated with thin CIGS layers. EQE with back side illumination suggests that bulk recombination will lead to less than optimal functionality of light management technology implemented at the back side of the cell.

Published
2014

127. Novel susceptability loci for osteoarthritis of the hand: Coding variants in MGP and ENPP3

Author

den Hollander, W., primary, Boer, C.G., additional, Hart, D., additional, Yau, M.S., additional, Ramos, Y.F., additional, Metrustry, S., additional, Broer, L., additional, Deelen, J., additional, Beekman, M., additional, Cupples, L.A., additional, Rivadeneira, F., additional, Kloppenburg, M., additional, Peters, M., additional, Spector, T.D., additional, Hofman, A., additional, Slagboom, P.E., additional, Nelissen, R.G., additional, Uitterlinden, A.G., additional, Felson, D.T., additional, Valdes, A., additional, Meulenbelt, I., additional, and van Meurs, J.J., additional

Published
2016
Full Text
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128. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

Leeuwen, E.M. van, Karssen, L.C., Deelen, J., Isaacs, A., Medina-Gomez, C., Mbarek, H., Kanterakis, A., Trompet, S., Postmus, I., Verweij, N., Enckevort, D.J. van, Huffman, J.E., White, C.C., Feitosa, M.F., Bartz, T.M., Manichaikul, A., Joshi, P.K., Peloso, G.M., Deelen, P., Dijk, F. van, Willemsen, G., Geus, E.J. de, Milaneschi, Y., Penninx, B.W., Francioli, L.C., Menelaou, A., Pulit, S.L., Rivadeneira, F., Hofman, A., Oostra, B.A., Franco, O.H., Leach, I. Mateo, Beekman, M., Craen, A.J. de, Uh, H.W., Trochet, H., Hocking, L.J., Porteous, D.J., Sattar, N., Packard, C.J., Buckley, B.M., Brody, J.A., Bis, J.C., Rotter, J.I., Mychaleckyj, J.C., Campbell, H., Duan, Q., Lange, L.A., Wilson, J.F., Hayward, C., Polasek, O., Vitart, V., Rudan, I., Wright, A.F., Rich, S.S., Psaty, B.M., Borecki, I.B., Kearney, P.M., Stott, D.J., Cupples, L. Adrienne, Consortium, G.o.t.N., Jukema, J.W., Harst, P. van der, Sijbrands, E.J., Hottenga, J.J., Uitterlinden, A.G., Swertz, M.A., Ommen, G.J. van, Bakker, P.I. de, Slagboom, P., Boomsma, D.I., Wijmenga, C., Duijn, C.M. van, Hehir-Kwa, J.Y., et al., Leeuwen, E.M. van, Karssen, L.C., Deelen, J., Isaacs, A., Medina-Gomez, C., Mbarek, H., Kanterakis, A., Trompet, S., Postmus, I., Verweij, N., Enckevort, D.J. van, Huffman, J.E., White, C.C., Feitosa, M.F., Bartz, T.M., Manichaikul, A., Joshi, P.K., Peloso, G.M., Deelen, P., Dijk, F. van, Willemsen, G., Geus, E.J. de, Milaneschi, Y., Penninx, B.W., Francioli, L.C., Menelaou, A., Pulit, S.L., Rivadeneira, F., Hofman, A., Oostra, B.A., Franco, O.H., Leach, I. Mateo, Beekman, M., Craen, A.J. de, Uh, H.W., Trochet, H., Hocking, L.J., Porteous, D.J., Sattar, N., Packard, C.J., Buckley, B.M., Brody, J.A., Bis, J.C., Rotter, J.I., Mychaleckyj, J.C., Campbell, H., Duan, Q., Lange, L.A., Wilson, J.F., Hayward, C., Polasek, O., Vitart, V., Rudan, I., Wright, A.F., Rich, S.S., Psaty, B.M., Borecki, I.B., Kearney, P.M., Stott, D.J., Cupples, L. Adrienne, Consortium, G.o.t.N., Jukema, J.W., Harst, P. van der, Sijbrands, E.J., Hottenga, J.J., Uitterlinden, A.G., Swertz, M.A., Ommen, G.J. van, Bakker, P.I. de, Slagboom, P., Boomsma, D.I., Wijmenga, C., Duijn, C.M. van, Hehir-Kwa, J.Y., and et al.

Abstract

Contains fulltext : 155355.pdf (publisher's version ) (Open Access)

Published
2015

129. New genetic loci link adipose and insulin biology to body fat distribution.

Author

ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., Carlson, OD., Egan, JM., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, ML., Loo, BM., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, HE., Deloukas, P., Katsareli, E., Couper, DJ., Duncan, BB., Kloppenburg, M., Adair, LS., Borja, JB., Wilson, JG., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, TM., Allison, MA., Redline, S., Buxbaum, SG., Mohlke, KL., Meulenbelt, I., Ballantyne, CM., Dedoussis, GV., Hu, FB., Liu, Y., Paulweber, B., Spector, TD., Slagboom, P., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, JC., Salomaa, V., Eriksson, JG., Frayling, TM., Hicks, AA., Lehtimäki, T., Smith, GD., Siscovick, DS., Kronenberg, F., van Duijn, C., Loos, RJ., Waterworth, DM., Meigs, JB., Dupuis, J., Richards, JB., Willenborg, C., Farrall, M., Assimes, TL., Thompson, JR., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, BA., Stirrups, K., König, IR., Cazier, JB., Johansson£££Åsa£££ Å., Hall, AS., Lee, JY., Willer, CJ., Chambers, JC., Esko£££Tõnu£££ T., Folkersen, L., Goel, A., Grundberg, E., Havulinna, AS., Ho, WK., Hopewell, JC., Eriksson, N., Kleber, ME., Lundmark, P., Lyytikäinen, LP., Rafelt, S., Shungin, D., Strawbridge, RJ., Thorleifsson, G., Tikkanen, E., Van Zuydam, N., Voight, BF., Waite, LL., Zhang, W., Ziegler, A., Absher, D., Altshuler, D., Balmforth, AJ., Barroso£££Inês£££ I., Braund, PS., Burgdorf, C., Claudi-Boehm, S., Cox, D., Dimitriou, M., Do, R., Doney, AS., El Mokhtari, N., Eriksson, P., Fischer, K., Fontanillas, P., Franco-Cereceda, A., Gigante, B., Groop, L., Gustafsson, S., Hager, J., Hallmans, G., Han, BG., Hunt, SE., Kang, HM., Illig, T., Kessler, T., Knowles, JW., Kolovou, G., Kuusisto, J., Langford, C., Leander, K., Lokki, ML., Lundmark, A., McCarthy, MI., Meisinger, C., Melander, O., Mihailov, E., Maouche, S., Morris, AD., Müller-Nurasyid, M., Nikus, K., Peden, JF., Rayner, NW., Rasheed, A., Rosinger, S., Rubin, D., Rumpf, MP., Schäfer, A., Sivananthan, M., Song, C., Stewart, AF., Tan, ST., Thorgeirsson, G., van der Schoot CE., Wagner, PJ., Wells, GA., Wild, PS., Yang, TP., Amouyel, P., Arveiler, D., Basart, H., Boehnke, M., Boerwinkle, E., Brambilla, P., Cambien, F., Cupples, AL., de Faire, U., Dehghan, A., Diemert, P., Epstein, SE., Evans, A., Ferrario, MM., Ferrières, J., Gauguier, D., Go, AS., Goodall, AH., Gudnason, V., Hazen, S., Holm, H., Iribarren, C., Jang, Y., Kee, F., Kim, HS., Koenig, W., Kratzer, W., Kuulasmaa, K., Laakso, M., Laaksonen, R., Lind, L., Ouwehand, WH., Parish, S., Park, JE., Pedersen, NL., Peters, A., Quertermous, T., Rader, DJ., Schadt, E., Shah, SH., Sinisalo, J., Stark, K., Stefansson, K., Trégouët, DA., Virtamo, J., Wallentin, L., Wareham, N., Zimmermann, ME., Nieminen, MS., Hengstenberg, C., Sandhu, MS., Pastinen, T., Syvänen, AC., Hovingh, GK., Dedoussis, G., Franks, PW., Metspalu, A., Zalloua, PA., Siegbahn, A., Schreiber, S., Ripatti, S., Blankenberg, SS., Clarke, R., Boehm, BO., O'Donnell, C., Reilly, MP., März, W., Collins, R., Kathiresan, S., Hamsten, A., Kooner, JS., Thorsteinsdottir, U., Danesh, J., Palmer, CN., Roberts, R., Watkins, H., Schunkert, H., Samani, NJ., Pattaro, C., Köttgen, A., Teumer, A., Garnaas, M., Böger, CA., Olden, M., Chen, MH., Tin, A., Taliun, D., Li, M., Gao, X., Gorski, M., Yang, Q., Hundertmark, C., Foster, MC., O'Seaghdha, CM., Glazer, N., Smith, AV., O'Connell, JR., Struchalin, M., Li, G., Johnson, AD., Gierman, HJ., Feitosa, M., Hwang, SJ., Atkinson, EJ., Cornelis, MC., Tönjes, A., Chouraki, V., Holliday, EG., Sorice, R., Kutalik, Z., Deshmukh, H., Ulivi, S., Chu, AY., Murgia, F., Trompet, S., Imboden, M., Kollerits, B., Pistis, G., Harris, TB., Launer, LJ., Aspelund, T., Eiriksdottir, G., Mitchell, BD., Schmidt, H., Cavalieri, M., Rao, M., Demirkan, A., de Andrade, M., Turner, ST., Ding, J., Andrews, JS., Freedman, BI., Döring, A., Wichmann, H-., Kolcic, I., Zemunik, T., Boban, M., Minelli, C., Wheeler, HE., Igl, W., Zaboli, G., Wild, SH., Wright, AF., Campbell, H., Ellinghaus, D., Nöthlings, U., Jacobs, G., Biffar, R., Endlich, K., Ernst, F., Homuth, G., Kroemer, HK., Nauck, M., Stracke, S., Völker, U., Völzke, H., Kovacs, P., Stumvoll, M., Mägi, R., Hofman, A., Uitterlinden, AG., Rivadeneira, F., Aulchenko, YS., Polasek, O., Hastie, N., Vitart, V., Helmer, C., Wang, JJ., Ruggiero, D., Bergmann, S., Nikopensius, T., Province, M., Ketkar, S., Colhoun, H., Doney, A., Robino, A., Giulianini, F., Krämer, BK., Portas, L., Ford, I., Buckley, BM., Adam, M., Thun, GA., Sala, C., Metzger, M., Mitchell, P., Ciullo, M., Kim, SK., Palmer, C., Gasparini, P., Pirastu, M., Jukema, JW., Probst-Hensch, NM., Toniolo, D., Shuldiner, AR., Coresh, J., Schmidt, R., van Duijn CM., Borecki, I., Kardia, SL., Curhan, GC., Rudan, I., Gyllensten, U., Wilson, JF., Franke, A., Rettig, R., Prokopenko, I., Witteman, JC., Hayward, C., Ridker, P., Parsa, A., Bochud, M., Goessling, W., Chasman, DI., Kao, W., Fox, CS., de Boer IH., Glazer, NL., Peralta, CA., Kutalik£££Zoltán£££ Z., 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NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Winkler, T.W., Croteau-Chonka, D.C., Locke, A.E., Strawbridge, R.J., Pers, T.H., Justice, A.E., Workalemahu, T., Wu, J.M., Buchkovich, M.L., Heard-Costa, N.L., Roman, T.S., Drong, A.W., Day, F.R., Luan, J., Randall, J.C., Scherag, A., Wood, A.R., Fehrmann, R., Karjalainen, J., Kahali, B., Liu, C.T., Schmidt, E.M., Anderson, D., Bragg-Gresham, J.L., Ehret, G.B., Feitosa, M.F., Jackson, A.U., Kleber, M.E., Mateo Leach, I., Medina-Gomez, C., Palmer, C.D., Pasko, D., Pechlivanis, S., Peters, M.J., Ju Sung, Y., Van Vliet-Ostaptchouk, J.V., Yengo, L., Arscott, G.M., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bonnet, F., Böttcher, Y., Carba, D.B., Caspersen, I.H., Daw, E.W., Deelen, J., Delgado, G., Doney, A.S., Eklund, N., Erdos, M.R., Eury, E., Friedrich, N., Garcia, M.E., Giedraitis, V., Go, A.S., Golay, A., Grammer, T.B., Gräßler, J., Grewal, J., Groves, C.J., Hartman, C.A., Hassinen, M., Herzig, K.H., Helmer, Q., Hillege, H.L., Holmen, O., Hunt, S.C., Ittermann, T., James, A.L., Johansson, I., Juliusdottir, T., Kalafati, I.P., Kinnunen, L., Kooner, I.K., Lee, N.R., Lichtner, P., Lobbens, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Mills, R., Monda, K.L., Mooijaart, S.P., Mühleisen, T.W., Mulas, A., Nalls, M.A., Glorioso, N., Nolte, I.M., Rayner, N.W., Renstrom, F., Ried, J.S., Robertson, N.R., Rose, L.M., Scholtens, S., Seufferlein, T., Sitlani, C.M., Vernon Smith, A., Stringham, H.M., Sundström, J., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tayo, B.O., Tomaschitz, A., Troffa, C., van Oort, F.V., Vonk, J.M., Waite, L.L., Wennauer, R., Wojczynski, M.K., Zhang, Q., Hua Zhao, J., Brennan, E.P., Choi, M., Gharavi, A.G., Hedman, Å.K., Hivert, M.F., Huang, J., Karpe, F., Kiryluk, K., Liang, L., Lifton, R.P., Ma, B., McKnight, A.J., McPherson, R., Min, J.L., Moffatt, M.F., Montgomery, G.W., Murabito, J.M., Nicholson, G., Nyholt, D.R., Olsson, C., Perry, J.R., Reinmaa, E., Salem, R.M., Schadt, E.E., Scott, R.A., Vallejo, E.E., Westra, H.J., Zondervan, K.T., Bakker, S.J., Beilby, J., Bergman, R.N., Blangero, J., Brown, M.J., Chines, P.S., Collins, F.S., Crawford, D.C., de Geus, E.J., Erbel, R., Eriksson, J.G., Ferrannini, E., Forouhi, N.G., Franco, O.H., Gansevoort, R.T., Haiman, C.A., Harris, T.B., Hattersley, A.T., Heliövaara, M., Hicks, A.A., Hingorani, A.D., Hoffmann, W., Humphries, S.E., Jarvelin, M.R., Johansen, B., Jousilahti, P., Jula, A.M., Keinanen-Kiukaanniemi, S.M., Kooner, J.S., Kraja, A.T., Lakka, T.A., Le Marchand, L., Lyssenko, V., Männistö, S., Marette, A., Matise, T.C., McKenzie, C.A., Musk, A.W., Möhlenkamp, S., Morris, A.D., Oldehinkel, A.J., Ong, K.K., Palmer, L.J., Penninx, B.W., Pramstaller, P.P., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Ridker, P.M., Ritchie, M.D., Samani, N.J., Sarzynski, M.A., Schwarz, P.E., Shuldiner, A.R., Staessen, J.A., Steinthorsdottir, V., Stolk, R.P., Strauch, K., Tremblay, A., Vohl, M.C., Wilson, J.F., Witteman, J.C., Adair, L.S., Boehm, B.O., Bornstein, S.R., Bouchard, C., Cauchi, S., Caulfield, M.J., Chambers, J.C., Chasman, D.I., Cooper, R.S., Grabe, H.J., Jöckel, K.H., Munroe, P.B., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Pérusse, L., Saaristo, T.E., Slagboom, P.E., Spector, T.D., Uitterlinden, A.G., Veronesi, G., Walker, M., Wareham, N.J., Wichmann, H.E., Abecasis, G.R., Assimes, T.L., Berndt, S.I., Borecki, I.B., Frayling, T.M., Groop, L.C., Hunter, D.J., Kaplan, R.C., O'Connell, J.R., Strachan, D.P., van Duijn, C.M., Willer, C.J., Visscher, P.M., Yang, J., Hirschhorn, J.N., Zillikens, M.C., McCarthy, M.I., Speliotes, E.K., North, K.E., Fox, C.S., Franks, P.W., Heid, I.M., Loos, R.J., Cupples, L.A., Morris, A.P., Lindgren, C.M., and Mohlke, K.L.

Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Published
2015

130. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), Mohlke, K.L. (Karen), Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), and Mohlke, K.L. (Karen)

Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10-8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Published
2015
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131. The impact of low-frequency and rare variants on lipid levels

Author

Surakka, I. (Ida), Horikoshi, M. (Momoko), Mägi, R. (Reedik), Sarin, A.-P., Mahajan, A. (Anubha), Lagou, V. (Vasiliki), Marullo, L. (Letizia), Ferreira, T. (Teresa), Miraglio, B. (Benjamin), Timonen, S. (Sanna), Kettunen, J. (Johannes), Pirinen, M. (Matti), Karjalainen, J. (Juha), Thorleifsson, G. (Gudmar), Hägg, S. (Sara), Hottenga, J.J. (Jouke Jan), Isaacs, A.J. (Aaron), Ladenvall, C. (Claes), Beekman, M. (Marian), Esko, T. (Tõnu), Ried, J.S. (Janina), Nelson, C.P. (Christopher P.), Willenborg, C. (Christina), Gustafsson, S. (Stefan), Westra, H.J. (Harm-Jan), Blades, M. (Matthew), De Craen, A.J.M. (Anton J. M.), Geus, E.J.C. (Eco) de, Deelen, J. (Joris), Grallert, H. (Harald), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hengstenberg, C. (Christian), Houwing-Duistermaat, J.J. (Jeanine), Hypponen, E. (Elina), Karssen, L.C. (Lennart), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Magnusson, P.K. (Patrik), Mihailov, E. (Evelin), Müller-Nurasyid, M. (Martina), Mpindi, J.-P. (John-Patrick), Pedersen, N.L. (Nancy L.), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pers, T.H. (Tune), Peters, A. (Annette), Rung, J. (Johan), Smit, J.H. (Johannes), Steinthorsdottir, V. (Valgerdur), Tobin, M.D. (Martin), Tsernikova, N. (Natalia), Leeuwen, E.M. (Elisa) van, Viikari, J. (Jorma), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Samani, N.J. (Nilesh), Kaprio, J. (Jaakko), Lind, L. (Lars), Gieger, C. (Christian), Metspalu, A. (Andres), Slagboom, P.E. (Eline), Groop, L. (Leif), Duijn, C.M. (Cornelia) van, Eriksson, J.G. (Johan G.), Jula, A. (Antti), Salomaa, V. (Veikko), Boomsma, D.I. (Dorret), Power, C. (Christopher), Raitakari, O.T. (Olli T.), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Thorsteinsdottir, U. (Unnur), Franke, L. (Lude), Ikonen, E. (Elina), Kallioniemi, O. (Olli), Pietiäinen, V. (Vilja), Lindgren, C.M. (Cecilia M.), Zwart, J-A. (John-Anker), Palotie, A. (Aarno), McCarthy, M.I. (Mark), Morris, A.P. (Andrew), Prokopenko, I. (Inga), Ripatti, S. (Samuli), Surakka, I. (Ida), Horikoshi, M. (Momoko), Mägi, R. (Reedik), Sarin, A.-P., Mahajan, A. (Anubha), Lagou, V. (Vasiliki), Marullo, L. (Letizia), Ferreira, T. (Teresa), Miraglio, B. (Benjamin), Timonen, S. (Sanna), Kettunen, J. (Johannes), Pirinen, M. (Matti), Karjalainen, J. (Juha), Thorleifsson, G. (Gudmar), Hägg, S. (Sara), Hottenga, J.J. (Jouke Jan), Isaacs, A.J. (Aaron), Ladenvall, C. (Claes), Beekman, M. (Marian), Esko, T. (Tõnu), Ried, J.S. (Janina), Nelson, C.P. (Christopher P.), Willenborg, C. (Christina), Gustafsson, S. (Stefan), Westra, H.J. (Harm-Jan), Blades, M. (Matthew), De Craen, A.J.M. (Anton J. M.), Geus, E.J.C. (Eco) de, Deelen, J. (Joris), Grallert, H. (Harald), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hengstenberg, C. (Christian), Houwing-Duistermaat, J.J. (Jeanine), Hypponen, E. (Elina), Karssen, L.C. (Lennart), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Magnusson, P.K. (Patrik), Mihailov, E. (Evelin), Müller-Nurasyid, M. (Martina), Mpindi, J.-P. (John-Patrick), Pedersen, N.L. (Nancy L.), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pers, T.H. (Tune), Peters, A. (Annette), Rung, J. (Johan), Smit, J.H. (Johannes), Steinthorsdottir, V. (Valgerdur), Tobin, M.D. (Martin), Tsernikova, N. (Natalia), Leeuwen, E.M. (Elisa) van, Viikari, J. (Jorma), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Samani, N.J. (Nilesh), Kaprio, J. (Jaakko), Lind, L. (Lars), Gieger, C. (Christian), Metspalu, A. (Andres), Slagboom, P.E. (Eline), Groop, L. (Leif), Duijn, C.M. (Cornelia) van, Eriksson, J.G. (Johan G.), Jula, A. (Antti), Salomaa, V. (Veikko), Boomsma, D.I. (Dorret), Power, C. (Christopher), Raitakari, O.T. (Olli T.), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Thorsteinsdottir, U. (Unnur), Franke, L. (Lude), Ikonen, E. (Elina), Kallioniemi, O. (Olli), Pietiäinen, V. (Vilja), Lindgren, C.M. (Cecilia M.), Zwart, J-A. (John-Anker), Palotie, A. (Aarno), McCarthy, M.I. (Mark), Morris, A.P. (Andrew), Prokopenko, I. (Inga), and Ripatti, S. (Samuli)

Abstract

Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.

Published
2015
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132. IL7R gene expression network associates with human healthy ageing

Author

Passtoors, WM, van den Akker, EB, Deelen, J, Maier, AB, van der Breggen, R, Jansen, R, Trompet, S, van Heemst, D, Derhovanessian, E, Pawelec, G, van Ommen, G-JB, Slagboom, PE, Beekman, M, Passtoors, WM, van den Akker, EB, Deelen, J, Maier, AB, van der Breggen, R, Jansen, R, Trompet, S, van Heemst, D, Derhovanessian, E, Pawelec, G, van Ommen, G-JB, Slagboom, PE, and Beekman, M

Abstract

BACKGROUND: The level of expression of the interleukin 7 receptor (IL7R) gene in blood has recently been found to be associated with familial longevity and healthy ageing. IL7R is crucial for T cell development and important for immune competence. To further investigate the IL7R pathway in ageing, we identified the closest interacting genes to construct an IL7R gene network that consisted of IL7R and six interacting genes: IL2RG, IL7, TSLP, CRLF2, JAK1 and JAK3. This network was explored for association with chronological age, familial longevity and immune-related diseases (type 2 diabetes, chronic obstructive pulmonary disease and rheumatoid arthritis) in 87 nonagenarians, 337 of their middle-aged offspring and 321 middle-aged controls from the Leiden Longevity Study (LLS). RESULTS: We observed that expression levels within the IL7R gene network were significantly different between the nonagenarians and middle-aged controls (P = 4.6 × 10(-4)), being driven by significantly lower levels of expression in the elderly of IL7, IL2RG and IL7R. After adjustment for multiple testing and white blood cell composition and in comparison with similarly aged controls, middle-aged offspring of nonagenarian siblings exhibit a lower expression level of IL7R only (P = 0.006). Higher IL7R gene expression in the combined group of middle-aged offspring and controls is associated with a higher prevalence of immune-related disease (P = 0.001). On the one hand, our results indicate that lower IL7R expression levels, as exhibited by the members of long-lived families that can be considered as 'healthy agers', are beneficial in middle age. This is augmented by the observation that higher IL7R gene expression associates with immune-related disease. On the other hand, IL7R gene expression in blood is lower in older individuals, indicating that low IL7R gene expression might associate with reduced health. Interestingly, this contradictory result is supported by the observation that a higher IL

Published
2015

133. IL7R gene expression network associates with human healthy ageing

Author

Passtoors, W.M. (author), Van den Akker, E.B. (author), Deelen, J. (author), Maier, A.B. (author), Van der Breggen, R. (author), Jansen, R. (author), Trompet, S. (author), Van Heemst, D. (author), Derhovanessian, E. (author), Pawelec, G. (author), Van Ommen, G.J.B. (author), Slagboom, P.E. (author), Beekman, M. (author), Passtoors, W.M. (author), Van den Akker, E.B. (author), Deelen, J. (author), Maier, A.B. (author), Van der Breggen, R. (author), Jansen, R. (author), Trompet, S. (author), Van Heemst, D. (author), Derhovanessian, E. (author), Pawelec, G. (author), Van Ommen, G.J.B. (author), Slagboom, P.E. (author), and Beekman, M. (author)

Abstract

Intelligent Systems, Electrical Engineering, Mathematics and Computer Science

Published
2015

134. In vivo efficacy of HD0471953:A novel GPR119 agonist for the treatment of type 2 diabetes mellitus

Author

'T Hart, L. M., Fritsche, A., Nijpels, G., Van Leeuwen, N., Donnelly, L. A., Dekker, J. M., Alssema, M., Fadista, J., Carlotti, F., Gjesing, A. P., Palmer, C. N., Van Haeften, T. W., Herzberg-Schäfer, S. A., Simonis-Bik, A. M., Houwing-Duistermaat, J. J., Helmer, Q., Deelen, J., Guigas, B., Hansen, T., MacHicao, F., Willemsen, G., Heine, R. J., Kramer, M. H., Holst, J. J., De Koning, E. J., Häring, H. U., Pedersen, O., Groop, L., De Geus, E. J., Slagboom, P. E., Boomsma, D. I., Eekhoff, E. M., Pearson, E. R., Diamant, M., 'T Hart, L. M., Fritsche, A., Nijpels, G., Van Leeuwen, N., Donnelly, L. A., Dekker, J. M., Alssema, M., Fadista, J., Carlotti, F., Gjesing, A. P., Palmer, C. N., Van Haeften, T. W., Herzberg-Schäfer, S. A., Simonis-Bik, A. M., Houwing-Duistermaat, J. J., Helmer, Q., Deelen, J., Guigas, B., Hansen, T., MacHicao, F., Willemsen, G., Heine, R. J., Kramer, M. H., Holst, J. J., De Koning, E. J., Häring, H. U., Pedersen, O., Groop, L., De Geus, E. J., Slagboom, P. E., Boomsma, D. I., Eekhoff, E. M., Pearson, E. R., and Diamant, M.

Published
2015

135. Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation

Author

Horikoshi, M, Magi, R, van de Bunt, M, Surakka, I, Sarin, AP, Mahajan, A, Marullo, L, Thorleifsson, G, Hagg, S, Hottenga, JJ (Jouke Jan), Ladenvall, C, Ried, JS, Winkler, TW, Willems, SM, Pervjakova, N, Esko, T, Beekman, M, Nelson, CP, Willenborg, C, Wiltshire, S, Ferreira, T, Fernandez, J, Gaulton, KJ, Steinthorsdottir, V, Hamsten, A, Magnusson, PKE, Willemsen, G, Milaneschi, Y, Robertson, NR, Groves, CJ, Bennett, AJ, Lehtimaki, T, Viikari, JS, Rung, J, Lyssenko, V, Perola, M, Heid, IM, Herder, Cindy, Grallert, H, Muller-Nurasyid, M, Roden, M, Hypponen, E, Isaacs, Aaron, Leeuwen, Elisa, Karssen, Lennart, Mihailov, E, Houwing-Duistermaat, JJ, de Craen, AJM, Deelen, J, Havulinna, AS, Blades, M, Hengstenberg, C, Erdmann, J, Schunkert, H, Kaprio, J, Tobin, MD, Samani, NJ, Lind, L, Salomaa, V, Lindgren, CM, Slagboom, PE (Eline), Metspalu, A, Duijn, Cornelia, Eriksson, JG, Peters, A, Gieger, C, Jula, A, Groop, L, Raitakari, OT, Power, C, Penninx, BWJH, de Geus, ED, Smit, JH, Boomsma, DI, Pedersen, NL, Ingelsson, E, Thorsteinsdottir, U, Stefansson, K, Ripatti, S, Prokopenko, I, McCarthy, MI, Morris, AP, Horikoshi, M, Magi, R, van de Bunt, M, Surakka, I, Sarin, AP, Mahajan, A, Marullo, L, Thorleifsson, G, Hagg, S, Hottenga, JJ (Jouke Jan), Ladenvall, C, Ried, JS, Winkler, TW, Willems, SM, Pervjakova, N, Esko, T, Beekman, M, Nelson, CP, Willenborg, C, Wiltshire, S, Ferreira, T, Fernandez, J, Gaulton, KJ, Steinthorsdottir, V, Hamsten, A, Magnusson, PKE, Willemsen, G, Milaneschi, Y, Robertson, NR, Groves, CJ, Bennett, AJ, Lehtimaki, T, Viikari, JS, Rung, J, Lyssenko, V, Perola, M, Heid, IM, Herder, Cindy, Grallert, H, Muller-Nurasyid, M, Roden, M, Hypponen, E, Isaacs, Aaron, Leeuwen, Elisa, Karssen, Lennart, Mihailov, E, Houwing-Duistermaat, JJ, de Craen, AJM, Deelen, J, Havulinna, AS, Blades, M, Hengstenberg, C, Erdmann, J, Schunkert, H, Kaprio, J, Tobin, MD, Samani, NJ, Lind, L, Salomaa, V, Lindgren, CM, Slagboom, PE (Eline), Metspalu, A, Duijn, Cornelia, Eriksson, JG, Peters, A, Gieger, C, Jula, A, Groop, L, Raitakari, OT, Power, C, Penninx, BWJH, de Geus, ED, Smit, JH, Boomsma, DI, Pedersen, NL, Ingelsson, E, Thorsteinsdottir, U, Stefansson, K, Ripatti, S, Prokopenko, I, McCarthy, MI, and Morris, AP

Abstract

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency >= 0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.

Published
2015

136. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

Leeuwen, Elisa, Karssen, Lennart, Deelen, J, Isaacs, Aaron, Medina-Gomez, C, Mbarek, H, Kanterakis, A, Trompet, S, Postmus, I, Verweij, N (Niek), van Enckevort, DJ, Huffman, JE, White, CC, Feitosa, MF, Bartz, TM, Manichaikul, A, Joshi, PK, Peloso, GM, Deelen, P, Dijk, Femke, Willemsen, G, de Geus, EJ, Milaneschi, Y, Penninx, BWJH, Francioli, LC, Menelaou, A, Pulit, SL, Rivadeneira, Fernando, Hofman, Bert, Oostra, Ben, Franco Duran, OH, Leach, IM, Beekman, M, de Craen, AJM, Uh, HW, Trochet, H, Hocking, LJ, Porteous, DJ, Sattar, N, Packard, CJ, Buckley, BM, Brody, JA, Bis, JC, Rotter, JI, Mychaleckyj, JC, Campbell, H, Duan, Q, Lange, LA, Wilson, JF, Hayward, C, Polasek, O, Vitart, V, Rudan, I, Wright, AF, Rich, SS, Psaty, BM, Borecki, IB, Kearney, PM, Stott, DJ, Cupples, LA, Jukema, JW, van der Harst, P, Sijbrands, E.J.G., Hottenga, JJ (Jouke Jan), Uitterlinden, André, Swertz, MA, van Ommen, GJB, de Bakker, PIW, Slagboom, PE (Eline), Boomsma, DI, Wijmenga, C, Duijn, Cornelia, Leeuwen, Elisa, Karssen, Lennart, Deelen, J, Isaacs, Aaron, Medina-Gomez, C, Mbarek, H, Kanterakis, A, Trompet, S, Postmus, I, Verweij, N (Niek), van Enckevort, DJ, Huffman, JE, White, CC, Feitosa, MF, Bartz, TM, Manichaikul, A, Joshi, PK, Peloso, GM, Deelen, P, Dijk, Femke, Willemsen, G, de Geus, EJ, Milaneschi, Y, Penninx, BWJH, Francioli, LC, Menelaou, A, Pulit, SL, Rivadeneira, Fernando, Hofman, Bert, Oostra, Ben, Franco Duran, OH, Leach, IM, Beekman, M, de Craen, AJM, Uh, HW, Trochet, H, Hocking, LJ, Porteous, DJ, Sattar, N, Packard, CJ, Buckley, BM, Brody, JA, Bis, JC, Rotter, JI, Mychaleckyj, JC, Campbell, H, Duan, Q, Lange, LA, Wilson, JF, Hayward, C, Polasek, O, Vitart, V, Rudan, I, Wright, AF, Rich, SS, Psaty, BM, Borecki, IB, Kearney, PM, Stott, DJ, Cupples, LA, Jukema, JW, van der Harst, P, Sijbrands, E.J.G., Hottenga, JJ (Jouke Jan), Uitterlinden, André, Swertz, MA, van Ommen, GJB, de Bakker, PIW, Slagboom, PE (Eline), Boomsma, DI, Wijmenga, C, and Duijn, Cornelia

Abstract

Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (similar to 35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value < 6.61 x 10(-4)), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (beta(LDL-C) = 0.135, beta(TC) = 0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.

Published
2015

137. Identification of seven loci affecting mean telomere length and their association with disease

Author

Codd V, Nelson CP, Albrecht E, Mangino M, Deelen J, Buxton JL, Hottenga JJ, Fischer K, Esko T, Surakka I, Broer L, Nyholt DR, Mateo Leach I, Salo P, Hxe4gg S, Willemsen G, Perola M, Ouwehand W, Kaprio J, Martin NG, van Duijn CM, Hovatta I, Gieger C, Metspalu A, Boomsma DI, Jarvelin MR, Slagboom PE, Thompson JR, Spector TD, van der Harst P, and Samani NJ

Published
2013

138. APCVD of ZnO: Al, insight and control by modeling

Author

Deelen, J. van, Illiberi, A., Kniknie, B.J., Steijvers, H.L.A.H., Lankhorst, A.M., Simons, P.J.P.M., and TNO, Dept. Thin Film Technology, De Rondom 1, 5612 AP Eindhoven, Netherlands Celsian Glass and Solar B.V., De Rondom 1, 5612 AP Eindhoven, Netherlands

Subjects
TS - Technical Sciences, Industrial Innovation, Industrial reactors, Transparent conductors, High Tech Systems & Materials, Mechatronics, Mechanics & Materials, CVD, TFT - Thin Film Technology, Zinc oxide, ZnO, Chemical vapor deposition, Deposition temperatures, Atmospheric pressure, Reaction intermediates, Increasing temperatures, Materials, APCVD, Surface reactions
Abstract

Atmospheric pressure chemical vapor deposition (APCVD) of ZnO from diethyl zinc (DEZn) and t-butanol was performed using an industrial reactor design. Deposition profiles were recorded to gain insight in the position dependent variations in layer thickness in such a reactor. We observed that for a deposition temperature below 400 °C most of the deposition took place close to the exit of the gasses, while for increasing temperatures the deposition shifts towards the gas inlet. This trend can be explained by the reaction mechanism through an intermediate alkoxide species from DEZn and t-butanol, which in turn leads to ZnO deposition through a surface reaction. The deposition profile is dependent on the local alkoxide concentration. With increasing temperature, the formation rate increases. This translates in an earlier formation, i.e. in a shift upstream towards gas inlet because this alkoxide formation takes place during the transport through the reactor. Chemical vapor deposition (CVD) is a highly complex system with many interacting physical and chemical processes. Modeling was used to gain insight on the local variations of the concentration of reactive species inside a reactor and was shown to predict the deposition profiles. Moreover, the impact of changes in reactor design on the deposition is discussed. © 2013 Elsevier B.V.

Published
2013

139. Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study

Author

Beekman, M., Blanche, H., Perola, M., Hervonen, A., Bezrukov, V., Sikora, E., Flachsbart, F., Christiansen, L., Craen, A.J.M. de, Kirkwood, T.B.L., Rea, I.M., Poulain, M., Robine, J.M., Valensin, S., Stazi, M.A., Passarino, G., Deiana, L., Gonos, E.S., Paternoster, L., Sorensen, T.I.A., Tan, Q.H., Helmer, Q., Akker, E.B. van den, Deelen, J., Martella, F., Cordell, H.J., Ayers, K.L., Vaupel, J.W., Tornwall, O., Johnson, T.E., Schreiber, S., Lathrop, M., Skytthe, A., Westendorp, R.G.J., Christensen, K., Gampe, J., Nebel, A., Houwing-Duistermaat, J.J., Slagboom, P.E., Franceschi, C., GEHA Consortium, Leiden University Medical Center (LUMC), Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), National Institute for Health and Welfare [Helsinki], Tampere School of Public Health, Institute of Gerontology [Kiev], Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Christian-Albrechts University of Kiel, University of Southern Denmark (SDU), Netherlands Consortium for Healthy Ageing, Newcastle University [Newcastle], The Queen’s University of Belfast, Université Catholique de Louvain = Catholic University of Louvain (UCL), CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-École des hautes études en sciences sociales (EHESS), University of Bologna, Istituto Superiore di Sanita [Rome], Università della Calabria [Arcavacata di Rende] (Unical), Università degli Studi di Sassari = University of Sassari [Sassari] (UNISS), Theoretical and Physical Chemistry Institute NHRF, National Hellenic Research Foundation, University of Bristol [Bristol], Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Odense University Hospital (OUH), Institute for Ageing and Health, Newcastle University, Max Planck Institute for Demographic Research (MPIDR), Max-Planck-Gesellschaft, University of Colorado [Boulder], Leiden University Medical Centre [Leyde, Pays-Bas], Leiden University, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institute for Ageing and Health, École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Sassari, Danish Aging Research Center, Institute of Public Health, and Institute for Behavioral Genetics

Subjects
Aging, Genetic Linkage, APOE gene, Genome-wide association study, Association analysis, Human familial longevity, [SHS]Humanities and Social Sciences, 0302 clinical medicine, Mitochondrial Precursor Protein Import Complex Proteins, Cluster Analysis, Nonagenarian sibling pairs, media_common, Aged, 80 and over, Genetics, 0303 health sciences, Longevity, Chromosome Mapping, Middle Aged, Europe, genome-wide linkage analysis, association analysis, nonagenarian sibling pairs, apoe gene, human familial longevity, congenital, hereditary, and neonatal diseases and abnormalities, media_common.quotation_subject, Locus (genetics), Biology, Article, 03 medical and health sciences, Apolipoproteins E, SDG 3 - Good Health and Well-being, Genetic linkage, Humans, Allele, Alleles, Aged, 030304 developmental biology, Genetic association, Chromosomes, Human, Pair 14, Apolipoprotein C-I, Genome, Human, Siblings, Membrane Transport Proteins, Cell Biology, Heritability, Apoe gene, Genetic Loci, Human genome, Lod Score, Chromosomes, Human, Pair 19, Genome-wide linkage analysis, 030217 neurology & neurosurgery, Chromosomes, Human, Pair 17, Genome-Wide Association Study
Abstract

Clear evidence exists for heritability of humanlongevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/ APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10 -8). By combined modeling of linkage and association, we showed that association of longevity with APOEe4 and APOEe2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10 -5, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.

Published
2013

140. Atmospheric Deposition of Zinc Oxide Front Electrode for Cu(In,Ga)Se2 and Si Thin Films Solar Cells

Author

Illiberi, A., Grob, F., Kniknie, B., Poodt, P., Van Deelen, J., Ramachandra, R., Winands, G.J.J., Simor, M., Theelen, M., Beckers, E., and Bolt, P.J.

Subjects
THIN FILM SOLAR CELLS, CdTe, CIS and Related Ternary and Quaternary Thin Film Solar Cells
Abstract

28th European Photovoltaic Solar Energy Conference and Exhibition; 2414-2417, ZnO films have been grown on a moving glass substrate by high temperature (480 0C) chemical vapour deposition (CVD) and low temperature (200 0C) plasma enhanced CVD (PE-CVD) process at atmospheric pressure. Deposition rates above 7 nm/s have been achieved for substrate speeds from 20 to 500 mm/min. The conductivity of the films is enhanced by Al doping of CVD ZnO or by exposure to near-UV radiation of PE-CVD ZnO. Both CVD ZnO:Al and UV-exposed PE-CVD i-ZnO films are highly transparent (> 85% in the visible range) and conductive (< 15 Ohm/sq for a thickness above 1200 nm). ZnO:Al has been used as front electrode in amorphous silicon (a-Si:H) solar cells while i-ZnO has been applied as electrode in CIGS solar cells, achieving an efficiency of 8% and 15.4%, respectively.

Published
2013
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141. Low Temperature Atmospheric Pressure Deposition of ZnO by Spatial-ALD and AP-PECVD

Author

Illiberi, A., Poodt, P., Grob, F., Bolt, P.J., Van Deelen, J., and Roozeboom, F.

Subjects
Thin Film Solar Cells, CdTe, CIS and Related Ternary and Quaternary Thin Film Solar Cells
Abstract

27th European Photovoltaic Solar Energy Conference and Exhibition; 2290-2293, Zinc oxide thin films have been deposited at high growth rates (up to ~ 1 nm/s) by spatial atomic layer deposition technique at atmospheric pressure. Water has been used as oxidant for diethylzinc (DEZ) at deposition temperature of 250°C. By varying the DEZ partial pressure, the electrical properties of ZnO can be controlled, ranging from heavily n-type conductive (with 4 mOhm.cm resistivity for 250 nm thickness) to insulating. All the films have c-axis (100) preferential orientation, good crystalline quality and high transparency (~ 85%) in the visible range. Combining the high deposition rates with a precise control of functional properties (i.e. conductivity and transparency) of the films, the industrially scalable spatial ALD technique can become a disruptive manufacturing method for the ZnO-based industry. Currently, we are developing a plasma enhanced chemical vapor deposition process for the growth of ZnO thin films at atmospheric pressure and low temperature (200°C).

Published
2012
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142. Low Resistive Transparent Conductors with Metallic Grids: Modeling and Experiments

Author

Van Deelen, J., Rendering, H., Het Mannetje, H., Klerk, L., and Hovestad, A.

Subjects
Material Studies, New Concepts and Ultra-High Efficiency, New Materials, Cells and Modules
Abstract

27th European Photovoltaic Solar Energy Conference and Exhibition; 322-324, At present, transparent conducting oxides (TCOs) are still superior in performance to most other transparent conductors. Results on opto-electronic modeling and design optimization of TCOs are presented using a monolithically integrated CIGS cell configuration as case. For various cell dimensions and TCO characteristics, the cell output was determined for both bare TCOs and TCOs with a metallic grid. This study showed that considerable efficiency enhancement (17% in power output) can be achieved for metal grid TCO combinations compared to single TCOs. Conductivity improvement has been experimentally verified on both commercial ITO PET foil as well as on ZnO:Al coated glass with electrochemically deposited metal grids. Conductivities below 0,1 Ohm/sq were reached and 80 times and 400 times conductivity improvements were obtained at a transparency loss of only 3% and 6%, respectively. It was also found that electrochemical deposition results in more conductive and lower surface area covering grids than obtained by Ag-ink screen printing.

Published
2012
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143. Atmospheric pressure CVD of SNO2 and ZNO:AL

Author

Van Deelen, J., Kniknie, B., Steijvers, H., Mannie, G., Thüne, P., and Illiberi, A.

Subjects
TS - Technical Sciences, Industrial Innovation, TFT - Thin Film Technology, CVD based deposition, TCO Transparent Conducting Oxides, Thin Film Solar Cells, ZnO, CdTe, CIS and Related Ternary and Quaternary Thin Film Solar Cells, High Tech Systems & Materials, Mechatronics, Mechanics & Materials, Electronics, Thin film solar cell
Abstract

27th European Photovoltaic Solar Energy Conference and Exhibition; 2286-2289, Atmospheric pressure CVD (APCVD) is a highly cost effective method of depositing transparent conductive oxides (TCOs). In this work, insights in alcohol addition in the widely applied SnO2 process are discussed, including high resolution TEM images. Furthermore, the APCVD process of ZnO:Al was demonstrated on an industrial moving belt APCVD system. A high deposition rate of 14 nm/s, a resistivity down to 0.5 mOhm cm and a transparency about 85% in the visible range were obtained. Furthermore, modeling of the CVD process clearly enhanced understanding of the process and is a good tool for process optimization in combination with experimental verification. A-Si solar cells approaching 8% were obtained, using the ZnO on glass as a superstrate.

Published
2012

144. Atmospheric pressure deposition of SnO2 and ZnO

Author

Deelen, J. van, Kniknie, B.J., Grob, F.T.J., Volintiru, I., Roozeboom, F., Poodt, P.W.G., and Illiberi, A.

Subjects
tinoxide, TS - Technical Sciences, Industrial Innovation, TFT - Thin Film Technology, transparent conductive oxides, zincoxide, High Tech Systems & Materials, Mechatronics, Mechanics & Materials, CVD, Materials, transparent conductors
Abstract

Transparent conductive oxide (TCO) coated glass is widely used in thin film PV. Atmospheric pressure chemical vapor deposition (APCVD) is a highly cost effective method of deposition and apart from metal precursor and oxygen precursor, other additives can improve the layer quality. In this contribution, we present an overview of the latest results on SnO 2 and ZnO work. First, the beneficial effect of methanol addition is discussed. By adding methanol during the SnO 2 deposition, the conductivity increased up to ten times, with remarkably high mobility values of up to 55 cm 2/Vs. The films are already very conductive at a thickness below 10 nm. This is highly beneficial to applications with strict requirements in terms of film transparency. For ZnO:Al the APCVD process was developed with a deposition rate of 14 nm/s for one injector and resistivity values down to 0.6 mΩ cm. Low temperature APCVD ZnO was achieved by introducing remote plasma in the system. Deposition rate of 7 nm/s and resistivities of 2 mΩ cm were obtained. For spatial ALD, growth rates of ZnO were up to 1 nm/s and resistivities were of the order of 4 mΩ cm. © 2012 IEEE.

Published
2012

146. Low resistive trasparent conductors with metallic grids : modeling and experiments

Author

Deelen, J. van, Rendering, H., Mannetje, H.H 't, Klerk, L., and Hovestad, A.

Subjects
TS - Technical Sciences, Industrial Innovation, Electrodeposition, TFT - Thin Film Technology, TCO Transparent Conducting Oxides, Optical losses, High Tech Systems & Materials, Mechatronics, Mechanics & Materials, Electronics, Thin film solar cell
Abstract

At present, transparent conducting oxides (TCOs) are still superior in performance to most other transparent conductors. Results on opto-electronic modeling and design optimization of TCOs are presented using a monolithically integrated CIGS cell configuration as case. For various cell dimensions and TCO characteristics, the cell output was determined for both bare TCOs and TCOs with a metallic grid. This study showed that considerable efficiency enhancement (17% increase in power output) can be achieved for metal grid TCO combinations compared to single layer TCOs. Conductivity improvement has been experimentally verified on both commercial ITO PET foil as well as on ZnO:Al coated glass with electrochemically deposited metal grids. Conductivities below 0,1 Ω/sq were reached and 80 times and 400 times conductivity improvements were obtained at a transparency loss of only 3% and 6%, respectively.

Published
2012

147. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited

Author

Deelen, J., Beekman, M., Uh, H.W., Helmer, Q., Kuningas, M., Christiansen, L., Kremer, D., Breggen, R. van der, Suchiman, H.E.D., Lakenberg, N., Akker, E.B. van den, Passtoors, W.M., Tiemeier, H., Heemst, D. van, Craen, A.J. de, Rivadeneira, F., Geus, E.J. de, Perola, M., Ouderaa, F.J. van der, Gunn, D.A., Boomsma, D.I., Uitterlinden, A.G., Christensen, K., Duijn, C.M. van, Heijmans, B.T., Houwing-Duistermaat, J.J., Westendorp, R.G.J., and Slagboom, P.E.

Subjects
aging apolipoprotein E genetics genome-wide association study human longevity apolipoprotein-e genotype growth-factor-i human longevity leiden longevity familial longevity alzheimers-disease nonagenarian siblings exceptional longevity depressive disorder artery-disease
Abstract

By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Study (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study, and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P < 1 x 10(-4)) showed genome-wide significance with survival into old age in the meta-analysis of 4149 nonagenarian cases and 7582 younger controls [OR = 0.71 (95% CI 0.65-0.77), P = 3.39 x 10(-17)]. This SNP, rs2075650, is located in TOMM40 at chromosome 19q13.32 close to the apolipoprotein E (APOE) gene. Although there was only moderate linkage disequilibrium between rs2075650 and the ApoE epsilon 4 defining SNP rs429358, we could not find an APOE-independent effect of rs2075650 on longevity, either in cross-sectional or in longitudinal analyses. As expected, rs429358 associated with metabolic phenotypes in the offspring of the nonagenarian cases from the LLS and their partners. In addition, we observed a novel association between this locus and serum levels of IGF-1 in women (P = 0.005). In conclusion, the major locus determining familial longevity up to high age as detected by GWAS was marked by rs2075650, which tags the deleterious effects of the ApoE epsilon 4 allele. No other major longevity locus was found.

Published
2011

148. Grids on TCO's for higly transparent materials with a resistivity below 1 Ohm/sq

Author

Deelen, J. van, Rendering, H., Mannetje, H.H 't, and Hovestad, A.

Subjects
TS - Technical Sciences, Industrial Innovation, TFT - Thin Film Technology, Mechatronics, Mechanics & Materials, Materials
Abstract

Various transparent conducting materials are compared based on their transparency versus sheet resistance characteristics. At present, transparent conducting oxides (TCOs) are still superior in performance compared to various recent alternatives and can only be surpassed by the combination of TCOs with a metal grid. Results on modeling and design optimization are presented using a monolithically integrated CIGS cell configuration as case. This study showed that considerable efficiency enhancement (17% in power output) can be achieved for metal grid TCO combinations compared to single TCOs. Conductivity improvement has been experimentally verified on both commercial ITO PET foil as well as on ZnO coated glass with electrochemically deposited metal grids. Conductivities below 0,1 Ohm/sq were reached and 80 times and 400 times conductivity improvements were obtained at a transparency loss of only 3% and 6%, respectively. It was also found that electrochemical deposition results in more conductive and more transparent grids than obtained by Ag-ink screen printing. © 2011 IEEE.

Published
2011

149. Review of Transparent Conductors and Demonstrated Improvement Strategy Using Metallic Grids

Author

Van Deelen, J., Rendering, H., Klerk, L., Poodt, P., and Hovestad, A.

Subjects
CIS and Related Ternary and Quaternary Thin Film Solar Cells, Thin Film Solar Cells
Abstract

26th European Photovoltaic Solar Energy Conference and Exhibition; 2998-3000, A comparison of various transparent conducting materials based on their transparency versus sheet resistance characteristics is presented. Transparent conducting oxides (TCOs) are still superior in performance compared to various recent alternatives and can only be surpassed by the combination of TCOs with a metal grid. Results on modeling and design optimization are presented using a monolithically integrated CIGS cell configuration as case. This study showed that considerable efficiency enhancement (17% in power output) can be achieved for metal grid TCO combinations compared to single TCOs. Conductivity improvement has been experimentally verified on both commercial ITO PET foil as well as on ZnO coated glass with electrochemically deposited metal grids. Conductivities below 0,1 Ohm/sq were reached and 80 times and 400 times conductivity improvements were obtained at a transparency loss of only 3% and 6%, respectively. It was also found that electrochemical deposition results in more conductive and more transparent grids than obtained by Ag-ink screen printing.

Published
2011
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150. Transmission electron microscopy of transparent conductive oxide films made by atmospheric pressure chemical vapor deposition

Author

Mannie, G.J.A., Deelen, J. van, Niemantsverdriet, J.W., and Thüne, P.C.

Subjects
TS - Technical Sciences, Industrial Innovation, TFT - Thin Film Technology, Physics, High Tech Systems & Materials, Mechatronics, Mechanics & Materials
Abstract

The properties of crystalline films are strongly dependent on the morphology development during the first stages of growth, that is, the nucleation and growth of the first crystallites. The ideal method to investigate such films at atomic resolution is transmission electron microscopy (TEM). However, this technique usually requires extensive sample preparation. In this study we present a simple method to investigate thin film morphology with TEM. The key to this approach is the use of TEM membranes as growth substrates. As an illustration we describe fine grains of SnO2 deposited on these TEM membranes by atmospheric pressure chemical vapor deposition. © 2011 American Institute of Physics.

Published
2011

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