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179 results on '"Pichler, S."'

1. The impact of the international code of marketing of breast-milk substitutes in Ghana and Tanzania

Author: Lima Constantino, J, primary, Biesma, R, additional, Pichler, S, additional, and Kramer, L, additional
Published: 2023
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2. Higher-derivative gravity in brane world models

Author: Parry, M., Pichler, S., and Deeg, D.
Subjects: High Energy Physics - Phenomenology, General Relativity and Quantum Cosmology, High Energy Physics - Theory
Abstract: We investigate brane world models in higher-derivative gravity theories where the gravitational Lagrangian is an arbitrary function of the Ricci scalar. Making use of the conformal equivalence of such gravity models and Einstein-Hilbert gravity with a scalar field, we deduce the main features of higher-derivative gravity brane worlds. We solve for a gravity model that has corrections quadratic in the Ricci scalar and show one can evade both fine-tuning and the need for a bulk cosmological constant. An analysis of tensor and scalar perturbations shows gravity is localized on the brane and we recover the Newtonian limit., Comment: 11 pages, 4 figures
Published: 2005
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3. New bulk scalar field solutions in brane worlds

Author: Parry, M. and Pichler, S.
Subjects: High Energy Physics - Phenomenology, Astrophysics
Abstract: We use nonlinear perturbation theory to obtain new solutions for brane world models that incorporate a massive bulk scalar field. We then consider tensor perturbations and show that Newtonian gravity is recovered on the brane for both a light scalar field and for a bulk field with large negative mass. This latter result points to the viability of higher-derivative theories of gravity in the context of bulk extra dimensions., Comment: 4+\epsilon pages, no figures
Published: 2004
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4. Missing Lactase Persistence in Late Iron Age Central Europe

Author: Warnberg, O., Knipper, C., Röder, B., Lassau, G., Spichtig, N., Ramsl, P., Novotny, F., Teschler-Nicola, M., Marion, S., Schönfelder, M., Pare, C., Szécsényi-Nagy, A., Schibler, J., Schiffels, S., https://orcid.org/0000-0002-1017-9150, Alt, K., and Pichler, S.
Abstract: Missing Lactase Persistence in Late Iron Age Central Europe Being able to digest milk sugar beyond the age of weaning is a rather new trait in humans. The calculated age of the responsible mutations largely coincides with the introduction of dairy farming. Recent European populations exhibit a gradient of high levels of lactose tolerance in the north and lower numbers in the south. Lactase persistence is believed to have co-evolved with farming or livestock keeping as a selective advantage. Palaeogenetic data of prehistoric individuals, however, have so far not provided any clear evidence that the spread of the lactase persistence mutation predates the Roman period, while persistence increases throughout the Middle Ages. In contrast, evidence of dairy processing reaches back to the introduction of farming in the Neolithic. In this paper, we investigate lactase persistence in the La Tène period of the European Iron Age. 39 individuals from Austria, France, Hungary and Switzerland have been successfully genotyped for the two single nucleotide polymorphisms (SNPs) 13910C/T and 22018G/A, which are associated with lactose tolerance. None of those individuals carries the homozygous variant of either of the two SNPs, while four individuals are heterozygous at 22018G/A. This implies that during the Iron Age processed dairy products like cheese and yoghurt still represented the common supply of milk-derived nutrients while fresh milk played only a minor role in the regions studied here. The population-wide spread of the lactose tolerance trait in Europe therefore clearly post-dates the Iron Age., Archäologisches Korrespondenzblatt, Bd. 52 Nr. 2 (2022): Archäologisches Korrespondenzblatt
Published: 2023
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5. Protein network analysis reveals selectively vulnerable regions and biological processes in FTD

Author: Bonham, Luke W., Steele, Natasha Z.R., Karch, Celeste M., Manzoni, Claudia, Geier, Ethan G., Wen, Natalie, Ofori-Kuragu, Aaron, Momeni, Parastoo, Hardy, John, Miller, Zachary A., Hess, Christopher P., Lewis, Patrick, Miller, Bruce L., Seeley, William W., Baranzini, Sergio E., Desikan, Rahul S., Ferrari, Raffaele, Yokoyama, Jennifer S., Ferrari, R, Hernandez, D G, Nalls, M A, Rohrer, J D, Ramasamy, A, Kwok, J B J, Dobson-Stone, C, Schofield, P R, Halliday, G M, Hodges, J R, Piguet, O, Bartley, L, Thompson, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, N J, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, M Landqvist, Nilsson, K, Nilsson, C, Mackenzie, I R A, Hsiung, G-Y R, Mann, D, Grafman, J, Morris, C M, Attems, J, Griffiths, T D, McKeith, I G, Thomas, A J, Pietrini, P, Huey, E D, Wassermann, E M, Baborie, A, Jaros, E, Tierney, M C, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Albani, D., Rowe, J B, Schlachetzki, J C M, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, V M, Grossman, M, Trojanowski, J Q, van der Zee, J, Van Broeckhoven, C, Cappa, S F, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, J E, Hjermind, L E, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, M N, Fox, N C, Warren, J D, Spillantini, M G, Morris, H R, Rizzu, P, Heutink, P, Snowden, J S, Rollinson, S, Richardson, A, Gerhard, A, Bruni, A C, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, M E, Smirne, N, Rademakers, R, Baker, M, Dickson, D W, Graff-Radford, N R, Petersen, R C, Knopman, D, Josephs, K A, Boeve, B F, Parisi, J E, Seeley, W W, Miller, B L, Karydas, A M, Rosen, H, van Swieten, J C, Dopper, E G P, Seelaar, H, Pijnenburg, Y A L, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, A A, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, H-H, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, A B, Hardy, J, and Momeni, P
Published: 2018
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6. Family-supportive supervisor behaviors (FSSB) and work-family conflict: The role of stereotype content, supervisor gender, and gender role beliefs

Author: Yu, A, Pichler, S, Russo, M, Hammer, L, Yu, A, Pichler, S, Russo, M, and Hammer, L
Abstract: Existing research consistently shows that informal workplace support, such as family‐supportive supervisor behaviors (FSSB), are more effective at reducing work–family conflict than formal organizational supports. The purpose of this study is to integrate propositions from the stereotype content model and social role theory to understand how family‐supportive supervision is related to social evaluations of supervisors (i.e., perceptions of supervisor warmth and competence) and identify boundary conditions (i.e., supervisor gender and employee gender role beliefs) to help researchers and practitioners understand how these relationships affect work–family conflict. We test our hypotheses using two studies, one an experimental vignette study and the other a two‐wave survey study of working individuals with family or caregiving responsibilities. Our results suggest that FSSB are importantly related to how employees socially evaluate their supervisors along the dimensions of warmth and competence; supervisor gender moderates the relationship between FSSB and perceived competence (but not warmth); employee gender role beliefs moderates both these relationship (but in a counterintuitive way for supervisor competence); and we find evidence that warmth and competence mediate the effects that FSSB have on work–family conflict. Implications for theory, future research, and practice are discussed. Practitioner points Supervisors and organizations should consider how employee perceptions of supervisor competence and warmth impact employee perceptions of family supportiveness. When enacting family supportive behavior, it is important for supervisors to demonstrate warmth, such as through nonverbal communication and body language. Family‐supportive supervisor behavior (FSSB) interventions should consider manipulating not only dimensions of FSSB, but also behaviors tied to perceptions of competence and warmth.
Published: 2022

7. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimerʼs and Parkinsonʼs diseases

Author: Ferrari, Raffaele, Wang, Yunpeng, Vandrovcova, Jana, Guelfi, Sebastian, Witeolar, Aree, Karch, Celeste M, Schork, Andrew J, Fan, Chun C, Brewer, James B, Momeni, Parastoo, Schellenberg, Gerard D, Dillon, William P, Sugrue, Leo P, Hess, Christopher P, Yokoyama, Jennifer S, Bonham, Luke W, Rabinovici, Gil D, Miller, Bruce L, Andreassen, Ole A, Dale, Anders M, Hardy, John, Desikan, Rahul S, Hernandez, D G, Nalls, M A, Rohrer, J D, Ramasamy, A, Kwok, J B J, Dobson-Stone, C, Schofield, P R, Halliday, G M, Hodges, J R, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, N J, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Landqvist Waldö, M, Nilsson, K, Nilsson, C, Mackenzie, I R A, Hsiung, G-Y R, Mann, D M A, Grafman, J, Morris, C M, Attems, J, Griffiths, T D, McKeith, I G, Thomas, A J, Pietrini, P, Huey, E D, Wassermann, E M, Baborie, A, Jaros, E, Tierney, M C, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, J B, Schlachetzki, J C M, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, V M, Grossman, M, Trojanowski, J Q, van der Zee, J, Cruts, M, Van Broeckhoven, C, Cappa, S F, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, J E, Hjermind, L E, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, M N, Fox, N C, Warren, J D, Spillantini, M G, Morris, H R, Rizzu, P, Heutink, P, Snowden, J S, Rollinson, S, Richardson, A, Gerhard, A, Bruni, A C, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, M E, Smirne, N, Rademakers, R, Baker, M, Dickson, D W, Graff-Radford, N R, Petersen, R C, Knopman, D, Josephs, K A, Boeve, B F, Parisi, J E, Seeley, W W, Karydas, A M, Rosen, H, van Swieten, J C, Dopper, E G P, Seelaar, H, Pijnenburg, Y A L, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, A A, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, H-H, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, and Singleton, A B
Published: 2017
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8. Plasmon-enhanced fluorescence in heterochlorophyllous peridinin-chlorophyll-protein photosynthetic complex

Author: Krajnik, B., Czechowski, N., Ciszak, K., Piatkowski, D., Mackowski, S., Brotosudarmo, T.H.P., Scheer, H., Pichler, S., and Heiss, W.
Published: 2012
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9. Growth and characterization of mid-infrared microdisk lasers operating in continuous-wave mode up to 2 °C

Author: Eibelhuber, M., Schwarzl, T., Pichler, S., Heiss, W., and Springholz, G.
Published: 2011
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10. A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers

Author: Zhang M1, 2 3, Ferrari R4, Tartaglia MC3, 5 6, Keith J7, Surace EI8, Wolf U9, Sato C3, Grinberg M3, Liang Y3, Xi Z3, Dupont K3, McGoldrick P3, Weichert A3, McKeever PM3, Schneider R3, 6 7, McCorkindale MD4, Manzoni C10, Rademakers R11, Graff-Radford NR12, Dickson DW11, Parisi JE13, Boeve BF14, Petersen RC14, Miller BL15, Seeley WW16, van Swieten JC17, van Rooij J17, Pijnenburg Y18, van der Zee J19, Van Broeckhoven C19, Le Ber I21, Van Deerlin V23, Suh E23, Rohrer JD24, Mead S25, Graff C26, Öijerstedt L26, Pickering-Brown S28, Rollinson S28, Rossi G29, Tagliavini F30, Brooks WS31, Dobson-Stone C32, Halliday GM32, Hodges JR32, Piguet O34, Binetti G36, Benussi L37, Ghidoni R37, Nacmias B38, Sorbi S38, Bruni AC40, Galimberti D41, Scarpini E41, Rainero I42, Rubino E42, Clarimon J43, Lleó A43, Ruiz A45, Hernández I45, Pastor P46, Diez-Fairen M46, Borroni B48, Pasquier F49, Deramecourt V49, Lebouvier T49, Perneczky R50, 51 52, Diehl-Schmid J50, Grafman J53, Huey ED55, Mayeux R55, Nalls MA57, Hernandez D57, Singleton A57, Momeni P58, Zeng Z59, Hardy J4, Robertson J3, Zinman L6, 7, Rogaeva E3, 6, International FTD-Genomics Consortium (IFGC), Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JBJ, Dobson-Stone C, Brooks WS, Schofield PR, Halliday GM, Hodges JR, Piguet O, Bartley L, Thompson E, Hernández I, Ruiz A, Boada M, Borroni B, Padovani A, Cruchaga C, Cairns NJ, Benussi L, Binetti G, Ghidoni R, Forloni G, Albani D, Galimberti D, Fenoglio C, Serpente M, Scarpini E, Clarimón J, Lleó A, Blesa R, Wald Ouml ML, Nilsson K, Nilsson C, Mackenzie IRA, Hsiung GR, Mann DMA, Grafman J, Morris CM, Attems J, Griffiths TD, McKeith IG, Thomas AJ, Pietrini P, Huey ED, Wassermann EM, Baborie A, Jaros E, Tierney MC, Pastor P, Razquin C, Ortega-Cubero S, Alonso E, Perneczky R, Diehl-Schmid J, Alexopoulos P, Kurz A, Rainero I, Rubino E, Pinessi L, Rogaeva E, St George-Hyslop P, Rossi G, Tagliavini F, Giaccone G, Rowe JB, Schlachetzki JCM, Uphill J, Collinge J, Mead S, Danek A, Van Deerlin VM, Grossman M, Trojanowski JQ, van der Zee J, Van Broeckhoven C, Cappa SF, Leber I, Hannequin D, Golfier V, Vercelletto M, Brice A, Nacmias B, Sorbi S, Bagnoli S, Piaceri I, Nielsen JE, Hjermind LE, Riemenschneider M, Mayhaus M, Ibach B, Gasparoni G, Pichler S, Gu W, Rossor MN, Fox NC, Warren JD, Grazia Spillantini M, Morris HR, Rizzu P, Heutink P, Snowden JS, Rollinson S, Richardson A, Gerhard A, Bruni AC, Maletta R, Frangipane F, Cupidi C, Bernardi L, Anfossi M, Gallo M, Elena Conidi M, Smirne N, Rademakers R, Baker M, Dickson DW, Graff-Radford NR, Petersen RC, Knopman D, Josephs KA, Boeve BF, Parisi JE, Seeley WW, Miller BL, Karydas AM, Rosen H, van Swieten JC, Dopper EGP, Seelaar H, Pijnenburg YAL, Scheltens P, Logroscino G, Capozzo R, Novelli V, Puca AA, Franceschi M, Postiglione A, Milan G, Sorrentino P, Kristiansen M, Chiang HH, Graff C, Pasquier F, Rollin A, Deramecourt V, Lebouvier T, Kapogiannis D, Ferrucci L, Pickering-Brown S, Singleton AB, Hardy J, Momeni P, Human genetics, Amsterdam Neuroscience - Neurodegeneration, Neurology, Divisions, Zhang, M1, 2, 3, Ferrari, R4, Tartaglia, Mc3, 5, 6, Keith, J7, Surace, Ei8, Wolf, U9, Sato, C3, Grinberg, M3, Liang, Y3, Xi, Z3, Dupont, K3, Mcgoldrick, P3, Weichert, A3, Mckeever, Pm3, Schneider, R3, 6, 7, Mccorkindale, Md4, Manzoni, C10, Rademakers, R11, Graff-Radford, Nr12, Dickson, Dw11, Parisi, Je13, Boeve, Bf14, Petersen, Rc14, Miller, Bl15, Seeley, Ww16, van Swieten, Jc17, van Rooij, J17, Pijnenburg, Y18, van der Zee, J19, Van Broeckhoven, C19, Le Ber, I21, Van Deerlin, V23, Suh, E23, Rohrer, Jd24, Mead, S25, Graff, C26, Öijerstedt, L26, Pickering-Brown, S28, Rollinson, S28, Rossi, G29, Tagliavini, F30, Brooks, Ws31, Dobson-Stone, C32, Halliday, Gm32, Hodges, Jr32, Piguet, O34, Binetti, G36, Benussi, L37, Ghidoni, R37, Nacmias, B38, Sorbi, S38, Bruni, Ac40, Galimberti, D41, Scarpini, E41, Rainero, I42, Rubino, E42, Clarimon, J43, Lleó, A43, Ruiz, A45, Hernández, I45, Pastor, P46, Diez-Fairen, M46, Borroni, B48, Pasquier, F49, Deramecourt, V49, Lebouvier, T49, Perneczky, R50, 51, 52, Diehl-Schmid, J50, Grafman, J53, Huey, Ed55, Mayeux, R55, Nalls, Ma57, Hernandez, D57, Singleton, A57, Momeni, P58, Zeng, Z59, Hardy, J4, Robertson, J3, Zinman, L6, Rogaeva, E3, International FTD-Genomics Consortium, (IFGC), Ferrari, R, Hernandez, Dg, Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jbj, Dobson-Stone, C, Brooks, W, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Wald Ouml, Ml, Nilsson, K, Nilsson, C, Mackenzie, Ira, Hsiung, Gr, Mann, Dma, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wassermann, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jcm, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, Vm, Grossman, M, Trojanowski, Jq, van der Zee, J, Van Broeckhoven, C, Cappa, Sf, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Grazia Spillantini, M, Morris, Hr, Rizzu, P, Heutink, P, Snowden, J, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Elena Conidi, M, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff-Radford, Nr, Petersen, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Miller, Bl, Karydas, Am, Rosen, H, van Swieten, Jc, Dopper, Egp, Seelaar, H, Pijnenburg, Yal, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, Ab, Hardy, J, Momeni, P, and Int FTD-Genomics Consortium IFGC
Subjects: Male, Heterozygote, amyotrophic lateral sclerosis, Genotype, genetic association, Age of onset, Polymorphism, Single Nucleotide, frontotemporal dementia, age of onset, C9orf72, Humans, amyotrophic lateral sclerosi, Aged, C9orf72 Protein, Original Articles, DNA Methylation, Middle Aged, Amyotrophic lateral sclerosis, Gene Expression Regulation, Genetic association, CpG Islands, Female, Human medicine, Neurology (clinical), Frontotemporal dementia
Abstract: Discovery of disease age-of-onset modifiers is important for clinical trials and drug design. Zhang et al. perform a genome-wide analysis of epigenetic functional polymorphisms and identify an association between the C6orf10/LOC101929163 locus and age of FTD/ALS onset. The risk allele may be associated with a pro-inflammatory state in the brain., The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.
Published: 2018

11. Analysis of the Performance of the Eight Superconducting Quadrupoles for the Lep Low-Beta Insertions

Author: Ferry, P. J., Semal, D., Lebrun, Ph., Pagano, O., Pichler, S., Taylor, T. M., Tortschanoff, T., Walckiers, L., Williams, L., Sekiguchi, T., editor, and Shimamoto, S., editor
Published: 1990
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12. Correction to:A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity (Acta Neuropathologica, (2019), 138, 2, (237-250), 10.1007/s00401-019-02026-8)

Author: van der Lee, Sven J., Conway, Olivia J., Jansen, Iris, Carrasquillo, Minerva M., Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R., Stringa, Najada, Chen, Jason A., Zettergren, Anna, Andlauer, Till F.M., Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E., Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J., Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A., Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M., Indakoetxea, Begoña, Collij, Lyduine E., Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W., van Berckel, Bart N.M., Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L., Pastor, Pau, Rodríguez Rodríguez, Eloy, Mead, S., Synofzik, M., van Swieten, J. C., Leber, I., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B.J., Dobson-Stone, C., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Blesa, R., Landqvist Waldö, M., Nilsson, K., Nilsson, C., Mackenzie, I. R.A., Hsiung, G. Y.R., Mann, D. M.A., Grafman, J., Morris, C. M., Attems, J., Griffiths, T. D., McKeith, I. G., Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C.M., Uphill, J., Collinge, J., Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., van der Zee, J., Van Broeckhoven, C., Cappa, S. F., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Baker, M., Josephs, K. A., Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., Dopper, E. G.P., Seelaar, H., Logroscino, G., Capozzo, R., Novelli, V., Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H. H., Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A. B., Hardy, J., Momeni, P., Boeve, Bradley F., Petersen, Ronald C., Ferman, Tanis J., van Gerpen, Jay A., Reinders, Marcel J.T., Uitti, Ryan J., Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K., van Schoor, Natasja M., Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K., Ross, Owen A., Dickson, Dennis W., Graff-Radford, Neill R., Knopman, David, Rademakers, Rosa, Lemstra, Afina W., Pijnenburg, Yolande A.L., Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F., Hemmer, Bernhard, Huisman, Martijn A., Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A., Sørensen, Thorkild I.A., Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, Coppola, G., Varpetian, A., Foroud, T. M., Levey, A. I., Kukull, W. A., Mendez, M. F., Ringman, J., Chui, H., Cotman, C., DeCarli, C., Geschwind, D. H., Clarimón, Jordi, Christensen, Kaare, Ertekin-Taner, Nilüfer, Scholz, Sonja W., Ramirez, Alfredo, Ruiz, Agustín, Slagboom, Eline, van der Flier, Wiesje M., and Holstege, Henne
Abstract: The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.
Published: 2020

13. Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity (Acta Neuropathologica, (2019), 138, 2, (237-250), 10.1007/s00401-019-02026-8)

Author: van der Lee, S. J., Conway, O. J., Jansen, I., Carrasquillo, M. M., Kleineidam, L., van den Akker, E., Hernandez, I., van Eijk, K. R., Stringa, N., Chen, J. A., Zettergren, A., Andlauer, T. F. M., Diez-Fairen, M., Simon-Sanchez, J., Lleo, A., Zetterberg, H., Nygaard, M., Blauwendraat, C., Savage, J. E., Mengel-From, J., Moreno-Grau, S., Wagner, M., Fortea, J., Keogh, M. J., Blennow, K., Skoog, I., Friese, M. A., Pletnikova, O., Zulaica, M., Lage, C., de Rojas, I., Riedel-Heller, S., Illan-Gala, I., Wei, W., Jeune, B., Orellana, A., Then Bergh, F., Wang, X., Hulsman, M., Beker, N., Tesi, N., Morris, C. M., Indakoetxea, B., Collij, L. E., Scherer, M., Morenas-Rodriguez, E., Ironside, J. W., van Berckel, B. N. M., Alcolea, D., Wiendl, H., Strickland, S. L., Pastor, P., Rodriguez Rodriguez, E., Mead, S., Synofzik, M., van Swieten, J. C., Leber, I., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Blesa, R., Landqvist Waldo, M., Nilsson, K., Nilsson, C., Mackenzie, I. R. A., Hsiung, G. -Y. R., Mann, D. M. A., Grafman, J., Attems, J., Griffiths, T. D., Mckeith, I. G., Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C. M., Uphill, J., Collinge, J., Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., van der Zee, J., Van Broeckhoven, C., Cappa, S. F., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Baker, M., Josephs, K. A., Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., Dopper, E. G. P., Seelaar, H., Logroscino, G., Capozzo, R., Novelli, V., Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H. -H., Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A. B., Hardy, J., Momeni, P., Boeve, B. F., Petersen, R. C., Ferman, T. J., van Gerpen, J. A., Reinders, M. J. T., Uitti, R. J., Tarraga, L., Maier, W., Dols-Icardo, O., Kawalia, A., Dalmasso, M. C., Boada, M., Zettl, U. K., van Schoor, N. M., Beekman, M., Allen, M., Masliah, E., de Munain, A. L., Pantelyat, A., Wszolek, Z. K., Ross, O. A., Dickson, D. W., Graff-Radford, N. R., Knopman, D., Rademakers, R., Lemstra, A. W., Pijnenburg, Y. A. L., Scheltens, P., Gasser, T., Chinnery, P. F., Hemmer, B., Huisman, M. A., Troncoso, J., Moreno, F., Nohr, E. A., Sorensen, T. I. A., Heutink, P., Sanchez-Juan, P., Posthuma, D., Coppola, G., Varpetian, A., Foroud, T. M., Levey, A. I., Kukull, W. A., Mendez, M. F., Ringman, J., Chui, H., Cotman, C., Decarli, C., Geschwind, D. H., Clarimon, J., Christensen, K., Ertekin-Taner, N., Scholz, S. W., Ramirez, A., Ruiz, A., Slagboom, E., van der Flier, W. M., Holstege, H., Neurology, Epidemiology and Data Science, Human genetics, APH - Societal Participation & Health, APH - Aging & Later Life, Amsterdam Neuroscience - Complex Trait Genetics, APH - Personalized Medicine, and APH - Methodology
Subjects: education
Abstract: The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.
Published: 2020

14. Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

Author: van der Lee, Sven J, Conway, Olivia J, Zettergren, Anna, Christensen, Kaare, Ertekin-Taner, Nilüfer, Scholz, Sonja W, Ramirez, Alfredo, Ruiz, Agustín, Slagboom, Eline, van der Flier, Wiesje M, Holstege, Henne, Mead, S., Synofzik, M., Andlauer, Till F M, van Swieten, J. C., Leber, I., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Schofield, P. R., Diez-Fairen, Monica, Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Simon-Sanchez, Javier, Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Blesa, R., Landqvist Waldö, M., Lleó, Alberto, Nilsson, K., Nilsson, C., Mackenzie, I. R. A., Hsiung, G-Y R, Mann, D. M. A., Grafman, J., Morris, C. M., Attems, J., Griffiths, T. D., McKeith, I. G., Zetterberg, Henrik, Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Razquin, C., Ortega-Cubero, S., Alonso, E., Nygaard, Marianne, Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Blauwendraat, Cornelis, Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C. M., Uphill, J., Collinge, J., Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., Savage, Jeanne E, van der Zee, J., Van Broeckhoven, C., Cappa, S. F., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Mengel-From, Jonas, Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Jansen, Iris, Moreno-Grau, Sonia, Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Wagner, Michael, Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Baker, M., Josephs, K. A., Fortea, Juan, Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., Dopper, E. G. P., Seelaar, H., Logroscino, G., Capozzo, R., Novelli, V., Keogh, Michael J, Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H-H, Graff, C., Pasquier, F., Rollin, A., Blennow, Kaj, Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A. B., Hardy, J., Momeni, P., Coppola, G., Skoog, Ingmar, Varpetian, A., Foroud, T. M., Levey, A. I., Kukull, W. A., Mendez, M. F., Ringman, J., Chui, H., Cotman, C., DeCarli, C., Friese, Manuel A, Geschwind, D. H., Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, Carrasquillo, Minerva M, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Kleineidam, Luca, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart N M, Alcolea, Daniel, Wiendl, Heinz, van den Akker, Erik, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, DESGESCO, EADB, IFGC, IPDGC, RiMod-FTD, Bank, Netherlands Brain, Boeve, Bradley F, Hernández, Isabel, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel J T, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, van Eijk, Kristel R, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Stringa, Najada, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande A L, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Chen, Jason A, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild I A, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, GIFT, and Clarimón, Jordi
Subjects: 0301 basic medicine, Dementia with Lewy bodies, Disease, Bioinformatics, Neurodegenerative disease, 0302 clinical medicine, Missense mutation, media_common, 2. Zero hunger, Longevity, Brain, Parkinson Disease, Phospholipase C Gamma 2, Biobank, 3. Good health, ddc, Frontotemporal Dementia, Microglia, Alzheimer's disease, Alzheimer’s disease, Amyotrophic lateral sclerosis, Frontotemporal dementia, Multiple sclerosis, PLCG2, Parkinson’s disease, Progressive supranuclear palsy, Lewy Body Disease, Risk, Multiple Sclerosis, media_common.quotation_subject, education, Neuroimaging, Genomics, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Alzheimer Disease, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Alleles, Phospholipase C gamma, business.industry, Amyotrophic Lateral Sclerosis, Correction, medicine.disease, 030104 developmental biology, Mutation, Dementia, Neurology (clinical), business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target. The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.
Published: 2019

15. Polygenic risk and hazard scores for Alzheimer's disease prediction

Author: Leonenko, G, Sims, R, Shoai, M, Frizzati, A, Bossù, P, Spalletta, G, Fox, Nc, Williams, J, for the GERAD consortium: Hardy, J, Escott-Price, V, Tsolaki, M, Craig, D, Avramidou, D, Germanou, A, Koutroumani, M, Gkatzima, O, Hampel, H, Kehoe, Pg, Love, S, Rubinsztein, Dc, Frölich, L, Mcguinness, B, Johnston, Ja, Passmore, P, Drichel, D, Rossor, M, Schott, Jm, Warren, Jd, Bras, J, Guerreiro, R, Kawalia, A, Hughes, Jt, Patel, Y, Lupton, Mk, Proitsi, P, Powell, J, Kauwe, Jsk, Mancuso, M, Bonuccelli, U, Uphill, J, Fisher, E, Masullo, C, Soininen, H, Bisceglio, G, Ma, L, Dickson, Dw, Graff‐radford, Nr, Carrasquillo, Mm, Younkin, Sg, Sandro Sorbi, S, Daniilidou, M, Hodges, A, Galimberti, D, Scarpini, E, Scherer, M, Peters, O, Ramirez, A, Leber, M, Pichler, S, Mayhaus, M, Gu, W, Riemenschneider, M, Wiltfang, J, Heun, R, Kölsch, H, Kornhuber, J, Heuser, I, Rujescu, D, Hartmann, Am, Giegling, I, Hüll, M, Lovestone, S, Cruchaga, C, Morris, J, Mayo, K, Feulner, T, Sussams, R, Holmes, C, Mann, D, Pickering‐brown, S, Hooper, Nm, Mcquillin, A, Livingston, G, Bass, Nj, Vronskaya, M, Morgan, T, Denning, N, Cushion, Td, Jones, L, Marshall, R, Meggy, A, Menzies, G, Grozeva, D, O'Donovan, Mc, Owen, Mj, Holmans, Pa, Salani, F, Russo, G, Maier, W, Jessen, F, Wichmann, H-E, Morgan, K, Goate, Am, Vellas, B, Vardy, E, Moebus, S, Jöckel, K-H, Dichgans, M, Klopp, N, Turton, J, Lord, J, Brown, K, Medway, C, Nöthen, Mm, Hoffmann, P, Daniele, A, Bayer, A, Gallacher, J, van den Bussche, H, Brayne, C, Riedel‐heller, S, Powell, Jf, Al‐chalabi, A, Shaw, Ce, Kloszewska, I, Pastor, P, Diez‐fairen, M, Lynch, A, Lawlor, B, Gill, M, Coto, E, Alvarez, V, Singleton, Ab, Collinge, J, Mead, S, Ryan, N, Nacmias, B, Ortega‐cubero, S, Rodriguez‐rodriguez, E, Sanchez‐juan, P, Shofany, J, Banaj, N, Ciullo, V, Sacchinelli, E, Robert, Clarke, A David Smith, Donald, Warden, Yoav, Ben‐shlomo, Chiara, Cupidi, Raffaele Giovanni Maletta, Runi, Gallo, M, Harold, D, Cecchetti, R, Mecocci, P, Boccardi, V, Warner, N, Wilcock, G, Deloukas, P, Gwilliam, R, Corcoran, C, Tschanz, J, Munger, R., and Consortium, Gerad
Subjects: Male, Multifactorial Inheritance, Polygenic risk, Alzheimer's disease, hazard score, Polymorphism, Single Nucleotide, Settore MED/26 - NEUROLOGIA, Apolipoproteins E, Alzheimer Disease, Risk Factors, Case-Control Studies, Humans, Female, Genetic Predisposition to Disease, Research Articles, Research Article, Genome-Wide Association Study, Proportional Hazards Models
Abstract: Objective: Genome‐wide association studies (GWAS) have identified over 30 susceptibility loci associated with Alzheimer's disease (AD). Using AD GWAS data from the International Genomics of Alzheimer's Project (IGAP), Polygenic Risk Score (PRS) was successfully applied to predict life time risk of AD development. A recently introduced Polygenic Hazard Score (PHS) is able to quantify individuals with age‐specific genetic risk for AD. The aim of this study was to quantify the age‐specific genetic risk for AD with PRS and compare the results generated by PRS with those from PHS. Methods: Quantification of individual differences in age‐specific genetic risk for AD identified by the PRS, was performed with Cox Regression on 9903 (2626 cases and 7277 controls) individuals from the Genetic and Environmental Risk in Alzheimer's Disease consortium (GERAD). Polygenic Hazard Scores were generated for the same individuals. The age‐specific genetic risk for AD identified by the PRS was compared with that generated by the PHS. This was repeated using varying SNPs P‐value thresholds for disease association. Results: Polygenic Risk Score significantly predicted the risk associated with age at AD onset when SNPs were preselected for association to AD at P ≤ 0.001. The strongest effect (B = 0.28, SE = 0.04, P = 2.5 × 10−12) was observed for PRS based upon genome‐wide significant SNPs (P ≤ 5 × 10−8). The strength of association was weaker with less stringent SNP selection thresholds. Interpretation: Both PRS and PHS can be used to predict an age‐specific risk for developing AD. The PHS approach uses SNP effect sizes derived with the Cox Proportional Hazard Regression model. When SNPs were selected based upon AD GWAS case/control P ≤ 10−3, we found no advantage of using SNP effects sizes calculated with the Cox Proportional Hazard Regression model in our study. When SNPs are selected for association with AD risk at P > 10−3, the age‐specific risk prediction results are not significant for either PRS or PHS. However PHS could be more advantageous than PRS of age specific AD risk predictions when SNPs are prioritized for association with AD age at onset (i.e., powerful Cox Regression GWAS study).
Published: 2019

16. Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia

Author: Bonham, L.W., Steele, N.Z.R., Karch, C.M., Broce, I., Geier, E.G., Wen, N.L., Momeni, P., Hardy, J., Miller, Z.A., Gorno-Tempini, M.L., Hess, C.P., Lewis, P., Miller, B.L., Seeley, W.W., Manzoni, C., Desikan, R.S., Baranzini, S.E., Ferrari, R., Yokoyama, J.S., Hernandez, D.G., Nalls, M.A., Rohrer, J.D., Ramasamy, A., Kwok, J.B.J., Dobson-Stone, C., Schofield, P.R., Halliday, G.M., Hodges, J.R., Piguet, O., Bartley, L., Thompson, E., Haan, E., Hernández, Isabel, Ruiz, A., Boada, M., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N.J., Benussi, L., Binetti, G., Ghidoni, R., Forloni, G., Albani, Diego, Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Clarimón, J., Lleó, Alberto, Blesa, R., Landqvist Waldö, M., Nilsson, K., Nilsson, C., Mackenzie, I.R.A., Hsiung, G.Y.R., Mann, D.M.A., Grafman, J., Morris, C.M., Attems, J., Griffiths, T.D., McKeith, I.G., Thomas, A.J., Pietrini, P., Huey, E.D., Wassermann, E.M., Baborie, A., Jaros, E., Tierney, M.C., Pastor, Pau, Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J.B., Schlachetzki, J.C.M., Uphill, J., Collinge, J., Mead, S., Danek, A., Van Deerlin, V.M., Grossman, M., Trojanowski, J.Q., van der Zee, J., Cruts, M., Van Broeckhoven, C., Cappa, S.F., Leber, I., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, Sandro, Bagnoli, S., Piaceri, I., Nielsen, J.E., Hjermind, L.E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M.N., Fox, N.C., Warren, J.D., Spillantini, M.G., Morris, H.R., Rizzu, P., Heutink, P., Snowden, J.S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A.C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M.E., Smirne, N., Rademakers, R., Baker, M., Dickson, Dennis W., Graff-Radford, N.R., Petersen, R.C., Knopman, D., Josephs, K.A., Boeve, B.F., Parisi, J.E., Karydas, A.M., Rosen, H., van Swieten, J.C., Dopper, E.G.P., Seelaar, H., Pijnenburg, Y.A.L., Scheltens, Philip, Logroscino, G., Capozzo, R., Novelli, V., Puca, A.A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H.H., Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A.B., Universitat Autònoma de Barcelona, Broce, Iris [0000-0003-4932-1430], Miller, Zachary A. [0000-0002-5991-3053], Lewis, Patrick [0000-0003-4537-0489], Baranzini, Sergio E. [0000-0003-0067-194X], Apollo - University of Cambridge Repository, Int FTD-Genomics Consortium, Neurology, Amsterdam Neuroscience - Neurodegeneration, Divisions, and CCA - Imaging and biomarkers
Subjects: 0301 basic medicine, Aging, Transcription, Genetic, Gene regulatory network, lcsh:Medicine, Genome-wide association study, Apoptosis, Neurodegenerative, Primary progressive aphasia, Cohort Studies, 0302 clinical medicine, 692/617/375/132, Risk Factors, Databases, Genetic, 2.1 Biological and endogenous factors, Gene Regulatory Networks, Protein Interaction Maps, Aetiology, lcsh:Science, Multidisciplinary, Neurodegeneration, Neurodegenerative diseases, article, Frontotemporal lobar degeneration, 631/208/205, Single Nucleotide, Phenotype, ddc, 3. Good health, DNA-Binding Proteins, Frontotemporal Dementia (FTD), 692/617/375/365, Neurological, Medical genetics, 38/39, Engineering sciences. Technology, Transcription, Biotechnology, medicine.medical_specialty, Computational biology, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Databases, Rare Diseases, Genetic, medicine, Aphasia, Acquired Cognitive Impairment, Genetics, Humans, Primary Progressive Nonfluent Aphasia, Polymorphism, Gene, Genetic association study, International FTD-Genomics Consortium, lcsh:R, Human Genome, Neurosciences, medicine.disease, Brain Disorders, 631/208/199, 030104 developmental biology, Gene Expression Regulation, RNA, lcsh:Q, Dementia, Gene expression, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
Published: 2019

17. Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Author: Sims, R., van der Lee, S.J., Naj, A.C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B.W., Boland, A., Raybould, R., Bis, J.C., Martin, E.R., Grenier-Boley, B., Heilmann-Heimbach, S., Chouraki, V., Kuzma, A.B., Sleegers, K., Vronskaya, M., Ruiz, A., Graham, R.R., Olaso, R., Hoffmann, P., Grove, M.L., Vardarajan, B.N., Hiltunen, M., Nöthen, M.M., White, C.C., Hamilton-Nelson, K.L., Epelbaum, J., Maier, W., Choi, S.H., Beecham, G.W., Dulary, C., Herms, S., Smith, A.V., Funk, C.C., Derbois, Forstner, A.J., Ahmad, S., Li, H., Bacq, D., Harold, D., Satizabal, C.L., Valladares, O., Squassina, A., Thomas, R., Brody, J.A., Qu, L., Sánchez-Juan, P., Morgan, T., Wolters, F.J., Zhao, Y., Garcia, F.S., Denning, N., Fornage, M., Malamon, J., Naranjo, M.C.D., Majounie, E., Mosley, T.H., Dombroski, B., Wallon, D., Lupton, M.K., Dupuis, J., Whitehead, P., Fratiglioni, L., Medway, C., Jian, X., Mukherjee, S., Keller, L., Brown, K., Lin, H., Cantwell, L.B., Panza, F., McGuinness, B., Moreno-Grau, S., Burgess, J.D., Solfrizzi, V., Proitsi, P., Adams, H.H., Allen, M., Seripa, D., Pastor, P., Cupples, L.A., Price, N.D., Hannequin, D., Frank-García, A., Levy, D., Chakrabarty, P., Caffarra, P., Giegling, I., Beiser, A.S., Giedraitis, V., Hampel, H., Garcia, M.E., Wang, X., Lannfelt, L., Mecocci, P., Eiriksdottir, G., Crane, P.K., Pasquier, F., Boccardi, V., Henández, I., Barber, R.C., Scherer, M., Tarraga, L., Adams, P.M., Leber, M., Chen, Y., Albert, M.S., Riedel-Heller, S., Emilsson, V., Beekly, D., Braae, A., Schmidt, R., Blacker, D., Masullo, C., Schmidt, H., Doody, R.S., Spalletta, G., Longstreth, W.T., Jr., Fairchild, T.J., Bossù, P., Lopez, O.L., Frosch, M.P., Sacchinelli, E., Ghetti, B., Yang, Q., Huebinger, R.M., Jessen, F., Li, S., Kamboh, M.I., Morris, J., Sotolongo-Grau, O., Katz, M.J., Corcoran, C., Dunstan, M., Braddel, A., Thomas, C., Meggy, A., Marshall, R., Gerrish, A., Chapman, J., Aguilar, M., Taylor, S., Hill, M., Fairén, M.D., Hodges, A., Vellas, B., Soininen, H., Kloszewska, I., Daniilidou, M., Uphill, J., Patel, Y., Hughes, J.T., Lord, J., Turton, J., Hartmann, A.M., Cecchetti, R., Fenoglio, C., Serpente, M., Arcaro, M., Caltagirone, C., Orfei, M.D., Ciaramella, A., Pichler, S., Mayhaus, M., Gu, W., Lleó, A., Fortea, J., Blesa, R., Barber, I.S., Brookes, K., Cupidi, C., Maletta, R.G., Carrell, D., Sorbi, S., Moebus, S., Urbano, M., Pilotto, A., Kornhuber, J., Bosco, P., Todd, S., Craig, D., Johnston, J., Gill, M., Lawlor, B., Lynch, A., Fox, N.C., Hardy, J., Albin, R.L., Apostolova, L.G., Arnold, S.E., Asthana, S., Atwood, C.S., Baldwin, C.T., Barnes, L.L., Barral, S., Beach, T.G., Becker, J.T., Bigio, E.H., Bird, T.D., Boeve, B.F., Bowen, J.D., Boxer, A., Burke, J.R., Burns, J.M., Buxbaum, J.D., Cairns, N.J., Cao, C., Carlson, C.S., Carlsson, C.M., Carney, R.M., Carrasquillo, M.M., Carroll, S.L., Diaz, C.C., Chui, H.C., Clark, D.G., Cribbs, D.H., Crocco, E.A., DeCarli, C., Dick, M., Duara, R., Evans, D.A., Faber, K.M., Fallon, K.B., Fardo, D.W., Farlow, M.R., Ferris, S., Foroud, T.M., Galasko, D.R., Gearing, M., Geschwind, D.H., Gilbert, J.R., Graff-Radford, N.R., Green, R.C., Growdon, J.H., Hamilton, R.L., Harrell, L.E., Honig, L.S., Huentelman, M.J., Hulette, C.M., Hyman, B.T., Jarvik, G.P., Abner, E., Jin, L.W., Jun, G., Karydas, A., Kaye, J.A., Kim, R., Kowall, N.W., Kramer, J.H., LaFerla, F.M., Lah, J.J., Leverenz, J.B., Levey, A.I., Li, G., Lieberman, A.P., Lunetta, K.L., Lyketsos, C.G., Marson, D.C., Martiniuk, F., Mash, D.C., Masliah, E., McCormick, W.C., McCurry, S.M., McDavid, A.N., McKee, A.C., Mesulam, M., Miller, B.L., Miller, C.A., Miller, J.W., Morris, J.C., Murrell, J.R., Myers, A.J., O'Bryant, S., Olichney, J.M., Pankratz, V.S., Parisi, J.E., Paulson, H.L., Perry, W., Peskind, E., Pierce, A., Poon, W.W., Potter, H., Quinn, J.F., Raj, A., Raskind, M., Reisberg, B., Reitz, C., Ringman, J.M., Roberson, E.D., Rogaeva, E., Rosen, H.J., Rosenberg, R.N., Sager, M.A., Saykin, A.J., Schneider, J.A., Schneider, L.S., Seeley, W.W., Smith, A.G., Sonnen, J.A., Spina, S., Stern, R.A., Swerdlow, R.H., Tanzi, R.E., Thornton-Wells, T.A., Trojanowski, J.Q., Troncoso, J.C., Van Deerlin, V.M., Van Eldik, L.J., Vinters, H.V., Vonsattel, J.P., Weintraub, S., Welsh-Bohmer, K.A., Wilhelmsen, K.C., Williamson, J., Wingo, T.S., Woltjer, R.L., Wright, C.B., Yu, C.E., Yu, L., Garzia, F., Golamaully, F., Septier, G., Engelborghs, S., Vandenberghe, R., De Deyn, P.P., Fernadez, C.M., Benito, Y.A., Thonberg, H., Forsell, C., Lilius, L., Kinhult-Stählbom, A., Kilander, L., Brundin, R., Concari, L., Helisalmi, S., Koivisto, A.M., Haapasalo, A., Dermecourt, V., Fievet, N., Hanon, O., Dufouil, C., Brice, A., Ritchie, K., Dubois, B., Himali, J.J., Keene, C.D., Tschanz, J., Fitzpatrick, A.L., Kukull, W.A., Norton, M., Aspelund, T., Larson, E.B., Munger, R., Rotter, J.I., Lipton, R.B., Bullido, M.J., Hofman, A., Montine, T.J., Coto, E., Boerwinkle, E., Petersen, R.C., Alvarez, V., Rivadeneira, F., Reiman, E.M., Gallo, M., O'Donnell, C.J., Reisch, J.S., Bruni, A.C., Royall, D.R., Dichgans, M., Sano, M., Galimberti, D., St George-Hyslop, P., Scarpini, E., Tsuang, D.W., Mancuso, M., Bonuccelli, U., Winslow, A.R., Daniele, A., Wu, C.K., Peters, O., Nacmias, B., Riemenschneider, M., Heun, R., Brayne, C., Rubinsztein, D.C., Bras, J., Guerreiro, R., Al-Chalabi, A., Shaw, C.E., Collinge, J., Mann, D., Tsolaki, M., Clarimón, J., Sussams, R., Lovestone, S., O'Donovan, M.C., Owen, M.J., Behrens, T.W., Mead, S., Goate, A.M., Uitterlinden, A.G., Holmes, C., Cruchaga, C., Ingelsson, M., Bennett, D.A., Powell, J., Golde, T.E., Graff, C., De Jager, P.L., Morgan, K., Ertekin-Taner, N., Combarros, O., Psaty, B.M., Passmore, P., Younkin, S.G., Berr, C., Gudnason, V., Rujescu, D., Dickson, D.W., Dartigues, J.F., DeStefano, A.L., Ortega-Cubero, S., Hakonarson, H., Campion, D., Boada, M., Kauwe, J.K., Farrer, L.A., Van Broeckhoven, C., Ikram, M.A., Jones, L., Haines, J.L., Tzourio, C., Launer, L.J., Escott-Price, V., Mayeux, R., Deleuze, J.F., Amin, N., Holmans, P.A., Pericak-Vance, M.A., Amouyel, P., van Duijn, C.M., Ramirez, A., Wang, L.S., Lambert, J.C., Seshadri, S., Williams, J., Schellenberg, G.D., Peloso, Gina M., van der Lee, Sven J., Destefano, Anita L., and Seshardi, Sudha
Published: 2018
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18. CXCR4involvement in neurodegenerative diseases

Author: Bonham, Luke W, Karch, Celeste M, Ferrari, Raffaele, Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., van der Zee, J., Cruts, M., Van Broeckhoven, C., Cappa, S. F., Leber, I., Hannequin, D., Hardy, John, Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Momeni, Parastoo, Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Höglinger, Günter, Rizzu, P., Heutink, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Maletta, R., Frangipane, F., Cupidi, C., Müller, Ulrich, Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Rademakers, R., Baker, M., Dickson, D. W., Graff-Radford, N. R., Petersen, R. C., Hess, Christopher P, Knopman, D., Josephs, K. A., Boeve, B. F., Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., van Swieten, J. C., Dopper, E. G. P., Sugrue, Leo P, Seelaar, H., Pijnenburg, Y. A. L., Scheltens, P., Logroscino, G., Capozzo, R., Novelli, V., Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Dillon, William P, Sorrentino, P., Kristiansen, M., Chiang, H-H, Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Schellenberg, Gerard D, Pickering-Brown, S., Singleton, A. B., Hardy, J., Momeni, P., Miller, Bruce L, Fan, Chun C, Andreassen, Ole A, Dale, Anders M, Barkovich, A James, Yokoyama, Jennifer S, Desikan, Rahul S, Consortium, International FTD-Genomics, Consortium, International Parkinson’s Disease Genetics, Project, International Genomics of Alzheimer’s, Ferrari, R., Hernandez, D. G., Tan, Chin, Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Geier, Ethan G, Thompson, E., Haan, E., Hernández, I., Ruiz, A., Boada, M., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Wang, Yunpeng, Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Clarimón, J., Lleó, A., Wen, Natalie, Blesa, R., Waldö, M Landqvist, Nilsson, K., Nilsson, C., Mackenzie, I. R. A., Hsiung, G-Y R, Mann, D. M. A., Grafman, J., Morris, C. M., Attems, J., Broce, Iris J, Griffiths, T. D., McKeith, I. G., Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Pastor, P., Li, Yi, Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Barkovich, Matthew J, Rogaeva, E., George-Hyslop, P St, Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C. M., Uphill, J., Collinge, J., Mead, S., Bonham, Luke W., Karch, Celeste M., Fan, Chun C., Tan, Chin, Geier, Ethan G., Wang, Yunpeng, Wen, Natalie, Broce, Iris J., Li, Yi, Barkovich, Matthew J., Ferrari, Raffaele, Hardy, John, Momeni, Parastoo, Höglinger, Günter, Müller, Ulrich, Hess, Christopher P., Sugrue, Leo P., Dillon, William P., Schellenberg, Gerard D., Miller, Bruce L., Andreassen, Ole A., Dale, Anders M., Barkovich, A. Jame, Yokoyama, Jennifer S., Desikan, Rahul S., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Haan, E., Hernández, I., Ruiz, A., Boada, M., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Clarimón, J., Lleó, A., Blesa, R., Waldö, M. Landqvist., Nilsson, K., Nilsson, C., Mackenzie, I. R. A., Hsiung, G. -Y. R., Mann, D. M. A., Grafman, J., Morris, C. M., Attems, J., Griffiths, T. D., Mckeith, I. G., Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Pastor, P., Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., George-Hyslop, P. St., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C. M., Uphill, J., Collinge, J., Mead, S., Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., Van Der Zee, J., Cruts, M., Van Broeckhoven, C., Cappa, S. F., Leber, I., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Heutink, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Rademakers, R., Baker, M., Dickson, D. W., Graff-Radford, N. R., Petersen, R. C., Knopman, D., Josephs, K. A., Boeve, B. F., Parisi, J. E., Seeley, W. W., Karydas, A. M., Rosen, H., Van Swieten, J. C., Dopper, E. G. P., Seelaar, H., Pijnenburg, Y. A. L., Scheltens, P., Logroscino, G., Capozzo, R., Novelli, V., Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H. -H., Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A. B., Rademakers, Rosa, International FTD-Genomics Consortium (IFGC), International Parkinsons Disease Genetics Consortium (IPDGC), and International Genomics of Alzheimers Project (IGAP)
Subjects: 0301 basic medicine, Aging, Gene Expression, Genome-wide association study, metabolism [Microglia], Neurodegenerative, Bioinformatics, Alzheimer's Disease, Transgenic, Mice, 0302 clinical medicine, Risk Factors, Receptors, 2.1 Biological and endogenous factors, Psychology, Gene Regulatory Networks, Aetiology, Alzheimer's Disease Related Dementias (ADRD), 0303 health sciences, Gene Regulatory Network, Parkinson's Disease, International Genomics of Alzheimer’s Project, Neurodegeneration, Brain, Neurodegenerative Diseases, Single Nucleotide, International Parkinson’s Disease Genetics Consortium, Frontotemporal Dementia (FTD), Psychiatry and Mental Health, Neurological, Public Health and Health Services, Tauopathy, Microglia, Frontotemporal dementia, Human, Receptors, CXCR4, Tau protein, Clinical Sciences, Mice, Transgenic, Computational biology, Biology, Polymorphism, Single Nucleotide, Article, CXCR4 protein, human, Progressive supranuclear palsy, lcsh:RC321-571, Cellular and Molecular Neuroscience, 03 medical and health sciences, Rare Diseases, Text mining, Genetic predisposition, medicine, Genetics, Acquired Cognitive Impairment, Animals, Humans, Genetic Predisposition to Disease, ddc:610, Polymorphism, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, 030304 developmental biology, CXCR4, Neurodegenerative Disease, Animal, business.industry, Risk Factor, International FTD-Genomics Consortium, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, genetics [Receptors, CXCR4], Brain Disorders, Genome-Wide Association Study, 030104 developmental biology, metabolism [Brain], genetics [Neurodegenerative Diseases], Expression quantitative trait loci, biology.protein, Dementia, Human medicine, metabolism [Receptors, CXCR4], business, 030217 neurology & neurosurgery
Abstract: Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson’s disease (PD) and Alzheimer’s disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12, TLR2, RALB, and CCR5. Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a ‘network’ of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases.
Published: 2017

19. Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

Author: Hagenaars, Sp, Radaković, R, Crockford, C, Fawns-Ritchie, C, Gale, Cr, Deary, Ij, J B, J Kwok, Dobson-Stone, C, R Schofield, P, Gmhalliday, R Hodges, J, Piguet, O, Bartley, L, Thompson, E, Hernaândez, I, Ruiz, A, Mboada, Borroni, B, Padovani, A, Cruchaga, C, J Cairns, N, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimoân, J, Lleoâ, A, Blesa, R, Mlandqvist, Waldoè, Nilsson, K, Nilsson, C, I R, A Mackenzie, G-Y, R Hsiung, Dma, Mann, Grafman, J, Cmmorris, Attems, J, D Griffiths, T, G McKeith, I, J Thomas, A, Pietrini, P, D Huey, E, Emwassermann, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, P St George-Hyslop, Rossi, G, Tagliavini, F, Giaccone, G, B Rowe, J, Cmschlachetzki, J, Uphill, J, Collinge, J, Mead, S, Danek, A, Vmvan, Deerlin, Mgrossman, Q Trojanowski, J, J van der Zee, C Van Broeckhoven, F Cappa, S, Leber, I, Hannequin, D, Golfier, V, Mvercelletto, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, E Nielsen, J, E Hjermind, L, Mriemenschneider, Mmayhaus, Ibach, B, Gasparoni, G, Pichler, S, Wgu, Rossor, Mn, C Fox, N, D Warren, J, Spillantini, Mg, R Morris, H, Rizzu, P, Heutink, P, S Snowden, J, Rollinson, S, Richardson, A, Gerhard, A, C Bruni, A, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Manfossi, Mgallo, Conidi, Me, Smirne, N, Rademakers, R, Baker, M, Dwdickson, R Graff-Radford, N, C Petersen, R, Knopman, D, A Josephs, K, F Boeve, B, E Parisi, J, Wwseeley, L Miller, B, Amkarydas, Rosen, H, C van Swieten, J, E G, P Dopper, Seelaar, H, Y A, L Pijnenburg, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, A Puca, A, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Mkristiansen, H-H, Chiang, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, B Singleton, A, Hardy, J, and Momeni., P
Subjects: Genetics and Molecular Biology (all), Multifactorial Inheritance, Peak Expiratory Flow Rate, Disease, Physical function, Alzheimer's Disease, Biochemistry, Motor Neuron Diseases, 0302 clinical medicine, Cognition, Learning and Memory, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Forced Expiratory Volume, Medicine and Health Sciences, Amyotrophic lateral sclerosis, Genetic risk, Cognitive Impairment, 0303 health sciences, Cognitive Neurology, Neurodegenerative Diseases, Middle Aged, Mental Status and Dementia Tests, Neurology, Frontotemporal Dementia, Clinical psychology, Frontotemporal dementia, Research Article, Adult, Cognitive Neuroscience, Risk Assessment, 03 medical and health sciences, Memory, Alzheimer Disease, Mental Health and Psychiatry, mental disorders, medicine, Genetics, Humans, Effects of sleep deprivation on cognitive performance, Muscle Strength, Genetic Association Studies, 030304 developmental biology, Aged, business.industry, Amyotrophic Lateral Sclerosis, Biology and Life Sciences, medicine.disease, United Kingdom, Physical Fitness, Genetics of Disease, Cognitive Science, Polygenic risk score, Dementia, business, 030217 neurology & neurosurgery, Neuroscience, Genome-Wide Association Study
Abstract: INTRODUCTIONIt is unclear whether polygenic risk for neurodegenerative disease is associated with cognitive performance and physical health.METHODSThis study tested whether polygenic scores for Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) are associated with cognitive performance and physical health. Group-based analyses were performed to compare associations with cognitive and physical function outcomes in the top and bottom 10% for the three neurodegenerative polygenic risk scores.RESULTSHigher polygenic risk scores for AD, ALS, and FTD were associated with lower cognitive performance. Higher polygenic risk scores for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS.DISCUSSIONOur results suggest overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health.
Published: 2018

20. The genetic prehistory of the Greater Caucasus

Author: Wang, C., Reinhold, S., Kalmykov, A., Wissgott, A., Brandt, G., Jeong, C., Cheronet, O., Ferry, M., Harney, E., Keating, D., Mallick, S., Rohland, N., Stewardson, K., Kantorovich, A., Maslov, V., Petrenko, V., Erlikh, V., Atabiev, B., Magomedov, R., Kohl, P., Alt, K., Pichler, S., Gerling, C., Meller, H., Vardanyan, B., Yeganyan, L., Rezepkin, A., Mariaschk, D., Berezina, N., Gresky, J., Fuchs, K., Knipper, C., Schiffels, S., Balanovska, E., Balanovsky, O., Mathieson, I., Higham, T., Berezin, Y., Buzhilova, A., Trifonov, V., Pinhasi, R., Belinskiy, A., Reich, D., Hansen, S., Krause, J., and Haak, W.
Abstract: Archaeogenetic studies have described the formation of Eurasian ’}steppe ancestry{’ as a mixture of Eastern and Caucasus hunter-gatherers. However, it remains unclear when and where this ancestry arose and whether it was related to a horizon of cultural innovations in the 4th millennium BCE that subsequently facilitated the advance of pastoral societies likely linked to the dispersal of Indo-European languages. To address this, we generated genome-wide SNP data from 45 prehistoric individuals along a 3000-year temporal transect in the North Caucasus. We observe a genetic separation between the groups of the Caucasus and those of the adjacent steppe. The Caucasus groups are genetically similar to contemporaneous populations south of it, suggesting that - unlike today - the Caucasus acted as a bridge rather than an insurmountable barrier to human movement. The steppe groups from Yamnaya and subsequent pastoralist cultures show evidence for previously undetected Anatolian farmer-related ancestry from different contact zones, while Steppe Maykop individuals harbour additional Upper Palaeolithic Siberian and Native American related ancestry.
Published: 2018

21. Meta-analysis of genetic association with diagnosed Alzheimer's disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing

Author: Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Naj, AC, Boland, A, Vronskaya, M, van der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Aloso, R, Raybould, R, Chen, Y, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, L, Bacq, D, Denning, N, Jian, X, Zhao, Y, Zompo, MD, Fox, NC, Grove, ML, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Garcia, FS, Patel, Y, Brody, JA, Dombroski, B, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewics, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, W, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Pichler, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Fernadez, CM, Sussams, R, Lin, H, Fairchild, TJ, Benito, YA, Holmes, C, Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roschupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernández, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth Jr, WT, Montine, TJ, Frisardi, V, Ortega-Cubero, S, Rivadeneira, F, Petersen, RC, Deramecourt, V, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Caltagirone, C, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AG, Royall, DR, Dufouil, C, Maletta, RG, Moreno-Grau, S, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Baldwin, CT, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frölich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JI, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, JR, Kauwe, JK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, C, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Cribbs, DH, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hüll, M, Geschwind, DH, Gilbert, JR, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, G, Jin, LW, Leonenko, G, Jun, G, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jöckel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nöthen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, McKee, AC, van den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O’Bryant, S, Coto, E, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, W, Mead, S, Peskind, E, Rosser, M, Pierce, A, Ryan, N, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Bossù, P, Reisberg, B, Clarke, R, Reitz, C, Smith, AD, Ringman, JM, Warden, D, Roberson, ED, Wilcock, G, Rogaeva, E, Bruni, AC, Rosen, HJ, Gallo, M, Rosenberg, RN, Ben-Shlomo, Y, Sager, MA, Mecocci, P, Saykin, AJ, Pastor, P, Cuccaro, ML, Vance, JM, Schneider, JA, Schneider, LS, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tanzi, RE, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, CE, Yu, L, Crane, PK, Bennett, DA, Boccardi, V, De Jager, PL, Warner, N, Lopez, OL, McDonough, S, Ingelsson, M, Deloukas, P, Cruchaga, C, Graff, C, Gwilliam, R, Fornage, M, Goate, AM, Sanchez-Juan, P, Kehoe, PG, Amin, N, Ertekin-Taner, N, Berr, C, Debette, S, Love, S, Launer, LJ, Younkin, SG, Dartigues, JF, Corcoran, C, Ikram, MA, Dickson, DW, Campion, D, Tschanz, J, Schmidt, H, Hakonarson, H, Munger, R, Schmidt, R, Farrer, LA, Van Broeckhoven, C, O’Donovan, MC, DeStefano, AL, Jones, L, Haines, JL, Deleuze, JF, Owen, MJ, Gudnason, V, Mayeux, R, Escott-Price, V, Psaty, BM, Ruiz, A, Ramirez, A, Wang, LS, van Duijn, CM, Holmans, PA, Seshadri, S, Williams, J, Amouyel, P, Schellenberg, GD, Lambert, JC, Pericak-Vance, MA, Bis, JC [0000-0002-3409-1110], Garnier, JG [0000-0003-4991-763X], Smith, AV [0000-0001-9088-234X], Denning, N [0000-0001-8467-7382], Vandenberghe, R [0000-0001-6237-2502], Himali, JJ [0000-0003-1391-9481], Rodriguez-Rodriguez, E [0000-0001-7742-677X], Frisardi, V [0000-0003-0764-7387], Ortega-Cubero, S [0000-0003-0520-9439], Hanon, O [0000-0002-4697-122X], Brice, A [0000-0002-0941-3990], Albin, RL [0000-0002-0629-608X], Buxbaum, JD [0000-0001-8898-8313], Bass, NJ [0000-0002-4481-778X], Fisher, E [0000-0003-2850-9936], Bayer, A [0000-0002-7514-248X], Gallacher, J [0000-0002-2394-5299], Brayne, C [0000-0001-5307-663X], Riedel-Heller, S [0000-0003-4321-6090], Al-Chalabi, A [0000-0002-4924-7712], and Apollo - University of Cambridge Repository
Subjects: Aging, 4202 Epidemiology, Genome-wide association study, Disease, Neurodegenerative, Biology, 3101 Biochemistry and Cell Biology, Alzheimer's Disease, 3105 Genetics, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Acquired Cognitive Impairment, Genetics, medicine, 2.1 Biological and endogenous factors, Dementia, Gene, 030304 developmental biology, Genetic association, 2 Aetiology, 0303 health sciences, Prevention, Human Genome, 42 Health Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Lipid metabolism, medicine.disease, Brain Disorders, 3. Good health, Meta-analysis, Neurological, Alzheimer's disease, 030217 neurology & neurosurgery, 31 Biological Sciences
Abstract: IntroductionLate-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly1, and risk is partially driven by genetics2. Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS)3–8. To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci (IQCK, ACE, ADAM10, and ADAMTS1). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7) indicating that additional rare variants remain to be identified.
Published: 2018
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22. Protein network analysis reveals selectively vulnerable regions and biological processes in FTD

Author: Bonham, Lw1, Steele, Nzr1, Karch, Cm1, Manzoni, C1, Geier, Eg1, Wen, N1, Ofori-Kuragu, A1, Momeni, P1, Hardy, J1, Miller, Za1, Hess, Cp1, Lewis, P1, Miller, Bl1, Seeley, Ww1, Baranzini, Se1, Desikan, Rs1, Ferrari, R1, Yokoyama, Js1, ( Ferrari R, International FTD-Genomics Consortium, Hernandez, Dg, Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jbj, Dobson-Stone, C, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Landqvist Waldö, M, Nilsson, C, Mackenzie, Ira, Hsiung, Gyr, Mann, Dma, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wassermann, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jcm, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin VM, Grossman, M, Trojanowski, Jq, van der Zee, J, Cruts, M, Van Broeckhoven, C, Cappa, Sf, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Spillantini, Mg, Morris, Hr, Rizzu, P, Heutink, P, Snowden, Js, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, Me, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff-Radford, Nr, Petersen, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Miller, Bl, Karydas, Am, Rosen, H, van Swieten JC, Dopper, Eg, Seelaar, H, Pijnenburg, Yal, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, Ab, Hardy, J, and Momeni, P.
Subjects: 0301 basic medicine, Cell type, Disease, Frontotemporal lobar degeneration, Biology, medicine.disease, Article, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Interaction network, Genetic variation, medicine, Neurology (clinical), Gene, Neuroscience, 030217 neurology & neurosurgery, Genetics (clinical), Frontotemporal dementia, Genetic association
Abstract: ObjectiveThe neuroanatomical profile of behavioral variant frontotemporal dementia (bvFTD) suggests a common biological etiology of disease despite disparate pathologic causes; we investigated the genetic underpinnings of this selective regional vulnerability to identify new risk factors for bvFTD.MethodsWe used recently developed analytical techniques designed to address the limitations of genome-wide association studies to generate a protein interaction network of 63 bvFTD risk genes. We characterized this network using gene expression data from healthy and diseased human brain tissue, evaluating regional network expression patterns across the lifespan as well as the cell types and biological processes most affected in bvFTD.ResultsWe found that bvFTD network genes show enriched expression across the human lifespan in vulnerable neuronal populations, are implicated in cell signaling, cell cycle, immune function, and development, and are differentially expressed in pathologically confirmed frontotemporal lobar degeneration cases. Five of the genes highlighted by our differential expression analyses, BAIAP2, ERBB3, POU2F2, SMARCA2, and CDC37, appear to be novel bvFTD risk loci.ConclusionsOur findings suggest that the cumulative burden of common genetic variation in an interacting protein network expressed in specific brain regions across the lifespan may influence susceptibility to bvFTD.
Published: 2018

23. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer’s and Parkinson’s diseases

Author: Ferrari R, Wang Y, Vandrovcova J, Guelfi S, Witeolar A, Karch CM, Schork AJ, Fan CC, Brewer JB, International FTD-Genomics Consortium (IFGC), International Parkinson's Disease Genomics Consortium (IPDGC), International Genomics of Alzheimer's Project (IGAP), Momeni P, Schellenberg GD, Dillon WP, Sugrue LP, Hess CP, Yokoyama JS, Bonham LW, Rabinovici GD, Miller BL, Andreassen OA, Dale AM, Hardy J, Desikan RS, Collaborators: Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JBJ, Dobson-Stone C, Schofield PR, Halliday GM, Hodges JR, Piguet O, Bartley L, Thompson E, Haan E, Hernández I, Ruiz A, Boada M, Borroni B, Padovani A, Cruchaga C, Cairns NJ, Benussi L, Binetti G, Ghidoni R, Forloni G, Albani D, Galimberti D, Fenoglio C, Serpente M, Scarpini E, Clarimón J, Lleó A, Blesa R, Landqvist Waldö M, Nilsson C, Mackenzie IRA, Hsiung GYR, Mann DMA, Grafman J, Morris CM, Attems J, Griffiths TD, McKeith IG, Thomas AJ, Pietrini P, Huey ED, Wassermann EM, Baborie A, Jaros E, Tierney MC, Pastor P, Razquin C, Ortega-Cubero S, Alonso E, Perneczky R, Diehl-Schmid J, Alexopoulos P, Kurz A, Rainero I, Rubino E, Pinessi L, Rogaeva E, St George-Hyslop P, Rossi G, Tagliavini F, Giaccone G, Rowe JB, Schlachetzki JCM, Uphill J, Collinge J, Mead S, Danek A, Van Deerlin VM, Grossman M, Trojanowski JQ, van der Zee J, Cruts M, Van Broeckhoven C, Cappa SF, Leber I, Hannequin D, Golfier V, Vercelletto M, Brice A, Nacmias B, Sorbi S, Bagnoli S, Piaceri I, Nielsen JE, Hjermind LE, Riemenschneider M, Mayhaus M, Ibach B, Gasparoni G, Pichler S, Gu W, Rossor MN, Fox NC, Warren JD, Spillantini MG, Morris HR, Rizzu P, Heutink P, Snowden JS, Rollinson S, Richardson A, Gerhard A, Bruni AC, Maletta R, Frangipane F, Cupidi C, Bernardi L, Anfossi M, Gallo M, Conidi ME, Smirne N, Rademakers R, Baker M, Dickson DW, Graff-Radford NR, Petersen RC, Knopman D, Josephs KA, Boeve BF, Parisi JE, Seeley WW, Karydas AM, Rosen H, van Swieten JC, Dopper EG, Seelaar H, Pijnenburg YAL, Scheltens P, Logroscino G, Capozzo R, Novelli V, Puca AA, Franceschi M, Postiglione A, Milan G, Sorrentino P, Kristiansen M, Chiang HH, Graff C, Pasquier F, Rollin A, Deramecourt V, Lebouvier T, Kapogiannis D, Ferrucci L, Pickering-Brown S, Singleton AB, Momeni P., Neurology, VU University medical center, Human genetics, Amsterdam Neuroscience - Neurodegeneration, CCA - Imaging and biomarkers, Divisions, Van Broeckhoven, Christine, Rademakers, Rosa, International FTD-Genomics Consortium (IFGC), International Parkinson's Disease Genomics Consortium (IPDGC), International Genomics of Alzheimer's Project (IGAP), Ferrari, R, Wang, Y, Vandrovcova, J, Guelfi, S, Witeolar, A, Karch, Cm, Schork, Aj, Fan, Cc, Brewer, Jb, International FTD-Genomics Consortium, (IFGC), International Parkinson's Disease Genomics Consortium, (IPDGC), International Genomics of Alzheimer's Project, (IGAP), Momeni, P, Schellenberg, Gd, Dillon, Wp, Sugrue, Lp, Hess, Cp, Yokoyama, J, Bonham, Lw, Rabinovici, Gd, Miller, Bl, Andreassen, Oa, Dale, Am, Hardy, J, Desikan, R, Collaborators: Ferrari, R, Hernandez, Dg, Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jbj, Dobson-Stone, C, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Landqvist Waldö, M, Nilsson, C, Mackenzie, Ira, Hsiung, Gyr, Mann, Dma, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wassermann, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jcm, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, Vm, Grossman, M, Trojanowski, Jq, van der Zee, J, Cruts, M, Van Broeckhoven, C, Cappa, Sf, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Spillantini, Mg, Morris, Hr, Rizzu, P, Heutink, P, Snowden, J, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, Me, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff-Radford, Nr, Petersen, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Karydas, Am, Rosen, H, van Swieten, Jc, Dopper, Eg, Seelaar, H, Pijnenburg, Yal, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, Ab, and Momeni, P.
Subjects: 0301 basic medicine, Genotype, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, mental disorders, Genetic Pleiotropy, Genetic predisposition, Medicine, Humans, Genetic Predisposition to Disease, Allele, Polymorphism, Biology, Alleles, Genetic association, Genetics, business.industry, Frontotemporal Dementia, Genome-Wide Association Study, Parkinson Disease, Surgery, Neurology (clinical), Psychiatry and Mental Health, Single Nucleotide, medicine.disease, Genetic architecture, nervous system diseases, 030104 developmental biology, Human medicine, business, Neuroscience, 030217 neurology & neurosurgery, Frontotemporal dementia
Abstract: Background Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer9s disease (AD) and Parkinson9s disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap between FTD, AD and PD to assess shared pathobiology and identify novel genetic variants associated with increased risk for FTD. Methods Summary statistics were obtained from the International FTD Genomics Consortium, International PD Genetics Consortium and International Genomics of AD Project (n>75 000 cases and controls). We used conjunction false discovery rate (FDR) to evaluate genetic pleiotropy and conditional FDR to identify novel FTD-associated SNPs. Relevant variants were further evaluated for expression quantitative loci. Results We observed SNPs within the HLA , MAPT and APOE regions jointly contributing to increased risk for FTD and AD or PD. By conditioning on polymorphisms associated with PD and AD, we found 11 loci associated with increased risk for FTD. Meta-analysis across two independent FTD cohorts revealed a genome-wide signal within the APOE region (rs6857, 3′-UTR= PVRL2 , p=2.21×10 –12 ), and a suggestive signal for rs1358071 within the MAPT region (intronic= CRHR1 , p=4.91×10 −7 ) with the effect allele tagging the H1 haplotype. Pleiotropic SNPs at the HLA and MAPT loci associated with expression changes in cis -genes supporting involvement of intracellular vesicular trafficking, immune response and endo/lysosomal processes. Conclusions Our findings demonstrate genetic pleiotropy in these neurodegenerative diseases and indicate that sporadic FTD is a polygenic disorder where multiple pleiotropic loci with small effects contribute to increased disease risk.
Published: 2016

24. Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Author: Peloso, Gina M., van der Lee, Sven J., Sims, R., van der Lee, S. J., Naj, A. C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B. W., Boland, A., Raybould, R., Bis, J. C., Martin, E. R., Grenier-Boley, B., Heilmann-Heimbach, S., Chouraki, V., Kuzma, A. B., Sleegers, K., Vronskaya, M., Ruiz, A., Graham, R. R., Olaso, R., Hoffmann, P., Grove, M. L., Vardarajan, B. N., Hiltunen, M., Nöthen, M. M., White, C. C., Hamilton-Nelson, K. L., Epelbaum, J., Maier, W., Choi, S. H., Beecham, G. W., Dulary, C., Herms, S., Smith, A. V., Funk, C. C., Derbois, Null, Forstner, A. J., Ahmad, S., Li, H., Bacq, D., Harold, D., Satizabal, C. L., Valladares, O., Squassina, A., Thomas, R., Brody, J. A., Qu, L., Sánchez-Juan, P., Morgan, T., Wolters, F. J., Zhao, Yu Yang, Garcia, F. S., Denning, N., Fornage, M., Malamon, J., Naranjo, M. C. D., Majounie, E., Mosley, T. H., Dombroski, B., Wallon, D., Lupton, M. K., Dupuis, J., Whitehead, P., Fratiglioni, L., Medway, C., Jian, X., Mukherjee, S., Keller, L., Brown, K., Lin, H., Cantwell, L. B., Panza, F., Mcguinness, B., Moreno-Grau, S., Burgess, J. D., Solfrizzi, V., Proitsi, P., Adams, H. H., Allen, M., Seripa, D., Pastor, P., Cupples, L. A., Price, N. D., Hannequin, D., Frank-García, A., Levy, D., Chakrabarty, P., Caffarra, P., Giegling, I., Beiser, A. S., Giedraitis, V., Hampel, H., Garcia, M. E., Wang, X., Lannfelt, L., Mecocci, P., Eiriksdottir, G., Crane, P. K., Pasquier, F., Boccardi, V., Henández, I., Barber, R. C., Scherer, M., Tarraga, L., Adams, P. M., Leber, M., Chen, Y., Albert, M. S., Riedel-Heller, S., Emilsson, V., Beekly, D., Braae, A., Schmidt, R., Blacker, D., Masullo, Carlo, Schmidt, H., Doody, R. S., Spalletta, Gianfranco, Longstreth, W. T., Fairchild, T. J., Bossù, P., Lopez, O. L., Frosch, M. P., Sacchinelli, E., Ghetti, B., Yang, Q., Huebinger, R. M., Jessen, F., Li, S., Kamboh, M. I., Morris, J., Sotolongo-Grau, O., Katz, M. J., Corcoran, C., Dunstan, M., Braddel, A., Thomas, C., Meggy, A., Marshall, R., Gerrish, A., Chapman, J., Aguilar, M., Taylor, S., Hill, M., Fairén, M. D., Hodges, A., Vellas, B., Soininen, H., Kloszewska, I., Daniilidou, M., Uphill, J., Patel, Y., Hughes, J. T., Lord, J., Turton, J., Hartmann, A. M., Cecchetti, R., Fenoglio Gaddo, Maria Cristina, Serpente, M., Arcaro, M., Caltagirone, C., Orfei, M. D., Ciaramella, A., Pichler, S., Mayhaus, M., Gu, W., Lleó, A., Fortea, J., Blesa, R., Barber, I. S., Brookes, K., Cupidi, C., Maletta, R. G., Carrell, D., Sorbi, S., Moebus, S., Urbano, M., Pilotto, A., Kornhuber, J., Bosco, P., Todd, S., Craig, D., Johnston, J., Gill, M., Lawlor, B., Lynch, A., Fox, N. C., Hardy, J., Albin, R. L., Apostolova, L. G., Arnold, S. E., Asthana, S., Atwood, C. S., Baldwin, C. T., Barnes, L. L., Barral, S., Beach, T. G., Becker, J. T., Bigio, E. H., Bird, T. D., Boeve, B. F., Bowen, J. D., Boxer, A., Burke, J. R., Burns, J. M., Buxbaum, J. D., Cairns, N. J., Cao, C., Carlson, C. S., Carlsson, C. M., Carney, R. M., Carrasquillo, M. M., Carroll, S. L., Diaz, C. C., Chui, H. C., Clark, D. G., Cribbs, D. H., Crocco, E. A., Decarli, C., Dick, M., Duara, R., Evans, D. A., Faber, K. M., Fallon, K. B., Fardo, D. W., Farlow, M. R., Ferris, S., Foroud, T. M., Galasko, D. R., Gearing, M., Geschwind, D. H., Gilbert, J. R., Graff-Radford, N. R., Green, R. C., Growdon, J. H., Hamilton, R. L., Harrell, L. E., Honig, L. S., Huentelman, M. J., Hulette, C. M., Hyman, B. T., Jarvik, G. P., Abner, E., Jin, L. W., Jun, G., Karydas, A., Kaye, J. A., Kim, R., Kowall, N. W., Kramer, J. H., Laferla, F. M., Lah, J. J., Leverenz, J. B., Levey, A. I., Li Quadri Cassini, Giancarlo, Lieberman, A. P., Lunetta, K. L., Lyketsos, C. G., Marson, D. C., Martiniuk, F., Mash, D. C., Masliah, E., Mccormick, W. C., Mccurry, S. M., Mcdavid, A. N., Mckee, A. C., Mesulam, M., Miller, B. L., Miller, C. A., Miller, J. W., Morris, J. C., Murrell, J. R., Myers, A. J., O'Bryant, S., Olichney, J. M., Pankratz, V. S., Parisi, J. E., Paulson, H. L., Perry, W., Peskind, E., Pierce, A., Poon, W. W., Potter, H., Quinn, J. F., Raj, A., Raskind, M., Reisberg, B., Reitz, C., Ringman, J. M., Roberson, E. D., Rogaeva, E., Rosen, H. J., Rosenberg, R. N., Sager, M. A., Saykin, A. J., Schneider, J. A., Schneider, L. S., Seeley, W. W., Smith, A. G., Sonnen, J. A., Spina, S., Stern, R. A., Swerdlow, R. H., Tanzi, R. E., Thornton-Wells, T. A., Trojanowski, J. Q., Troncoso, J. C., Van Deerlin, V. M., Van Eldik, L. J., Vinters, H. V., Vonsattel, J. P., Weintraub, S., Welsh-Bohmer, K. A., Wilhelmsen, K. C., Williamson, J., Wingo, T. S., Woltjer, R. L., Wright, C. B., Yu, C. E., Yu, L., Garzia, F., Golamaully, F., Septier, G., Engelborghs, S., Vandenberghe, R., De Deyn, P. P., Fernadez, C. M., Benito, Y. A., Thonberg, H., Forsell, C., Lilius, L., Kinhult-Stählbom, A., Kilander, L., Brundin, R., Concari, L., Helisalmi, S., Koivisto, A. M., Haapasalo, A., Dermecourt, V., Fievet, N., Hanon, O., Dufouil, C., Brice, A., Ritchie, K., Dubois, B., Himali, J. J., Keene, C. D., Tschanz, J., Fitzpatrick, A. L., Kukull, W. A., Norton, M., Aspelund, T., Larson, E. B., Munger, R., Rotter, J. I., Lipton, R. B., Bullido, M. J., Hofman, A., Montine, T. J., Coto, E., Boerwinkle, E., Petersen, R. C., Alvarez, V., Rivadeneira, F., Reiman, E. M., Gallo, Massimiliano, O'Donnell, C. J., Reisch, J. S., Bruni, A. C., Royall, D. R., Dichgans, M., Sano, M., Galimberti, D., St George-Hyslop, P., Scarpini, E., Tsuang, D. W., Mancuso, M., Bonuccelli, U., Daniele, Antonio, Wu, C. K., Peters, O., Nacmias, B., Riemenschneider, M., Heun, R., Brayne, C., Rubinsztein, D. C., Bras, J., Guerreiro, R., Al-Chalabi, A., Shaw, C. E., Collinge, J., Mann, D., Tsolaki, M., Clarimón, J., Sussams, R., Lovestone, S., O'Donovan, M. C., Owen, M. J., Behrens, T. W., Mead, S., Goate, A. M., Uitterlinden, A. G., Holmes, C., Cruchaga, C., Ingelsson, M., Bennett, D. A., Powell, J., Golde, T. E., Graff, C., De Jager, P. L., Morgan, K., Ertekin-Taner, N., Combarros, O., Psaty, B. M., Passmore, P., Younkin, S. G., Berr, C., Gudnason, V., Rujescu, D., Dickson, D. W., Dartigues, J. F., Destefano, A. L., Ortega-Cubero, S., Hakonarson, H., Campion, D., Boada, M., Kauwe, J. K., Farrer, L. A., Van Broeckhoven, C., Ikram, M. A., Jones, L., Haines, J. L., Tzourio, C., Launer, L. J., Escott-Price, V., Mayeux, R., Deleuze, J. F., Amin, N., Holmans, P. A., Pericak-Vance, M. A., Amouyel, P., van Duijn, C. M., Ramirez, A., Wang, L. S., Lambert, J. C., Seshadri, S., Williams, J., Schellenberg, G. D., Destefano, Anita L., Seshardi, Sudha, Winslow, A. R., Masullo, C. (ORCID:0000-0001-7798-3410), Spalletta, G., Daniele, A. (ORCID:0000-0003-1641-5852), Peloso, Gina M., van der Lee, Sven J., Sims, R., van der Lee, S. J., Naj, A. C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B. W., Boland, A., Raybould, R., Bis, J. C., Martin, E. R., Grenier-Boley, B., Heilmann-Heimbach, S., Chouraki, V., Kuzma, A. B., Sleegers, K., Vronskaya, M., Ruiz, A., Graham, R. R., Olaso, R., Hoffmann, P., Grove, M. L., Vardarajan, B. N., Hiltunen, M., Nöthen, M. M., White, C. C., Hamilton-Nelson, K. L., Epelbaum, J., Maier, W., Choi, S. H., Beecham, G. W., Dulary, C., Herms, S., Smith, A. V., Funk, C. C., Derbois, Null, Forstner, A. J., Ahmad, S., Li, H., Bacq, D., Harold, D., Satizabal, C. L., Valladares, O., Squassina, A., Thomas, R., Brody, J. A., Qu, L., Sánchez-Juan, P., Morgan, T., Wolters, F. J., Zhao, Yu Yang, Garcia, F. S., Denning, N., Fornage, M., Malamon, J., Naranjo, M. C. D., Majounie, E., Mosley, T. H., Dombroski, B., Wallon, D., Lupton, M. K., Dupuis, J., Whitehead, P., Fratiglioni, L., Medway, C., Jian, X., Mukherjee, S., Keller, L., Brown, K., Lin, H., Cantwell, L. B., Panza, F., Mcguinness, B., Moreno-Grau, S., Burgess, J. D., Solfrizzi, V., Proitsi, P., Adams, H. H., Allen, M., Seripa, D., Pastor, P., Cupples, L. A., Price, N. D., Hannequin, D., Frank-García, A., Levy, D., Chakrabarty, P., Caffarra, P., Giegling, I., Beiser, A. S., Giedraitis, V., Hampel, H., Garcia, M. E., Wang, X., Lannfelt, L., Mecocci, P., Eiriksdottir, G., Crane, P. K., Pasquier, F., Boccardi, V., Henández, I., Barber, R. C., Scherer, M., Tarraga, L., Adams, P. M., Leber, M., Chen, Y., Albert, M. S., Riedel-Heller, S., Emilsson, V., Beekly, D., Braae, A., Schmidt, R., Blacker, D., Masullo, Carlo, Schmidt, H., Doody, R. S., Spalletta, Gianfranco, Longstreth, W. T., Fairchild, T. J., Bossù, P., Lopez, O. L., Frosch, M. P., Sacchinelli, E., Ghetti, B., Yang, Q., Huebinger, R. M., Jessen, F., Li, S., Kamboh, M. I., Morris, J., Sotolongo-Grau, O., Katz, M. J., Corcoran, C., Dunstan, M., Braddel, A., Thomas, C., Meggy, A., Marshall, R., Gerrish, A., Chapman, J., Aguilar, M., Taylor, S., Hill, M., Fairén, M. D., Hodges, A., Vellas, B., Soininen, H., Kloszewska, I., Daniilidou, M., Uphill, J., Patel, Y., Hughes, J. T., Lord, J., Turton, J., Hartmann, A. M., Cecchetti, R., Fenoglio Gaddo, Maria Cristina, Serpente, M., Arcaro, M., Caltagirone, C., Orfei, M. D., Ciaramella, A., Pichler, S., Mayhaus, M., Gu, W., Lleó, A., Fortea, J., Blesa, R., Barber, I. S., Brookes, K., Cupidi, C., Maletta, R. G., Carrell, D., Sorbi, S., Moebus, S., Urbano, M., Pilotto, A., Kornhuber, J., Bosco, P., Todd, S., Craig, D., Johnston, J., Gill, M., Lawlor, B., Lynch, A., Fox, N. C., Hardy, J., Albin, R. L., Apostolova, L. G., Arnold, S. E., Asthana, S., Atwood, C. S., Baldwin, C. T., Barnes, L. L., Barral, S., Beach, T. G., Becker, J. T., Bigio, E. H., Bird, T. D., Boeve, B. F., Bowen, J. D., Boxer, A., Burke, J. R., Burns, J. M., Buxbaum, J. D., Cairns, N. J., Cao, C., Carlson, C. S., Carlsson, C. M., Carney, R. M., Carrasquillo, M. M., Carroll, S. L., Diaz, C. C., Chui, H. C., Clark, D. G., Cribbs, D. H., Crocco, E. A., Decarli, C., Dick, M., Duara, R., Evans, D. A., Faber, K. M., Fallon, K. B., Fardo, D. W., Farlow, M. R., Ferris, S., Foroud, T. M., Galasko, D. R., Gearing, M., Geschwind, D. H., Gilbert, J. R., Graff-Radford, N. R., Green, R. C., Growdon, J. H., Hamilton, R. L., Harrell, L. E., Honig, L. S., Huentelman, M. J., Hulette, C. M., Hyman, B. T., Jarvik, G. P., Abner, E., Jin, L. W., Jun, G., Karydas, A., Kaye, J. A., Kim, R., Kowall, N. W., Kramer, J. H., Laferla, F. M., Lah, J. J., Leverenz, J. B., Levey, A. I., Li Quadri Cassini, Giancarlo, Lieberman, A. P., Lunetta, K. L., Lyketsos, C. G., Marson, D. C., Martiniuk, F., Mash, D. C., Masliah, E., Mccormick, W. C., Mccurry, S. M., Mcdavid, A. N., Mckee, A. C., Mesulam, M., Miller, B. L., Miller, C. A., Miller, J. W., Morris, J. C., Murrell, J. R., Myers, A. J., O'Bryant, S., Olichney, J. M., Pankratz, V. S., Parisi, J. E., Paulson, H. L., Perry, W., Peskind, E., Pierce, A., Poon, W. W., Potter, H., Quinn, J. F., Raj, A., Raskind, M., Reisberg, B., Reitz, C., Ringman, J. M., Roberson, E. D., Rogaeva, E., Rosen, H. J., Rosenberg, R. N., Sager, M. A., Saykin, A. J., Schneider, J. A., Schneider, L. S., Seeley, W. W., Smith, A. G., Sonnen, J. A., Spina, S., Stern, R. A., Swerdlow, R. H., Tanzi, R. E., Thornton-Wells, T. A., Trojanowski, J. Q., Troncoso, J. C., Van Deerlin, V. M., Van Eldik, L. J., Vinters, H. V., Vonsattel, J. P., Weintraub, S., Welsh-Bohmer, K. A., Wilhelmsen, K. C., Williamson, J., Wingo, T. S., Woltjer, R. L., Wright, C. B., Yu, C. E., Yu, L., Garzia, F., Golamaully, F., Septier, G., Engelborghs, S., Vandenberghe, R., De Deyn, P. P., Fernadez, C. M., Benito, Y. A., Thonberg, H., Forsell, C., Lilius, L., Kinhult-Stählbom, A., Kilander, L., Brundin, R., Concari, L., Helisalmi, S., Koivisto, A. M., Haapasalo, A., Dermecourt, V., Fievet, N., Hanon, O., Dufouil, C., Brice, A., Ritchie, K., Dubois, B., Himali, J. J., Keene, C. D., Tschanz, J., Fitzpatrick, A. L., Kukull, W. A., Norton, M., Aspelund, T., Larson, E. B., Munger, R., Rotter, J. I., Lipton, R. B., Bullido, M. J., Hofman, A., Montine, T. J., Coto, E., Boerwinkle, E., Petersen, R. C., Alvarez, V., Rivadeneira, F., Reiman, E. M., Gallo, Massimiliano, O'Donnell, C. J., Reisch, J. S., Bruni, A. C., Royall, D. R., Dichgans, M., Sano, M., Galimberti, D., St George-Hyslop, P., Scarpini, E., Tsuang, D. W., Mancuso, M., Bonuccelli, U., Daniele, Antonio, Wu, C. K., Peters, O., Nacmias, B., Riemenschneider, M., Heun, R., Brayne, C., Rubinsztein, D. C., Bras, J., Guerreiro, R., Al-Chalabi, A., Shaw, C. E., Collinge, J., Mann, D., Tsolaki, M., Clarimón, J., Sussams, R., Lovestone, S., O'Donovan, M. C., Owen, M. J., Behrens, T. W., Mead, S., Goate, A. M., Uitterlinden, A. G., Holmes, C., Cruchaga, C., Ingelsson, M., Bennett, D. A., Powell, J., Golde, T. E., Graff, C., De Jager, P. L., Morgan, K., Ertekin-Taner, N., Combarros, O., Psaty, B. M., Passmore, P., Younkin, S. G., Berr, C., Gudnason, V., Rujescu, D., Dickson, D. W., Dartigues, J. F., Destefano, A. L., Ortega-Cubero, S., Hakonarson, H., Campion, D., Boada, M., Kauwe, J. K., Farrer, L. A., Van Broeckhoven, C., Ikram, M. A., Jones, L., Haines, J. L., Tzourio, C., Launer, L. J., Escott-Price, V., Mayeux, R., Deleuze, J. F., Amin, N., Holmans, P. A., Pericak-Vance, M. A., Amouyel, P., van Duijn, C. M., Ramirez, A., Wang, L. S., Lambert, J. C., Seshadri, S., Williams, J., Schellenberg, G. D., Destefano, Anita L., Seshardi, Sudha, Winslow, A. R., Masullo, C. (ORCID:0000-0001-7798-3410), Spalletta, G., and Daniele, A. (ORCID:0000-0003-1641-5852)
Abstract: Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C. Methods: Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger. Results: Based on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P >.7). Discussion: Our study does not support the role of HDL-C on risk of AD through HDL-C altered by CETP. This study does not rule out other mechanisms by which HDL-C affects risk of AD.
Published: 2018

25. Cooperative resorts: An analysis of creative integration strategies in community destinations

Author: Volgger, Michael, Herntrei, M., Pechlaner, H., Pichler, S., Volgger, Michael, Herntrei, M., Pechlaner, H., and Pichler, S.
Abstract: Hotel resorts may be understood as stand-alone, large-scale tourist operations. Hotel resort development provides a sometimes criticised but repeatedly followed path towards efficient and effective tourism operations. However, a strong regimentation of quantitative hotel growth complicated such hotel resort development in the region of South Tyrol, Italy, and has prompted some hotel businesses to build alternative strategic alliances. These alliances can be regarded as ‘cooperative resorts’ and characteristically include the integration of spatially divided and legally autonomous hotels within community destinations. The aim of this paper is to explore the nature of these observed cooperative resorts, to trace historical origins and reasons for their appearance and to investigate their impact on broader community destination networks. Based on a series of qualitative interviews, the paper finds that in contrast to enclave-type hotel resort models, cooperative resorts have a reduced tendency to segregate themselves from the respective destination networks, but rather affect their balance of power and impact on destination leadership.
Published: 2018

26. Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies

Author: Broce, Iris, Karch, Celeste M., Wen, Natalie, Fan, Chun C., Wang, Yunpeng, Hong Tan, Chin, Kouri, Naomi, Ross, Owen A., Höglinger, Günter U., Muller, Ulrich, Hardy, John, Momeni, Parastoo, Hess, Christopher P., Dillon, William P., Miller, Zachary A., Bonham, Luke W., Rabinovici, Gil D., Rosen, Howard J., Schellenberg, Gerard D., Franke, Andre, Karlsen, Tom H., Veldink, Jan H., Ferrari, Raffaele, Yokoyama, Jennifer S., Miller, Bruce L., Andreassen, Ole A., Dale, Anders M., Desikan, Rahul S., Sugrue, Leo P., Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JBJ, Dobson-Stone C, Brooks WS, Schofield PR, Halliday GM, Hodges JR, Piguet O, Bartley L, Thompson E, Haan E, Hernández I, Ruiz A, Boada M, Borroni B, Padovani A, Cruchaga C, Cairns NJ, Benussi L, Binetti G, Ghidoni R, Forloni G, Galimberti D, Fenoglio C, Serpente M, Scarpini E, Clarimón J, Lleó A, Blesa R, Waldö ML, Nilsson K, Nilsson C, Mackenzie IRA, Hsuing GYR, Mann DMA, Grafman J, Morris CM, Attems J, Griffiths TD, McKeith IG, Thomas AJ, Pietrini P, Huey ED, Wasserman EM, Baborie A, Jaros E, Tierney MC, Pastor P, Razquin C, Ortega-Cubero S, Alonso E, Perneczky E, Diehl-Schmid J, Alexopoulos P, Kurz A, Rainero I, Rubino E, Pinessi L, Rogaeva E, St George-Hyslop P, Rossi G, Tagliavini F, Giaccone G, Rowe JB, Schlachetzki JCM, Uphill J, Collinge J, Mead S, Danek A, Van Deerlin VM, Grossmann M, Trojanowski JQ, van der Zee J, Deschamps W, Van Langenhove T, Cruts M, Van Broeckhoven C, Cappa SF, Le Ber I, Hannequin D, Golfier V, Vercelletto M, Brice A, Nacmias B, Sorbi S, Bagnoli S, Piaceri I, Nielsen JE, Hjermind LE, Riemenschneider M, Mayhaus M, Ibach B, Gasparoni G, Pichler S, Gu W, Rossor MN, Fox NC, Warren JD, Spillantini MG, Morris HR, Rizzu P, Heutnik P, Snowden J, Rollinson S, Richardson A, Gerhard A, Bruni AC, Maletta R, Frangipane F, Cupidi C, Bernardi L, Anfossi M, Gallo M, Conidi ME, Smirne N, Rademakers R, Baker M, Dickson DW, Graff-Radford NR, Peterson RC, Knopman D, Josephs KA, Boeve BF, Parisi JE, Seeley WW, Miller BL, Karydas AM, Rosen H, van Swieten JC, Dopper EGP, Seelaar H, Pijnenburg YAL, Scheltens P, Logroscino G, Capozzo R, Novelli V, Puca AA, Franceschi M, Postiglione A, Milan G, Sorrentino P, Kristiansen M, Chiang HH, Graff C, Pasquier F, Rollin A, Deramecourt V, Lebert F, Kapogiannis D, Ferucci L, Pickering-Brown S, Singleton AB, Hardy J, Momeni P., Broce, Iris [0000-0003-4932-1430], Karch, Celeste M [0000-0002-6854-5547], Wang, Yunpeng [0000-0001-9831-1090], Tan, Chin Hong [0000-0002-0980-9936], Kouri, Naomi [0000-0002-6841-9882], Hess, Christopher P [0000-0002-5132-5302], Miller, Zachary A [0000-0002-5991-3053], Bonham, Luke W [0000-0002-2533-1266], Veldink, Jan H [0000-0001-5572-9657], Dale, Anders M [0000-0002-6126-2966], Desikan, Rahul S [0000-0002-4151-6017], Sugrue, Leo P [0000-0001-7315-4519], Apollo - University of Cambridge Repository, Neurology, Human genetics, Amsterdam Neuroscience - Neurodegeneration, Divisions, Rademakers, Rosa, Int FTD-Genomics Consortium, Broce, Iri, Karch, Celeste M., Wen, Natalie, Fan, Chun C., Wang, Yunpeng, Hong Tan, Chin, Kouri, Naomi, Ross, Owen A., Höglinger, Günter U., Muller, Ulrich, Hardy, John, Momeni, Parastoo, Hess, Christopher P., Dillon, William P., Miller, Zachary A., Bonham, Luke W., Rabinovici, Gil D., Rosen, Howard J., Schellenberg, Gerard D., Franke, Andre, Karlsen, Tom H., Veldink, Jan H., Ferrari, Raffaele, Yokoyama, Jennifer S., Miller, Bruce L., Andreassen, Ole A., Dale, Anders M., Desikan, Rahul S., Sugrue, Leo P., Ferrari, R, Hernandez, Dg, Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jbj, Dobson-Stone, C, Brooks, W, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, Ml, Nilsson, K, Nilsson, C, Mackenzie, Ira, Hsuing, Gyr, Mann, Dma, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wasserman, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, E, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jcm, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, Vm, Grossmann, M, Trojanowski, Jq, van der Zee, J, Deschamps, W, Van Langenhove, T, Cruts, M, Van Broeckhoven, C, Cappa, Sf, Le Ber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Spillantini, Mg, Morris, Hr, Rizzu, P, Heutnik, P, Snowden, J, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, Me, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff-Radford, Nr, Peterson, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Miller, Bl, Karydas, Am, Rosen, H, van Swieten, Jc, Dopper, Egp, Seelaar, H, Pijnenburg, Yal, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebert, F, Kapogiannis, D, Ferucci, L, Pickering-Brown, S, Singleton, Ab, Hardy, J, and Momeni, P.
Subjects: 0301 basic medicine, Linkage disequilibrium, Gene Expression, Genome-wide association study, Neurodegenerative, Medical and Health Sciences, Motor Neuron Diseases, 0302 clinical medicine, Medicine and Health Sciences, 2.1 Biological and endogenous factors, Corticobasal degeneration, genetics [Genetic Predisposition to Disease], genetics [Frontotemporal Dementia], Genetics, Medicine (all), Neurodegenerative Diseases, Single Nucleotide, Genomics, General Medicine, Middle Aged, Colitis, LRRK2, 3. Good health, Neurology, Manchester Institute for Collaborative Research on Ageing, Frontotemporal Dementia, Neurological, Medicine, Research Article, Frontotemporal dementia, ResearchInstitutes_Networks_Beacons/MICRA, Immunology, Rheumatoid Arthritis, Single-nucleotide polymorphism, Gastroenterology and Hepatology, Human leukocyte antigen, Biology, Autoimmune Disease, Polymorphism, Single Nucleotide, Autoimmune Diseases, 03 medical and health sciences, Rare Diseases, Rheumatology, Clinical Research, General & Internal Medicine, FTD GWA, Mental Health and Psychiatry, mental disorders, Acquired Cognitive Impairment, Genome-Wide Association Studies, medicine, Ulcerative Colitis, Humans, Inflammatory and Immune System, Genetic Predisposition to Disease, ddc:610, Polymorphism, Aged, Genetic association, Genome-Wide Association Study, International FTD-Genomics Consortium, Prevention, Arthritis, Human Genome, Inflammatory Bowel Disease, Amyotrophic Lateral Sclerosis, Neurosciences, Correction, Biology and Life Sciences, Computational Biology, nutritional and metabolic diseases, Human Genetics, Genome Analysis, medicine.disease, Brain Disorders, nervous system diseases, 030104 developmental biology, Genetic Loci, Genetics of Disease, Dementia, Clinical Immunology, Human medicine, Clinical Medicine, Digestive Diseases, 030217 neurology & neurosurgery
Abstract: Background Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. Methods and findings Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders—namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)—and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate < 0.05 and after excluding SNPs in linkage disequilibrium, we found that 8 of the 15 identified loci mapped to the human leukocyte antigen (HLA) region on Chromosome (Chr) 6. We also found novel candidate FTD susceptibility loci within LRRK2 (leucine rich repeat kinase 2), TBKBP1 (TBK1 binding protein 1), and PGBD5 (piggyBac transposable element derived 5). Functionally, we found that the expression of FTD–immune pleiotropic genes (particularly within the HLA region) is altered in postmortem brain tissue from patients with FTD and is enriched in microglia/macrophages compared to other central nervous system cell types. The main study limitation is that the results represent only clinically diagnosed individuals. Also, given the complex interconnectedness of the HLA region, we were not able to define the specific gene or genes on Chr 6 responsible for our pleiotropic signal. Conclusions We show immune-mediated genetic enrichment specifically in FTD, particularly within the HLA region. Our genetic results suggest that for a subset of patients, immune dysfunction may contribute to FTD risk. These findings have potential implications for clinical trials targeting immune dysfunction in patients with FTD., Rahul Desikan and colleagues use summary data from genome-wide association studies to investigate genetic overlap between frontotemporal dementia and a several immune-mediated diseases, and identify microglia and inflammation-associated genes that may play a role in FTD pathogenesis., Author summary Why was this study done? Frontotemporal dementia (FTD) is the leading cause of dementia in individuals less than 65 years old. Currently, there is no approved treatment of FTD and no diagnostic tests for predicting disease onset or measuring progression. Increasing evidence suggests that inflammation and immune system dysfunction play an important role in the pathogenesis of FTD. What did the researchers do and find? We used summary data from genome-wide association studies to investigate genetic overlap, or “pleiotropy,” between FTD and a variety of immune-mediated diseases. Through this approach, we found extensive FTD–immune genetic overlap within the HLA region on Chromosome 6, an area rich in genes related to microglial function, as well as in 3 genes not previously identified as contributing to the pathophysiology of FTD. Pointing to the functional relevance of these genetic results, we found that these candidate FTD–immune genes are differentially expressed in postmortem brains from patients with FTD compared to controls, and in microglia/macrophages compared with other central nervous system cells. Using bioinformatics tools, we explored protein and genetic interactions among our candidate FTD–immune genes. These results suggest that rather than a few individual loci, large portions of the HLA region may be associated with increased FTD risk. What do these findings mean? Immune dysfunction may play a role in the pathophysiology of a subset of FTD cases. For a subset of patients in whom immune dysfunction in general—and microglial activation in particular—is central to disease pathophysiology, anti-inflammatory treatment is an important area for further investigation.
Published: 2018

27. A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease

Author: Hartl, D, May, P, Gu, W, Mayhaus, M, Pichler, S, Spaniol, C, Glaab, E, Bobbili, DR, Antony, P, Koegelsberger, S, Kurz, A, Grimmer, T, Morgan, K, Vardarajan, BN, Reitz, C, Hardy, J, Bras, J, Guerreiro, R, Balling, R, Schneider, JG, Riemenschneider, M, Sassi, C, Gibbs, JR, Hernandez, D, Brookes, KJ, Guetta-Baranes, T, Francis, PT, Lupton, MK, Brown, K, Powell, J, and Singleton, A
Subjects: 0301 basic medicine, Nonsynonymous substitution, Male, Molecular biology, Genome-wide association study, Biology, ADAM17 Protein, Article, Transcriptome, Pathogenesis, 03 medical and health sciences, Cellular and Molecular Neuroscience, Amyloid beta-Protein Precursor, 0302 clinical medicine, Alzheimer Disease, Loss of Function Mutation, Germany, Exome Sequencing, Genetics, Humans, Genetic Predisposition to Disease, Gene, Genotyping, Loss function, Genetic association, Aged, Middle Aged, 3. Good health, ddc, Psychiatry and Mental health, 030104 developmental biology, Case-Control Studies, Mutation, Female, Amyloid Precursor Protein Secretases, 030217 neurology & neurosurgery, Genome-Wide Association Study, Neuroscience
Abstract: Common variants of about 20 genes contributing to AD risk have so far been identified through genome-wide association studies (GWAS). However, there is still a large proportion of heritability that might be explained by rare but functionally important variants. One of the so far identified genes with rare AD causing variants is ADAM10. Using whole-genome sequencing we now identified a single rare nonsynonymous variant (SNV) rs142946965 [p.R215I] in ADAM17 co-segregating with an autosomal-dominant pattern of late-onset AD in one family. Subsequent genotyping and analysis of available whole-exome sequencing data of additional case/control samples from Germany, UK, and USA identified five variant carriers among AD patients only. The mutation inhibits pro-protein cleavage and the formation of the active enzyme, thus leading to loss-of-function of ADAM17 alpha-secretase. Further, we identified a strong negative correlation between ADAM17 and APP gene expression in human brain and present in vitro evidence that ADAM17 negatively controls the expression of APP. As a consequence, p.R215I mutation of ADAM17 leads to elevated Aß formation in vitro. Together our data supports a causative association of the identified ADAM17 variant in the pathogenesis of AD.
Published: 2017

28. Susceptible genes and disease mechanisms identified in frontotemporal dementia and frontotemporal dementia with Amyotrophic Lateral Sclerosis by DNA-methylation and GWAS

Author: Taskesen, E, Mishra, A, van der Sluis, S, Ferrari, R, Veldink, Jh, van Es MA4, Smit, Ab5, Posthuma, D1, 2, Hernandez DG, Pijnenburg Y., Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jbj, Dobson-Stone, C, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, Roberta, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, Ml, Nilsson, K, Nilsson, C, Mackenzie, Ira, Hsiung, Gr, Mann, Dma, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wassermann, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, George-Hyslop, Ps, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jcm, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin VM, Grossman, M, Trojanowski, Jq, van der Zee, J, Van Broeckhoven, C, Cappa, Sf, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, GUNNAR MARKUS, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Spillantini, Mg, Morris, Hr, Rizzu, P, Heutink, P, Snowden, Js, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, Lara, Anfossi, M, Gallo, M, Conidi, Me, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff-Radford, Nr, Petersen, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Miller, Bl, Karydas, Am, Rosen, H, van Swieten JC, Dopper, Egp, Seelaar, H, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, Antonio, Milan, Gian Luca, Sorrentino, Paolo Luigi, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, Ab, Hardy, J, Momeni, P., Rademakers, Rosa, International FTD-Genomics Consortium, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, APH - Quality of Care, Midwifery Science, Divisions, Neurology, Amsterdam Reproduction & Development (AR&D), Mishra, A [0000-0002-8141-1543], van der Sluis, S [0000-0001-9958-7216], van Es, MA [0000-0002-7709-5883], Posthuma, D [0000-0001-7582-2365], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Candidate gene, Science, Genome-wide association study, Biology, Neurodegenerative, Article, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, SDG 3 - Good Health and Well-being, mental disorders, medicine, Journal Article, Acquired Cognitive Impairment, Genetics, 2.1 Biological and endogenous factors, Amyotrophic lateral sclerosis, Aetiology, General, Alzheimer's Disease Related Dementias (ADRD), Genetic association, Multidisciplinary, Genetic heterogeneity, International FTD-Genomics Consortium, Neurodegeneration, Human Genome, Neurosciences, nutritional and metabolic diseases, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, nervous system diseases, Brain Disorders, Frontotemporal Dementia (FTD), 030104 developmental biology, DNA methylation, Neurological, Medicine, Dementia, Human medicine, ALS, 030217 neurology & neurosurgery, Frontotemporal dementia
Abstract: Frontotemporal dementia (FTD) is a neurodegenerative disorder predominantly affecting the frontal and temporal lobes. Genome-wide association studies (GWAS) on FTD identified only a few risk loci. One of the possible explanations is that FTD is clinically, pathologically, and genetically heterogeneous. An important open question is to what extent epigenetic factors contribute to FTD and whether these factors vary between FTD clinical subgroup. We compared the DNA-methylation levels of FTD cases (n = 128), and of FTD cases with Amyotrophic Lateral Sclerosis (FTD-ALS; n = 7) to those of unaffected controls (n = 193), which resulted in 14 and 224 candidate genes, respectively. Cluster analysis revealed significant class separation of FTD-ALS from controls. We could further specify genes with increased susceptibility for abnormal gene-transcript behavior by jointly analyzing DNA-methylation levels with the presence of mutations in a GWAS FTD-cohort. For FTD-ALS, this resulted in 9 potential candidate genes, whereas for FTD we detected 1 candidate gene (ELP2). Independent validation-sets confirmed the genes DLG1, METTL7A, KIAA1147, IGHMBP2, PCNX, UBTD2, WDR35, and ELP2/SLC39A6 among others. We could furthermore demonstrate that genes harboring mutations and/or displaying differential DNA-methylation, are involved in common pathways, and may therefore be critical for neurodegeneration in both FTD and FTD-ALS.
Published: 2017

29. Immune-related genetic enrichment in frontotemporal dementia

Author: Broce, Iris, Karch, Celeste M., Wen, Natalie, Fan, Chun C., Wang, Yunpeng, Hong Tan, Chin, Kouri, Naomi, Ross, Owen A., Höglinger, Günter U., Muller, Ulrich, Hardy, John, Momeni, Parastoo, Hess, Christopher P., Dillon, William P., Miller, Zachary A., Bonham, Luke W., Rabinovici, Gil D., Rosen, Howard J., Schellenberg, Gerard D., Franke, Andre, Karlsen, Tom H., Veldink, Jan H., Ferrari, Raffaele, Yokoyama, Jennifer S., Miller, Bruce L., Andreassen, Ole A., Dale, Anders M., Desikan, Rahul S., Sugrue, Leo P., Ferrari, R, Hernandez, D G, Nalls, M A, Rohrer, J D, Ramasamy, A, Kwok, J B J, Dobson-Stone, C, Schofield, P R, Halliday, G M, Hodges, J R, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, N J, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Landqvist Waldö, M, Nilsson, K, Nilsson, C, Mackenzie, I R A, Hsiung, G-Y R, Mann, D M A, Grafman, J, Morris, C M, Attems, J, Griffiths, T D, McKeith, I G, Thomas, A J, Pietrini, P, Huey, E D, Wassermann, E M, Baborie, A, Jaros, E, Tierney, M C, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, George-Hyslop, P St, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, J B, Schlachetzki, J C M, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, V M, Grossman, M, Trojanowski, J Q, der Zee, J van, Cruts, M, Broeckhoven, C Van, Cappa, S F, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, J E, Hjermind, L E, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, M N, Fox, N C, Warren, J D, Spillantini, M G, Morris, H R, Rizzu, P, Heutink, P, Snowden, J S, Rollinson, S, Richardson, A, Gerhard, A, Bruni, A C, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, M E, Smirne, N, Rademakers, R, Baker, M, Dickson, D W, Graff-Radford, N R, Petersen, R C, Knopman, D, Josephs, K A, Boeve, B F, Parisi, J E, Seeley, W W, Miller, B L, Karydas, A M, Rosen, H, van Swieten, J C, Dopper, E G P, Seelaar, H, Pijnenburg, Y A L, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, A A, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, H-H, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, A B, Hardy, J, and Momeni, P
Subjects: Genetics, 0303 health sciences, business.industry, nutritional and metabolic diseases, Single-nucleotide polymorphism, Genome-wide association study, Disease, medicine.disease, nervous system diseases, 3. Good health, Progressive supranuclear palsy, 03 medical and health sciences, 0302 clinical medicine, mental disorders, Immunology, Medicine, Corticobasal degeneration, Amyotrophic lateral sclerosis, business, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association, Frontotemporal dementia
Abstract: BackgroundConverging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed.Methods and findingsUsing large genome-wide association studies (GWAS) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs)jointlyassociated with ‘FTD-related disorders’ namely FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS) – and one or more immune-mediated diseases including Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis (PSOR). We found up to 270-fold genetic enrichment between FTD and RA and comparable enrichment between FTD and UC, T1D, and CeD. In contrast, we found only modest genetic enrichment between any of the immune-mediated diseases and CBD, PSP or ALS. At a conjunction false discovery rate (FDR) < 0.05, we identified numerous FTD-immune pleiotropic SNPs within the human leukocyte antigen (HLA)region on chromosome 6. By leveraging the immune diseases, we also found novel FTD susceptibility loci withinLRRK2(Leucine Rich Repeat Kinase 2), TBKBP1(TANK-binding kinase 1 Binding Protein 1), andPGBD5(PiggyBac Transposable Element Derived 5). Functionally, we found that expression of FTD-immune pleiotropic genes (particularly within theHLAregion) is altered in postmortem brain tissue from patients with frontotemporal dementia and is enriched in microglia compared to other central nervous system (CNS) cell types.ConclusionsWe show considerable immune-mediated genetic enrichment specifically in FTD, particularly within theHLAregion. Our genetic results suggest that for a subset of patients, immune dysfunction may contribute to risk for FTD. These findings have potential implications for clinical trials targeting immune dysfunction in patients with FTD.
Published: 2017

30. Shared genetic risk between corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia

Author: Yokoyama, Jennifer S., Karch, Celeste M., Fan, Chun C., Bonham, Luke W., Naomi, Kouri, Ross, Owen A., Rosa, Rademakers, Jungsu, Kim, Yunpeng, Wang, Höglinger, Günter U., Ulrich, Muller, Raffaele, Ferrari, John, Hardy, International FTD-Genomics Consortium (IFGC Ferrari, R, Hernandez, Dg, Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jbj, Dobson-Stone, C, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Landqvist Waldö, M, Nilsson, C, Mackenzie, Ira, Hsiung, Gyr, Mann, Dma, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wassermann, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jcm, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin VM, Grossman, M, Trojanowski, Jq, van der Zee, J, Cruts, M, Van Broeckhoven, C, Cappa, Sf, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Spillantini, Mg, Morris, Hr, Rizzu, P, Heutink, P, Snowden, Js, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, Me, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff-Radford, Nr, Petersen, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Miller, Bl, Karydas, Am, Rosen, H, van Swieten JC, Dopper, Eg, Seelaar, H, Pijnenburg, Yal, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, Ab, Hardy, J, Momeni, P. )., Parastoo, Momeni, Sugrue, Leo P., Hess, Christopher P., James Barkovich, A., Boxer, Adam L., Seele, William W., Rabinovici, Gil D., Rosen, Howard J., Miller, Bruce L., Schmansky, Nicholas J., Bruce, Fischl, Hyman, Bradley T., Dickson, Dennis W., Schellenberg, Gerard D., Andreassen, Ole A., Dale, Anders M., Desikan, and Rahul S., and Int FTD-Genomics Consortium
Subjects: pathology [Tauopathies], 0301 basic medicine, Pathology, Aging, genetics [Basal Ganglia Diseases], Genome-wide association study, Neurodegenerative, diagnosis [Supranuclear Palsy, Progressive], diagnosis [Frontotemporal Dementia], pathology [Inclusion Bodies], 0302 clinical medicine, Neurology (clinical), Cellular and Molecular Neuroscience, Risk Factors, pathology [Neurons], Corticobasal degeneration, Supranuclear Palsy, 2.1 Biological and endogenous factors, Aetiology, genetics [Frontotemporal Dementia], Alzheimer's Disease Related Dementias (ADRD), Genetics, Inclusion Bodies, Neurons, genetics [Supranuclear Palsy, Progressive], Frontotemporal Dementia (FTD), Tauopathies, Frontotemporal Dementia, Neurological, Supranuclear Palsy, Progressive, Frontotemporal dementia, medicine.medical_specialty, pathology [Supranuclear Palsy, Progressive], Clinical Sciences, MAPT protein, human, Locus (genetics), Single-nucleotide polymorphism, tau Proteins, Biology, Article, Pathology and Forensic Medicine, Progressive supranuclear palsy, 03 medical and health sciences, Rare Diseases, Progressive, Basal Ganglia Diseases, mental disorders, medicine, Acquired Cognitive Impairment, Humans, ddc:610, Genetic association, Neurology & Neurosurgery, International FTD-Genomics Consortium, Prevention, Haplotype, Human Genome, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, metabolism [tau Proteins], digestive system diseases, Brain Disorders, 030104 developmental biology, pathology [Frontotemporal Dementia], Dementia, Human medicine, pathology [Basal Ganglia Diseases], 030217 neurology & neurosurgery
Abstract: Corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and a subset of frontotemporal dementia (FTD) are neurodegenerative disorders characterized by tau inclusions in neurons and glia (tauopathies). Although clinical, pathological and genetic evidence suggests overlapping pathobiology between CBD, PSP, and FTD, the relationship between these disorders is still not well understood. Using summary statistics (odds ratios and p values) from large genome-wide association studies (total n=14,286 cases and controls) and recently established genetic methods, we investigated the genetic overlap between CBD and PSP and CBD and FTD. We found up to 800-fold enrichment of genetic risk in CBD across different levels of significance for PSP or FTD. In addition to NSF (tagging the MAPT H1 haplotype), we observed that SNPs in or near MOBP, CXCR4, EGFR, and GLDC showed significant genetic overlap between CBD and PSP, whereas only SNPs tagging the MAPT haplotype overlapped between CBD and FTD. The risk alleles of the shared SNPs were associated with expression changes in cis-genes. Evaluating transcriptome levels across adult human brains, we found a unique neuroanatomic gene expression signature for each of the five overlapping gene loci (omnibus ANOVA p&nbsp
Published: 2017

31. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases

Author: Wang Y., Ferrari R., Hernandez, D. G, Nalls, M. A, Rohrer, J. D, Ramasamy, A, Kwok, J. B. J, Dobson Stone, C, Schofield, P. R, Halliday, G. M, Hodges, J. R, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, Barbara, Padovani, Alessandro, Cruchaga, C, Cairns, N. J, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Landqvist Waldö, M, Nilsson, K, Nilsson, C, Mackenzie, I. R. A, Hsiung, G. Y. R, Mann, D. M. A, Grafman, J, Morris, C. M, Attems, J, Griffiths, T. D, Mckeith, I. G, Thomas, A. J, Pietrini, P, Huey, E. D, Wassermann, E. M, Baborie, A, Jaros, E, Tierney, M. C, Pastor, P, Razquin, C, Ortega Cubero, S, Alonso, E, Perneczky, R, Diehl Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, J. B, Schlachetzki, J. C. M, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, V. M, Grossman, M, Trojanowski, J. Q, van der Zee, J, Cruts, M, Van Broeckhoven, C, Cappa, S. F, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, J. E, Hjermind, L. E, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, M. N, Fox, N. C, Warren, J. D, Spillantini, M. G, Morris, H. R, Rizzu, P, Heutink, P, Snowden, J. S, Rollinson, S, Richardson, A, Gerhard, A, Bruni, A. C, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, M. E, Smirne, N, Rademakers, R, Baker, M, Dickson, D. W, Graff Radford, N. R, Petersen, R. C, Knopman, D, Josephs, K. A, Boeve, B. F, Parisi, J. E, Seeley, W. W, Miller, B. L, Karydas, A. M, Rosen, H, van Swieten, J. C, Dopper, E. G. P, Seelaar, H, Pijnenburg, Y. A. L, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, A. A, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, H. H, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering Brown, S, Singleton, A. B, Hardy, J, and Momeni, P.
Published: 2017

32. Gene-based association studies report genetic links for clinical subtypes of frontotemporal dementia

Author: Mishra, Aniket, Ferrari, Raffaele, Rohrer, J. D., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Ramasamy, A., Heutink, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Kwok, J. B. J., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Rademakers, R., Baker, M., Dickson, D. W., Graff-Radford, N. R., Petersen, R. C., Knopman, D., Dobson-Stone, C., Josephs, K. A., Boeve, B. F., Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., van Swieten, J. C., Dopper, E. G. P., Seelaar, H., Schofield, P. R., Pijnenburg, Y. A. L., Scheltens, P., Logroscino, G., Capozzo, R., Novelli, V., Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Halliday, G. M., Kristiansen, M., Chiang, H-H, Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Hodges, J. R., Singleton, A. B., Hardy, J., Momeni, P., Piguet, O., Bartley, L., Thompson, E., Heutink, Peter, Haan, E., Hernández, I., Ruiz, A., Boada, M., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Binetti, G., Hardy, John, Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Clarimón, J., Lleó, A., Blesa, R., Pijnenburg, Yolande, Landqvist Waldö, M., Nilsson, K., Nilsson, C., Mackenzie, I. R. A., Hsiung, G-Y R, Mann, D. M. A., Grafman, J., Morris, C. M., Attems, J., Griffiths, T. D., Posthuma, Danielle, McKeith, I. G., Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Pastor, P., Razquin, C., Consortium, International FTD-Genomics, Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., Ferrari, R., St George-Hyslop, P., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C. M., Uphill, J., Collinge, J., Mead, S., Danek, A., Hernandez, D. G., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., van der Zee, J., Cruts, M., Van Broeckhoven, C., Cappa, S. F., Leber, I., Hannequin, D., Golfier, V., Nalls, M. A., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., International FTD-Genomics Consortium, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Human genetics, Neurology, Amsterdam Neuroscience - Neurodegeneration, and Amsterdam Reproduction & Development (AR&D)
Subjects: 0301 basic medicine, Genome-wide association study, 0302 clinical medicine, diagnosis [Frontotemporal Dementia], ARHGAP35 protein, human, Risk Factors, Mitochondrial Precursor Protein Import Complex Proteins, MAGMA, GWAS, Guanine Nucleotide Exchange Factors, genetics [Genetic Predisposition to Disease], genetics [Frontotemporal Dementia], Genetics, genetics [Membrane Transport Proteins], FTD, genetics [Guanine Nucleotide Exchange Factors], TOMM40 protein, human, Frontotemporal Dementia, Allelic heterogeneity, medicine.symptom, Frontotemporal dementia, Semantic dementia, 03 medical and health sciences, Apolipoproteins E, Progressive nonfluent aphasia, stress-signalling pathway, SDG 3 - Good Health and Well-being, gene-based association study, Aphasia, medicine, Genetic predisposition, Journal Article, Humans, Genetic Predisposition to Disease, ddc:610, Alleles, Case-Control Studies, Genetic Association Studies, Membrane Transport Proteins, Protective Factors, Repressor Proteins, alpha 1-Antitrypsin, Neurology (clinical), Biology, Genetic association, business.industry, SERPINA1 protein, human, medicine.disease, genetics [alpha 1-Antitrypsin], genetics [Repressor Proteins], 030104 developmental biology, genetics [Apolipoproteins E], Human medicine, business, Neuroscience, 030217 neurology & neurosurgery, Meta-Analysis
Abstract: Genome-wide association studies in frontotemporal dementia showed limited success in identifying associated loci. This is possibly due to small sample size, allelic heterogeneity, small effect sizes of single genetic variants, and the necessity to statistically correct for testing millions of genetic variants. To overcome these issues, we performed gene-based association studies on 3348 clinically identified frontotemporal dementia cases and 9390 controls (discovery, replication and joint-cohort analyses). We report association of APOE and TOMM40 with behavioural variant frontotemporal dementia, and ARHGAP35 and SERPINA1 with progressive non-fluent aphasia. Further, we found the ɛ2 and ɛ4 alleles of APOE harbouring protective and risk increasing effects, respectively, in clinical subtypes of frontotemporal dementia against neurologically normal controls. The APOE-locus association with behavioural variant frontotemporal dementia indicates its potential risk-increasing role across different neurodegenerative diseases, whereas the novel genetic associations of ARHGAP35 and SERPINA1 with progressive non-fluent aphasia point towards a potential role of the stress-signalling pathway in its pathophysiology.
Published: 2017

33. The glass ceiling in human resources: exploring the link between women's representation in management and the practices of strategic human resource management and employee involvement.

Author: Pichler S, Simpson PA, and Stroh LK
Abstract: Research on sex stereotypes suggests that gender bias is an invisible barrier-the so-called glass ceiling-preventing women from breaking into the highest levels of management in business organizations. Using data from a state-based professional HR organization, we investigated this phenomenon in the field of HR management. Building on the lack of fit model of gender discrimination and previous research, we tested two hypotheses: that women in HR are more likely to be concentrated in lower-level managerial positions in organizations that emphasize employee involvement (because of a related emphasis on stereotypically feminine managerial abilities) and that women in HR also are more likely to be concentrated in lower-level managerial positions in organizations that emphasize strategic human resource management (because of a related emphasis on stereotypically masculine characteristics). Our results support the first but not the second hypothesis. Theoretical and practical implications related to the glass ceiling are discussed. © 2008 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
Published: 2008
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34. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Author: Lambert, J. C., Ibrahim-Verbaas, C. A., Russo, G., Mayhaus, M., Lannefelt, L., Hakonarson, H., Pichler, S., Carrasquillo, M. M., Ingelsson, M., Beekly, D., Alvarez, V., Zou, F., Valladares, O., Thorton-Wells, T. A., Younkin, S. G., Coto, E., Hamilton-Nelson, K. L., Gu, W., Razquin, C., Pastor, P., Mateo, I., Owen, M. J., Faber, K. M., Jonsson, P. V., Jones, N., Combarros, O., O'Donovan, M. C., Cantwell, L. B., Soininen, H., Blacker, D., Mead, S., Mosley, T. H., Bennett, D. A., Harris, T. B., Fratiglioni, L., Smith, A. V., Holmes, C., de Bruijn, R. F., Passmore, P., Montine, T. J., Bettens, K., Rotter, J. I., Brice, A., Morgan, K., Foroud, T. M., Kukull, W. A., Chouraki, V., Hannequin, D., Powell, J. F., Nalls, M. A., Ritchie, K., Lunetta, K. L., Kauwe, J. S., Boerwinkle, E., Riemenschneider, M., Boada, M., Hiltuenen, M., Thomas, C., Martin, E. R., Schmidt, R., Rujescu, D., Wang, L. S., Dartigues, J. F., Mayeux, R., Tzourio, C., Hofman, A., Nöthen, M. M., Graff, C., Ikram, M. A., Psaty, B. M., Jones, L., Haines, J. L., Holmans, P. A., Lathrop, M., Pericak-Vance, M. A., Launer, L. J., Farrer, L. A., van Duijn, C. M., Van Broeckhoven, C., Zelenika, D., Moskvina, V., Seshadri, S., Williams, J., Schellenberg, G. D., Amouyel, P., Alpérovitch, A., Boland, A., Delépoine, M., Dubois, B., Duron, E., Vardarajan, B. N., Epelbaum, J., Van Cauwenberghe, C., Engelborghs, S., Vandenberghe, R., De Deyn, P. P., Ferri, R., Romano, C., Caltagirone, C., Orfei, M. D., Ciaramella, A., Kamatani, Y., Scarpini, E., Fenoglio, C., Siciliano, G., Bonuccelli, U., Bagnoli, S., Bracco, L., Bessi, V., Cecchetti, R., Bastgiani, P., Squassina, A., Harold, D., Lin, C. F., Seripa, D., Frank-García, A., Sastre, I., Blesa, R., Alcolea, D., Suárez-Clavet, M., Sánchez-Juan, P., Muñoz Fernandez, C., Aladro Benito, Y., Thonberg, H., Gerrish, A., Forshell, C., Lilus, L., Kinhult-Ståhlbom, A., Giedraitis, V., Kilander, L., Brundin, R. M., Concari, L., Helisalmi, S., Koivisto, A. M., Haapasalo, A., Schmidt, H., Solfrizzi, V., Frisardi, V., Ott, J., Carney, R. M., Mash, D. C., Albert, M. S., Albin, R. L., Apostolova, L. G., Arnold, S. E., Barmada, M. M., Kunkle, B., Barnes, L. L., Beach, T. G., Bigio, E. H., Bird, T. D., Boeve, B. F., Bowen, J. D., Boxer, A., Burk, J. R., Cairns, N. J., Cao, C., Dunstan, M. L., Carlson, C. S., Carroll, S. L., Chibnik, L. B., Chui, H. C., Clark, D. G., Corneveaux, J., Cribbs, D. G., DeCarli, C., DeKosky, S. T., Demirci, F. Y., Ruiz, A., Dick, M., Dickson, D. W., Duara, R., Ertekin-Taner, N., Fallon, K. B., Farlow, M. R., Ferris, S., Frosch, M. P., Galasko, G. R., Ganguli, M., Bihoreau, M. T., Gearing, M., Geschwind, D. H., Ghetti, B., Gilman, S., Glass, J. D., Growdon, J. H., Hamilton, R. L., Harrell, L. E., Head, E., Honig, L. S., Choi, S. H., Hulette, C. M., Hyman, B. T., Jarvik, G. P., Jicha, G. A., Jin, L. W., Karydas, A., Kaye, J. A., Kim, R., Koo, E. H., Reitz, C., Kowall, N. W., Kramer, J. H., Kramer, P., LaFerla, F. M., Lah, J. J., Levernez, J. B., Levey, A. I., Li, G., Lieberman, A. P., Lyketsos, C. G., Pasquier, F., Mack, W. J., Marson, D. C., Martiniuk, F., Masliah, E., McCormick, W. C., McCurry, S. M., McDavid, A. N., McKee, A. C., Mesulam, M., Miller, B. L., Naj, A. C., Cruchaga, C., Miller, C. A., Miller, J. W., Morris, J. C., Murrell, J. R., Olichney, J. M., Pankratz, V. S., Parasi, J. E., Peskind, E., Peterson, R. C., Pierce, A., Craig, D., Poon, W. W., Potter, H., Quinn, J. F., Raj, A., Raskind, M., Raiman, E. M., Reisberg, B., Ringman, J. M., Roberson, E. D., Rosen, H. J., Amin, N., Rosenberg, R. N., Sano, M., Saykin, A. J., Schneider, J. A., Schneider, L. S., Seely, W. W., Smith, A. G., Sonnen, J. A., Spina, S., Stern, R. A., Berr, C., Tanzi, R. E., Trojanowski, J. Q., Troncoso, J. C., Van Deerlin, V. M., Van Eldik, L. J., Vinters, H. V., Vonsattel, J. P., Weintraub, S., Welsh-Bohmer, K. A., Williamson, J., Lopez, O. L., Woltjer, R. L., Yu, C. E., Barber, R., Au, R., Wolf, P. A., Beiser, A., Debette, S., Yang, Q., Weinstein, G., Johnson, A. D., De Jager, P. L., Wang, J., Uitterlinden, A. G., Rivadeneira, F., Koudstgaal, P. J., Longstreth, W. T., Becker, J. T., Kuller, L. H., Lumley, T., Rice, K., Garcia, M., Deramecourt, V., Aspelund, T., Marksteiner, J. J., Dal-Bianco, P., Töglhofer, A. M., Freudenberger, P., Ransmayr, G., Benke, T., Toeglhofer, A. M., Bressler, J., Breteler, M. M., Johnston, J. A., Fornage, M., Hernández, I., Rosende Roca, M., Ana Mauleón, M., Alegrat, M., RamÍrez-Lorca, R., González-Perez, A., Chapman, J., Stretton, A., Morgan, A., Evans, D., Kehoe, P. G., Medway, C., Lord, J., Turton, J., Hooper, N. M., Vardy, E., Warren, J. D., Schott, J. M., Uphill, J., Ryan, N., Lovestone, S., Rossor, M., Ben-Shlomo, Y., Makrina, D., Gkatzima, O., Lupton, M., Koutroumani, M., Avramidou, D., Germanou, A., Jessen, F., Riedel-Heller, S., Sims, R., Letenneur, L., Dichgans, M., Heun, R., Kölsch, H., Schürmann, B., Herold, C., Lacour, A., Drichel, D., Hoffman, P., Kornhuber, J., Morón, F. J., Feulner, T., van den Bussche, H., Lawlor, B., Lynch, A., Mann, D., Smith, A. D., Warden, D., Wilcock, G., Heuser, I., Wiltgang, J., Rubinsztein, D. C., Frölich, L., Hüll, M., Mayo, K., Livingston, G., Bass, N. J., Gurling, H., McQuillen, A., Gwilliam, R., Deloukas, P., Al-Chalabi, A., Eiriksdottir, G., Shaw, C. E., Singleton, A. B., Guerreiro, R., Jöckel, K. H., Klopp, N., Wichmann, H. E., Graff-Radford, N. R., Ma, L., Bisceglio, G., Sleegers, K., Fisher, E., Warner, N., Pickering-Brown, S., Becker, Tim, Goate, A. M., Fiévet, N., Huentelman, M. W., Gill, M., Brown, K., Bellenguez, C., Kamboh, M. I., Keller, L., Barberger-Gateau, P., McGuiness, B., Larson, E. B., Green, R., Myers, A. J., Dufouil, C., Todd, S., Wallon, D., DeStafano, A. L., Love, S., Rogaeva, E., Gallacher, J., St George-Hyslop, P., Clarimon, J., Lleo, A., Bayer, A., Tsuang, D. W., Yu, L., Tsolaki, M., Bis, J. C., Bossù, P., Spalletta, G., Proitsi, P., Collinge, J., Sorbi, S., Sanchez-Garcia, F., Fox, N. C., Hardy, J., Deniz Naranjo, M. C., Bosco, P., Beecham, G. W., Clarke, R., Brayne, C., Galimberti, D., Mancuso, M., Matthews, F., Initiative, European Alzheimer's Disease, Disease, Genetic and Environmental Risk in Alzheimer's, Consortium, Alzheimer's Disease Genetic, Epidemiology, Cohorts for Heart and Aging Research in Genomic, Moebus, S., Grenier-Boley, B., Mecocci, P., Del Zompo, M., Maier, W., Hampel, H., Pilotto, A., Bullido, M., Panza, F., Caffarra, P., Nacmias, B., Gilbert, J. R., Neurology, Radiology & Nuclear Medicine, and Epidemiology
Subjects: Male, Apolipoprotein E, epidemiology [Alzheimer Disease], SORL1, Medizin, genetics [Alzheimer Disease], Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, PICALM, Cohort Studies, Alzheimer Disease, ddc:570, PSEN2, Genetics, medicine, Humans, Genetic Predisposition to Disease, Age of Onset, Aged, Genetic association, Aged, 80 and over, Middle Aged, medicine.disease, Genetic Loci, Case-Control Studies, Female, Human medicine, Alzheimer's disease, statistics & numerical data [Genome-Wide Association Study], Genome-Wide Association Study
Abstract: Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 x 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
Published: 2013

35. Partizipative Destinationsentwicklungsprojekte: Ein vorläufiges Resümee aus Südtirol

Author: Volgger, Michael, Pechlaner, Harald, Lun, L., Pichler, S., Herntrei, M., Kofink, L., Raich, F., Volgger, Michael, Pechlaner, Harald, Lun, L., Pichler, S., Herntrei, M., Kofink, L., and Raich, F.
Published: 2017

36. Sistemi di innovazione regionale I: prospettive di collaborazione delle istituzioni nel management territoriale dell’Alto Adige

Author: Scuttari, A., Volgger, Michael, Pechlaner, Harald, Pichler, S., Scuttari, A., Volgger, Michael, Pechlaner, Harald, and Pichler, S.
Published: 2017

37. The practice of destination governance: A comparative analysis of key dimensions and underlying concepts

Author: Volgger, Michael, Pechlaner, H., Pichler, S., Volgger, Michael, Pechlaner, H., and Pichler, S.
Abstract: Most of research on destination governance focuses on reporting the results of single case studies, whose findings are often related to the particularities of the specific destinations considered. As a result, there is little (empirical) consistency in underlying principles and dimensions of destination governance. To overcome this gap, this paper presents a combined (re-)analysis of multiple qualitative case studies and empirically develops destination governance dimensions from a practitioner point of view. Findings show that theoretical conceptualisation of destination governance and practical foci differ in some respects: In contrast to governance theory, practitioners refer more to context, process and change.
Published: 2017

38. The Eight Superconducting Quadrupoles for the ISR High-Luminosity Insertion

Author: Billan, J., Henrichsen, K. N., Laeger, H., Lebrun, Ph., Perin, R., Pichler, S., Pugin, P., Resegotti, L., Rohmig, P., Tortschanoff, T., Yerdier, A., Walckiers, L., Wolf, R., and Newman, W. S., editor
Published: 1980
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39. A novel Alzheimer disease locus located near the gene encoding tau protein

Author: Jun, G., Ibrahim-Verbaas, C.A., Vronskaya, M., Lambert, J.-., Chung, J., Naj, A.C., Kunkle, B.W., Wang, L.-., Bis, J.C., Bellenguez, C., Harold, D., Lunetta, K.L., Destefano, A.L., Grenier-Boley, B., Sims, R., Beecham, G.W., Smith, A.V., Chouraki, V., Hamilton-Nelson, K.L., Ikram, M.A., Fievet, N., Denning, N., Martin, E.R., Schmidt, H., Kamatani, Y., Dunstan, M.L., Valladares, O., Laza, A.R., Zelenika, D., Ramirez, A., Foroud, T.M., Choi, S.-., Boland, A., Becker, T., Kukull, W.A., Van Der Lee, S.J., Pasquier, F., Cruchaga, C., Beekly, D., Fitzpatrick, A.L., Hanon, O., Gill, M., Barber, R., Gudnason, V., Campion, D., Love, S., Bennett, D.A., Amin, N., Berr, C., Tsolaki, M., Buxbaum, J.D., Lopez, O.L., Deramecourt, V., Fox, N.C., Cantwell, L.B., Tárraga, L., Dufouil, C., Hardy, J., Crane, P.K., Eiriksdottir, G., Hannequin, D., Clarke, R., Evans, D., Mosley, T.H., Letenneur, L., Brayne, C., Maier, W., De Jager, P., Emilsson, V., Dartigues, J.-., Hampel, H., Kamboh, M.I., De Bruijn, R.F.A.G., Tzourio, C., Pastor, P., Larson, E.B., Rotter, J.I., O'Donovan, M.C., Montine, T.J., Nalls, M.A., Mead, S., Reiman, E.M., Jonsson, P.V., Holmes, C., St George-Hyslop, P.H., Boada, M., Passmore, P., Wendland, J.R., Schmidt, R., Morgan, K., Winslow, A.R., Powell, J.F., Carasquillo, M., Younkin, S.G., Jakobsdóttir, J., Kauwe, J.S.K., Wilhelmsen, K.C., Rujescu, D., Nöthen, M.M., Hofman, A., Jones, L., Haines, J.L., Psaty, B.M., Van Broeckhoven, C., Holmans, P., Launer, L.J., Mayeux, R., Lathrop, M., Goate, A.M., Escott-Price, V., Seshadri, S., Pericak-Vance, M.A., Amouyel, P., Williams, J., Van Duijn, C.M., Schellenberg, G.D., Farrer, L.A., Adams, P.M., Albert, M.S., Albin, R.L., Apostolova, L.G., Arnold, S.E., Asthana, S., Atwood, C.S., Baldwin, C.T., Barmada, M.M., Barnes, L.L., Beach, T.G., Becker, J.T., Bigio, E.H., Bird, T.D., Blacker, D., Boeve, B.F., Bowen, J.D., Boxer, A., Burke, J.R., Cairns, N.J., Cao, C., Carlson, C.S., Carlsson, C.M., Carney, R.M., Carrasquillo, M.M., Carroll, S.L., Chui, H.C., Clark, D.G., Corneveaux, J., Cribbs, D.H., Crocco, E.A., De Jager, P.L., Decarli, C., Dekosky, S.T., Yesim Demirci, F., Dick, M., Dickson, D.W., Doody, R.S., Duara, R., Ertekin-Taner, N., Faber, K.M., Fairchild, T.J., Fallon, K.B., Farlow, M.R., Ferris, S., Frosch, M.P., Galasko, D.R., Gearing, M., Geschwind, D.H., Ghetti, B., Gilbert, J.R., Glass, J.D., Graff-Radford, N.R., Green, R.C., Growdon, J.H., Hakonarson, H., Hamilton, R.L., Harrell, L.E., Head, E., Honig, L.S., Huebinger, R.M., Huentelman, M.J., Hulette, C.M., Hyman, B.T., Jarvik, G.P., Jicha, G.A., Jin, L., Karydas, A., Kaye, J.A., Kim, R., Koo, E.H., Kowall, N.W., Kramer, J.H., Laferla, F.M., Lah, J.J., Leverenz, J.B., Levey, A.I., Ge, L., Lieberman, A.P., Lin, C., Lyketsos, C.G., Mack, W.J., Marson, D.C., Martiniuk, F., Mash, D.C., Masliah, E., Mccormick, W.C., Mccurry, S.M., Mcdavid, A.N., Mckee, A.C., Mesulam, M., Miller, B.L., Miller, C.A., Miller, J.W., Morris, J.C., Mukherjee, S., Murrell, J.R., Myers, A.J., O'Bryant, S., Olichney, J.M., Pankratz, V.S., Parisi, J.E., Partch, A., Paulson, H.L., Perry, W., Peskind, E., Petersen, R.C., Pierce, A., Poon, W.W., Potter, H., Quinn, J.F., Raj, A., Raskind, M., Reisberg, B., Reisch, J.S., Reitz, C., Ringman, J.M., Roberson, E.D., Rogaeva, E., Rosen, H.J., Rosenberg, R.N., Royall, D.R., Sager, M.A., Sano, M., Saykin, A.J., Schneider, J.A., Schneider, L.S., Seeley, W.W., Smith, A.G., Sonnen, J.A., Spina, S., Stern, R.A., Tanzi, R.E., Thornton-Wells, T.A., Trojanowski, J.Q., Troncoso, J.C., Tsuang, D.W., Van Deerlin, V.M., Van Eldik, L.J., Vardarajan, B.N., Vinters, H.V., Vonsattel, J.P., Weintraub, S., Welsh-Bohmer, K.A., Williamson, J., Wishnek, S., Woltjer, R.L., Wright, C.B., Chuang-Kuo, W., Chang-En, Y., Lei, Y., Thomas, C., Gerrish, A., Chapman, J., Stretton, A., Morgan, A., Oldham, H., Owen, M.J., Kehoe, P.G., Medway, C., Brown, K., Lord, J., Turton, J., Hooper, N.M., Vardy, E., Warren, J.D., Schott, J.M., Uphill, J., Hollingworth, P., Ryan, N., Rossor, M., Collinge, J., Ben-Shlomo, Y., Makrina, D., Gkatzima, O., Lupton, M., Koutroumani, M., Avramidou, D., Germanou, A., Jessen, F., Riedel-Heller, S., Dichgans, M., Heun, R., Kölsch, H., Schürmann, B., Herold, C., Lacour, A., Drichel, D., Hoffmann, P., Kornhuber, J., Wei, G., Feulner, T., Mayhaus, M., Pichler, S., Riemenschneider, M., van den Bussche, H., Lawlor, B., Lynch, A., Mann, D., Smith, A.D., Warden, D., Wilcock, G., Heuser, I., Wiltfang, J., Frölich, L., Hüll, M., Mayo, K., Livingston, G., Bass, N.J., Gurling, H., Mcquillin, A., Gwilliam, R., Deloukas, P., Al-Chalabi, A., Shaw, C.E., Singleton, A.B., Guerreiro, R., Russo, G., Jöckel, K., Moebus, S., Klopp, N., Wichmann, H.-., Li, M., Bisceglio, G., Fisher, E., Warner, N., Pickering-Brown, S., Craig, D., Johnston, J.A., Mcguinness, B., Todd, S., Rubinsztein, D.C., Lovestone, S., Bayer, A., Gallacher, J., Proitsi, P., Ortega-Cubero, Saraadams, P., Albert, M., Albin, R., Apostolova, L., Arnold, S., Atwood, C., Baldwin, C., Barmada, M., Barnes, L., Beach, T., Becker, J., Bigio, E., Bird, T., Boeve, B., Bowen, J., Burke, J., Cairns, N., Carlson, C., Carlsson, C., Carney, R., Carrasquillo, M., Carroll, S., Chui, H., Clark, D., Cribbs, D., Crocco, E., De Jager PL, Dekosky, S., Demirci, F., Dickson, D., Doody, R., Faber, K., Fairchild, T., Fallon, K., Farlow, M., Frosch, M., Galasko, D., Geschwind, D., Gilbert, J., Glass, J., Graff-Radford, N., Green, R., Growdon, J., Hamilton, R., Harrell, L., Honig, L., Huebinger, R., Huentelman, M., Hulette, C., Hyman, B., Jarvik, G., Jicha, G., Kauwe, J., Kaye, J., Koo, E., Kowall, N., Kramer, J., Laferla, F., Lah, J., Leverenz, J., Levey, A., Li, G., Lieberman, A., Lopez, O., Lyketsos, C., Mack, W., Marson, D., Mash, D., Mccormick, W., Mccurry, S., Mcdavid, A., Mckee, A., Miller, B., Miller, C., Miller, J., Morris, J., Murrell, J., Myers, A., Olichney, J., Pankratz, V., Parisi, J., Paulson, H., Petersen, R., Poon, W., Quinn, J., Reisch, J., Ringman, J., Roberson, E., Rosen, H., Rosenberg, R., Royall, D., Sager, M., Saykin, A., Schneider, J., Schneider, L., Seeley, W., Smith, A., Sonnen, J., Stern, R., Tanzi, R., Thornton-Wells, T., Trojanowski, J., Troncoso, J., Tsuang, D., Van Deerlin VM, Van Eldik LJ, Vardarajan, B., Vinters, H., Vonsattel, J., Welsh-Bohmer, K., Woltjer, R., Wright, C., Wu, C., Yu, C., Yu, L., Au, R., Wolf, P., Beiser, A., Satizabal, C., Uitterlinden, A., Rivadeneira, F., Koudstaal, P., Longstreth WT Jr, Kuller, L., Lumley, T., Rice, K., Harris, T., Nalls, M., Marksteiner, J., Dal-Bianco, P., Töglhofer, A., Freudenberger, P., Ransmayr, G., Benke, T., Toeglhofer, A., Boerwinkle, E., Bressler, J., Fornage, M., Morón, F., Hernández, I., Roca, M., Mauleón, A., Alegret, M., Ramírez-Lorca, R., González-Perez, A., Alpérovitch, A., Alvarez, V., Barberger-Gateau, P., Bettens, K., Bossù, P., Brice, A., Bullido, M., Caffara, P., Clarimon, J., Combarros, O., Coto, E., Del Zampo, M., Delepine, M., Deniz Naranjo MC, Epelbaum, J., Fratiglioni, L., Galimberti, D., Graff, C., Hiltunen, M., Ingelsson, M., Keller, L., Lannfelt, L., Llèo, A., Mancuso, M., Mateo, I., Mecocci, P., Nacmias, B., Panza, F., Pilotto, A., Garcia, F., Scarpini, E., Seripa, D., Sleegers, K., Soininen, H., Sorbi, S., Spalletta, G., Wallon, D., Owen, M., Kehoe, P., Hooper, N., Warren, J., Schott, J., Gu, W., Bass, N., Shaw, C., Singleton, A., Wichmann, H., Ma, L., Johnston, J., Rubinsztein, D., Ortega-Cubero, S., Epidemiology, Neurology, and Internal Medicine
Subjects: 0301 basic medicine, Apolipoprotein E, Apolipoprotein E4, Single-nucleotide polymorphism, Locus (genetics), Genome-wide association study, genetics [Alzheimer Disease], MAPT protein, human, tau Proteins, Polymorphism, Single Nucleotide, Article, Chromosomes, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Settore BIO/13 - Biologia Applicata, Humans, ddc:610, Polymorphism, Molecular Biology, Biology, genetics [Apolipoprotein E4], Genetic association, Temporal cortex, Genetics, Pair 17, Haplotype, Single Nucleotide, 3. Good health, Chromosome 17 (human), genetics [tau Proteins], Chemistry, 030104 developmental biology, Psychiatry and Mental Health, Chromosomes, Human, Pair 17, Genome-Wide Association Study, Settore MED/26 - Neurologia, Human medicine, Psychology, 030217 neurology & neurosurgery, Human
Abstract: APOE epsilon 4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE epsilon 4+ (10 352 cases and 9207 controls) and APOE epsilon 4 - (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE e4 status. Suggestive associations (P < 1x10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE epsilon 4+: 1250 cases and 536 controls; APOE epsilon 4 -: 718 cases and 1699 controls). Among APOE epsilon 4 - subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P = 5.8 x 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE epsilon 4+ subjects (CR1 and CLU) or APOE epsilon 4 - subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P = 1.6 x 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P
Published: 2016

40. The Pros and Cons of Sick Pay Schemes: A Method to Test for Contagious Presenteeism and Shirking Behavior

Author: Pichler, S and Ziebarth, N.R
Subjects: jel:I12, jel:J22, jel:I13, jel:I18, jel:J28, Sickness Insurance, Sick Pay, Presenteeism, Contagious Diseases, Infections, Negative Externalities, Shirking, jel:J32
Abstract: This paper proposes a test for the existence and the degree of contagious presenteeism and negative externalities in sickness insurance schemes. First, we theoretically decompose moral hazard into shirking and contagious presenteeism behavior. Then we derive testable conditions for reduced shirking, increased presenteeism, and the level of overall moral hazard when benefits are cut. We implement the test empirically exploiting German sick pay reforms and administrative industry-level data on certified sick leave by diagnoses. The labor supply adjustment for contagious diseases is significantly smaller than for non-contagious diseases, providing evidence for contagious presenteeism and negative externalities which arise in form of infections.
Published: 2015

41. The Information and Communication Technology User Role: Implications for the Work Role and Inter-Role Spillover

Author: Piszczek, MM, Pichler, S, Turel, O, Greenhaus, J, Piszczek, MM, Pichler, S, Turel, O, and Greenhaus, J
Abstract: Management and organization research has traditionally focused on employees' work role and the interface between their work and family roles. We suggest that persons assume a third role in modern society that is relevant to work and organizations, namely the Information and Communication Technology User (ICTU) role. Based on role theory and boundary theory, we develop propositions about the characteristics of this role, as well as how ICTU role characteristics are related to boundary spanning activity, inter-role spillover with the work role, and work role performance. To this end, we first conceptualize the ICTU role and its associations with work and family roles. We then apply identity theory and boundary management theory to advance our understanding of how the ICTU role is related to criteria that are important to individuals and to organizations, namely self-selection into certain types of work roles and positive and negative inter-role spillover. The implications of this role for theory, research, and practice in management and organizations are discussed.
Published: 2016

42. Part IV Italy: Case 12 Passeiertal/Val Passiria

Author: Volgger, Michael, Pichler, S., Herntrei, M., Volgger, Michael, Pichler, S., and Herntrei, M.
Abstract: The case of Passeiertal/Val Passiria illustrates how typologies of governance forms help to differentiate cases with concentrated authority from cases with an even distribution of power. In particular, it exemplifies how the interplay between DMOs and powerful private businesses can improve the competitive position of a destination. First, Passeiertal/Val Passiria has managed to develop a common strategy in collaboration with the biggest private player. Second, the whole destination is positioned with the themes driven by the player. The case also shows that property rights theory and principal agent theory may provide useful explanations as to how sustainable destination governance can be improved in situations of significant power asymmetries.
Published: 2015

43. Part IV Italy: Case 10 Tisens/Tesimo

Author: Volgger, Michael, Pichler, S., Herntrei, M., Volgger, Michael, Pichler, S., and Herntrei, M.
Abstract: The case of Tisens/Tesimo illustrates the critical role of governance in the course of a destination life cycle. In particular, it exemplifies how improving the effectiveness and efficiency of destination governance has the potential to relaunch stagnating or declining destinations. First, Tisens/Tesimo has managed to improve its effectiveness by developing a common strategy in a participatory manner. Second, improving efficiency in networking through an increase in trust also seems to have supported the process of recovery. However, the challenge is to establish cost-efficient collaboration while maintaining the dynamic and adaptive capacity associated with low levels of centralization. In achieving this balance, the destination raises issues about collaborative efficiency.
Published: 2015

44. Part IV Italy: Case 11 Naturns/Naturno

Author: Volgger, Michael, Pichler, S., Herntrei, M., Volgger, Michael, Pichler, S., and Herntrei, M.
Abstract: The extant literature distinguishes sharply between corporate and community models of destination governance. In contrast, the case of Naturns/Naturno illustrates how a specific mixture of corporate and community approaches in governance can yield positive results. In particular, it shows how the existence of a network core characterized by integrative entrepreneurial leadership, an element that would in the first instance be associated with a corporate-driven destination, turns out to be a potential driver of a successful community-oriented destination development. In Naturns/Naturno, through its integrative entrepreneurial behavior, a hotel consortium has been influential in leading the transformation of the whole destination toward increased quality, strategic coherence, and innovativeness, while maintaining its community orientation.
Published: 2015

45. Frontotemporal dementia and its subtypes: A genome-wide association study

Author: Ferrari, R, Hernandez, DG, Nalls, MA, Rohrer, JD, Ramasamy, A, Kwok, JBJ, Dobson-Stone, C, Brooks William S., BS, Schofield, PR, Halliday, GM, Hodges, JR, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, NJ, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, ML, Nilsson, K, Nilsson, C, Mackenzie, IRA, Hsiung, GYR, Mann, DMA, Grafman, J, Morris, CM, Attems, J, Griffiths, TD, McKeith, IG, Thomas, AJ, Pietrini, P, Huey, ED, Wassermann, EM, Baborie, A, Jaros, E, Tierney, MC, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, JB, Schlachetzki, JCM, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, VM, Grossman, M, Trojanowski, JQ, Van der Zee, J, Deschamps, W, Van Langenhove, T, Cruts, M, Van Broeckhoven, C, Cappa, SF, Le Ber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, JE, Hjermind, LE, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, MN, Ferrari, R, Hernandez, DG, Nalls, MA, Rohrer, JD, Ramasamy, A, Kwok, JBJ, Dobson-Stone, C, Brooks William S., BS, Schofield, PR, Halliday, GM, Hodges, JR, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, NJ, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, ML, Nilsson, K, Nilsson, C, Mackenzie, IRA, Hsiung, GYR, Mann, DMA, Grafman, J, Morris, CM, Attems, J, Griffiths, TD, McKeith, IG, Thomas, AJ, Pietrini, P, Huey, ED, Wassermann, EM, Baborie, A, Jaros, E, Tierney, MC, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, JB, Schlachetzki, JCM, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, VM, Grossman, M, Trojanowski, JQ, Van der Zee, J, Deschamps, W, Van Langenhove, T, Cruts, M, Van Broeckhoven, C, Cappa, SF, Le Ber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, JE, Hjermind, LE, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, and Rossor, MN
Abstract: Background: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods: We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10-8) single-nucleotide polymorphisms. Findings: We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10-8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10-8; odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10-9; 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10-8, 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10-7; 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci migh
Published: 2014

46. Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease

Author: Escott-Price, V, Bellenguez, C, Wang, LS (Li-San), Choi, SH, Harold, D, Jones, L, Holmans, P, Gerrish, A, Vedernikov, A, Richards, A, DeStefano, AL, Lambert, JC, Verbaas, Carla, Naj, AC, Sims, R, Jun, G, Bis, JC, Beecham, GW, Grenier-Boley, B, Russo, G, Thornton-Wells, TA, Denning, N, Smith, AV, Chouraki, V, Thomas, C, Ikram, Arfan, Zelenika, D, Vardarajan, BN, Kamatani, Y, Lin, CF, Schmidt, Heléna, Kunkle, B, Dunstan, ML, Vronskaya, M, Johnson, AD, Ruiz, A, Bihoreau, MT, Reitz, C, Pasquier, F, Hollingworth, P, Hanon, O, Fitzpatrick, AL, Buxbaum, JD, Campion, D, Crane, PK, Baldwin, C, Becker, T, Gudnason, V, Cruchaga, C, Craig, D, Amin, Najaf, Berr, C, Lopez, OL, De Jager, PL, Deramecourt, V, Johnston, JA, Evans, D, Lovestone, S, Letenneur, L, Hernandez, I, Rubinsztein, DC, Eiriksdottir, G, Sleegers, K (Kristel), Goate, AM, Fievet, N, Huentelman, MJ, Gill, M, Brown, K, Kamboh, MI, Keller, L, Barberger-Gateau, P, McGuinness, B, Larson, EB, Myers, AJ, Dufouil, C, Todd, S, Wallon, D, Love, S, Rogaeva, E, Gallacher, J, St George-Hyslop, P, Clarimon, J, Lleo, A, Bayer, A, Tsuang, DW, Yu, L, Tsolaki, M, Bossu, P, Spalletta, G, Proitsi, P, Collinge, J, Sorbi, S, Garcia, FS, Fox, NC, Hardy, J, Naranjo, MCD, Bosco, P, Clarke, R, Brayne, C, Galimberti, D, Scarpini, E, Bonuccelli, U, Mancuso, M, Siciliano, G, Moebus, S, Mecocci, P, Del Zompo, M, Maier, W, Hampel, H, Pilotto, A, Frank-Garcia, A, Panza, F, Solfrizzi, V, Caffarra, P, Nacmias, B, Perry, W, Mayhaus, M, Lannfelt, L, Hakonarson, H, Pichler, S, Carrasquillo, MM, Ingelsson, M, Beekly, D, Alvarez, V, Zou, FG, Valladares, O, Younkin, SG, Coto, E, Hamilton-Nelson, KL, Gu, W, Razquin, C, Pastor, P, Mateo, I, Owen, MJ, Faber, KM, Jonsson, PV, Combarros, O, O'Donovan, MC, Cantwell, LB, Soininen, H, Blacker, D, Mead, S, Mosley, TH, Bennett, DA, Harris, TB, Fratiglioni, L, Holmes, C, Bruijn, Renee, Passmore, P, Montine, TJ, Bettens, K, Rotter, JI, Brice, A, Morgan, K, Foroud, TM, Kukull, WA, Hannequin, D, Powell, JF, Nalls, MA, Ritchie, K, Lunetta, KL, Kauwe, JSK, Boerwinkle, E, Riemenschneider, M, Boada, M, Hiltunen, M, Martin, ER, Schmidt, R, Rujescu, D, Dartigues, JF, Mayeux, R, Tzourio, C, Hofman, Bert, Nothen, MM, Graff, C, Psaty, BM, Haines, JL, Lathrop, M, Pericak-Vance, MA, Launer, LJ (Lenore), van Broeckhoven, C, Farrer, LA, Duijn, Cornelia, Ramirez, A, Seshadri, S, Schellenberg, GD, Amouyel, P, Williams, J, Escott-Price, V, Bellenguez, C, Wang, LS (Li-San), Choi, SH, Harold, D, Jones, L, Holmans, P, Gerrish, A, Vedernikov, A, Richards, A, DeStefano, AL, Lambert, JC, Verbaas, Carla, Naj, AC, Sims, R, Jun, G, Bis, JC, Beecham, GW, Grenier-Boley, B, Russo, G, Thornton-Wells, TA, Denning, N, Smith, AV, Chouraki, V, Thomas, C, Ikram, Arfan, Zelenika, D, Vardarajan, BN, Kamatani, Y, Lin, CF, Schmidt, Heléna, Kunkle, B, Dunstan, ML, Vronskaya, M, Johnson, AD, Ruiz, A, Bihoreau, MT, Reitz, C, Pasquier, F, Hollingworth, P, Hanon, O, Fitzpatrick, AL, Buxbaum, JD, Campion, D, Crane, PK, Baldwin, C, Becker, T, Gudnason, V, Cruchaga, C, Craig, D, Amin, Najaf, Berr, C, Lopez, OL, De Jager, PL, Deramecourt, V, Johnston, JA, Evans, D, Lovestone, S, Letenneur, L, Hernandez, I, Rubinsztein, DC, Eiriksdottir, G, Sleegers, K (Kristel), Goate, AM, Fievet, N, Huentelman, MJ, Gill, M, Brown, K, Kamboh, MI, Keller, L, Barberger-Gateau, P, McGuinness, B, Larson, EB, Myers, AJ, Dufouil, C, Todd, S, Wallon, D, Love, S, Rogaeva, E, Gallacher, J, St George-Hyslop, P, Clarimon, J, Lleo, A, Bayer, A, Tsuang, DW, Yu, L, Tsolaki, M, Bossu, P, Spalletta, G, Proitsi, P, Collinge, J, Sorbi, S, Garcia, FS, Fox, NC, Hardy, J, Naranjo, MCD, Bosco, P, Clarke, R, Brayne, C, Galimberti, D, Scarpini, E, Bonuccelli, U, Mancuso, M, Siciliano, G, Moebus, S, Mecocci, P, Del Zompo, M, Maier, W, Hampel, H, Pilotto, A, Frank-Garcia, A, Panza, F, Solfrizzi, V, Caffarra, P, Nacmias, B, Perry, W, Mayhaus, M, Lannfelt, L, Hakonarson, H, Pichler, S, Carrasquillo, MM, Ingelsson, M, Beekly, D, Alvarez, V, Zou, FG, Valladares, O, Younkin, SG, Coto, E, Hamilton-Nelson, KL, Gu, W, Razquin, C, Pastor, P, Mateo, I, Owen, MJ, Faber, KM, Jonsson, PV, Combarros, O, O'Donovan, MC, Cantwell, LB, Soininen, H, Blacker, D, Mead, S, Mosley, TH, Bennett, DA, Harris, TB, Fratiglioni, L, Holmes, C, Bruijn, Renee, Passmore, P, Montine, TJ, Bettens, K, Rotter, JI, Brice, A, Morgan, K, Foroud, TM, Kukull, WA, Hannequin, D, Powell, JF, Nalls, MA, Ritchie, K, Lunetta, KL, Kauwe, JSK, Boerwinkle, E, Riemenschneider, M, Boada, M, Hiltunen, M, Martin, ER, Schmidt, R, Rujescu, D, Dartigues, JF, Mayeux, R, Tzourio, C, Hofman, Bert, Nothen, MM, Graff, C, Psaty, BM, Haines, JL, Lathrop, M, Pericak-Vance, MA, Launer, LJ (Lenore), van Broeckhoven, C, Farrer, LA, Duijn, Cornelia, Ramirez, A, Seshadri, S, Schellenberg, GD, Amouyel, P, and Williams, J
Abstract: Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Published: 2014

47. Enhancing Tourism Destinations Through Promoting the Variety and Uniqueness of Attractions Offered by Minority Populations: An Exploratory Study Towards a New Research Field

Author: Pechlaner, Harald, Beritelli, P., Pichler, S., Pechlaner, Harald, Beritelli, P., and Pichler, S.
Abstract: Purpose: Minority areas, with their cultural distinctiveness and a strong tendency to cultivate and preserve cultural identities, can offer guests special added value as tourist destinations. This study seeks to address whether and to what extent locals and guests of tourist areas populated by minority populations perceive and are aware of the uniqueness, variety and potential of the minority in a region. Design/methodology/approach: Research has already been developed that analyses the inter‐relations between the local population and tourism, but is scarce regarding national minorities and tourism. This paper pursues a new research field focusing on the potential of tourist destinations that offer specialised characteristics due to their cultural, ethnic or minority populations. The authors carried out an empirical study using quantitative, standardised questionnaires in 2008 in two minority areas: South Tyrol, Italy (which has a Ladin minority population) as well as Transylvania, Romania (which has a German and Hungarian minority population). The South Tyrol situation is doubly unusual, because the Ladin minority population is a minority within the German minority region in Italy.Findings: The study shows that ethnic minority populations can definitely offer added value for holidaymakers in tourist destinations. The special interest and attraction of these types of holiday stay for guests is explained, above all, by the varied cuisine and the locals' proficiency in languages (South Tyrol) as well as the specific architecture and the more extensive cultural offerings (Transylvania). In Transylvania no significant differences and in South Tyrol significant differences in the perception of the special cultural situation by locals and guests have been observed. Research limitations/implications: This study was confined to 250 interviewees per group and study region, due to budget restrictions. Compared to the volume of research on native population and tourism, resear
Published: 2014

48. Uzgoj, košnja i uskladištenje silažnog kukuruza u AG-BAG fleksibilno crijevo

Author: R.Zimmer, S. Pichler, S. Košutić, D. Jelošek and Silvio Košutić
Subjects: silažni kukuruz, silažna preša, crijeva od folije
Abstract: Uzgoj, košnja i uskladištenje hibrida kukuruza PR34N43 obavljeno je na OPG „ Simental Commercxe“ Osijek, lokacija Tenja. Nakon žetve pšenice obavljena je plitka obrada strništa tanjuračom, a zatim podrivanje u dubinu 60 do 70 cm i tanjuranje tla. U jesen 2007. u osnovnoj gnojidbi na tlo je raspodijeljeno mineralno gnojivo NPK formulacije 7:20:30 u količini 430 kg ha-1, a zatim je s okretnim plugom obavljeno oranje u dubinu 30 cm. U proljeće je sjetvospremačem zatvorena zimska brazda i zatim raspodjeljena UREA u dozi 350 kg ha -1, nakon čega slijedi fina priprema tla sa sjetvospremačem s kratkim klinovima i 25. travnja sjetva sijačicom Maxem-6. Prije nicanja usjeva obavljena je zaštita s Lumax-om u količini od 2 l ha-1, a poslije nicanja korišten je Motivel u dozi 1 l ha-1 + Cambio u dozi od 2 l ha-1. Kultivacija nije obavljena. Košnja je obavljena silažnim kombajnom Claas Jaguar 900 s Corn crekerom i adapterom RU 600 Extra, koji ima 4 bubnja i zahvaća 8 redi kukuruza. Dodatak (inokulant, aditiv) za stočnu hranu u količini od 500 g na 100 l vode dodavan je Spotlyt uređajem na silažnoj preši AG-BAG G 6000 Europe. Prosječni urod silažnog kukuruza PR34N43 bio je 52030 kg ha-1, a spremanje je obavljeno od 3 do 15. rujna. Silažni kukuruz uskladišten je u polietilensko crijevo promjera 244 cm i duljine 60 m. Analizirani uzorak silaže uzet 4. rujna imao je 74 boda (dobra silaža), a uzet 12. rujna imao je 50 bodova (osrednja silaža). Na istraživanom OPG u 2008. god. krma je uskladištena u ukupno 19 crijeva od folije dimenzije 60 m duljine i 2, 44 m širine, odnosno temeljem ispunjenosti crijeva 90-92% spremljeno je 266 do 285 vagona silažnog kukuruza.
Published: 2009

49. Checkliste Gender & Medizin

Author: Steinböck, S, Pichler, S, and Hammer, H
Subjects: ddc: 610, 610 Medical sciences, Medicine
Abstract: [for full text, please go to the a.m. URL], 12. Grazer Konferenz - Qualität der Lehre: Skills and Attitudes
Published: 2009
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50. DESIGN, TEST AND PERFORMANCE OF THE LIQUID HELIUM CRYOSTATS FOR THE LEP SUPERCONDUCTING QUADRUPOLE MAGNETS

Author: Blessing, H., primary, Lebrun, Ph., additional, Pichler, S., additional, Taylor, T.M., additional, and Trinquart, G., additional
Published: 1988
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