TY  - JOUR
A1  - Warrington, Nicole
A1  - Beaumont, Robin
A1  - Horikoshi, Momoko
A1  - Day, Felix R.
A1  - Helgeland, Øyvind
A1  - Laurin, Charles
A1  - Bacelis, Jonas
A1  - Peng, Shouneng
A1  - Hao, Ke
A1  - Feenstra, Bjarke
A1  - Wood, Andrew R.
A1  - Mahajan, Anubha
A1  - Tyrrell, Jessica
A1  - Robertson, Neil R.
A1  - Rayner, N. William
A1  - Qiao, Zhen
A1  - Moen, Gunn-Helen
A1  - Vaudel, Marc
A1  - Marsit, Carmen
A1  - Chen, Jia
A1  - Nodzenski, Michael
A1  - Schnurr, Theresia M.
A1  - Zafarmand, Mohammad Hadi
A1  - Bradfield, Jonathan P.
A1  - Grarup, Niels
A1  - Kooijman, Marjolein N.
A1  - Li-Gao, Ruifang
A1  - Geller, Frank
A1  - Ahluwalia, Tarunveer Singh
A1  - Paternoster, Lavinia
A1  - Rueedi, Rico
A1  - Huikari, Ville
A1  - Hottenga, Jouke-Jan
A1  - Lyytikäinen, Leo-Pekka
A1  - Cavadino, Alana
A1  - Metrustry, Sarah
A1  - Cousminer, Diana L.
A1  - Wu, Ying
A1  - Thiering, Elisabeth Paula
A1  - Wang, Carol A.
A1  - Have, Christian Theil
A1  - Vilor-Tejedor, Natalia
A1  - Joshi, Peter K.
A1  - Painter, Jodie N.
A1  - Ntalla, Ioanna
A1  - Myhre, Ronny
A1  - Pitkänen, Niina
A1  - van Leeuwen, Elisabeth M.
A1  - Joro, Raimo
A1  - Lagou, Vasiliki
A1  - Richmond, Rebecca C.
A1  - Espinosa, Ana
A1  - Barton, Sheila J.
A1  - Inskip, Hazel M.
A1  - Holloway, John W.
A1  - Santa-Marina, Loreto
A1  - Estivill, Xavier
A1  - Ang, Wei
A1  - Marsh, Julie A.
A1  - Reichetzeder, Christoph
A1  - Marullo, Letizia
A1  - Hocher, Berthold
A1  - Lunetta, Kathryn L.
A1  - Murabito, Joanne M.
A1  - Relton, Caroline L.
A1  - Kogevinas, Manolis
A1  - Chatzi, Leda
A1  - Allard, Catherine
A1  - Bouchard, Luigi
A1  - Hivert, Marie-France
A1  - Zhang, Ge
A1  - Muglia, Louis J.
A1  - Heikkinen, Jani
A1  - Morgen, Camilla S.
A1  - van Kampen, Antoine H. C.
A1  - van Schaik, Barbera D. C.
A1  - Mentch, Frank D.
A1  - Langenberg, Claudia
A1  - Scott, Robert A.
A1  - Zhao, Jing Hua
A1  - Hemani, Gibran
A1  - Ring, Susan M.
A1  - Bennett, Amanda J.
A1  - Gaulton, Kyle J.
A1  - Fernandez-Tajes, Juan
A1  - van Zuydam, Natalie R.
A1  - Medina-Gomez, Carolina
A1  - de Haan, Hugoline G.
A1  - Rosendaal, Frits R.
A1  - Kutalik, Zoltán
A1  - Marques-Vidal, Pedro
A1  - Das, Shikta
A1  - Willemsen, Gonneke
A1  - Mbarek, Hamdi
A1  - Müller-Nurasyid, Martina
A1  - Standl, Marie
A1  - Appel, Emil V. R.
A1  - Fonvig, Cilius Esmann
A1  - Trier, Caecilie
A1  - van Beijsterveldt, Catharina E. M.
A1  - Murcia, Mario
A1  - Bustamante, Mariona
A1  - Bonàs-Guarch, Sílvia
A1  - Hougaard, David M.
A1  - Mercader, Josep M.
A1  - Linneberg, Allan
A1  - Schraut, Katharina E.
A1  - Lind, Penelope A.
A1  - Medland, Sarah Elizabeth
A1  - Shields, Beverley M.
A1  - Knight, Bridget A.
A1  - Chai, Jin-Fang
A1  - Panoutsopoulou, Kalliope
A1  - Bartels, Meike
A1  - Sánchez, Friman
A1  - Stokholm, Jakob
A1  - Torrents, David
A1  - Vinding, Rebecca K.
A1  - Willems, Sara M.
A1  - Atalay, Mustafa
A1  - Chawes, Bo L.
A1  - Kovacs, Peter
A1  - Prokopenko, Inga
A1  - Tuke, Marcus A.
A1  - Yaghootkar, Hanieh
A1  - Ruth, Katherine S.
A1  - Jones, Samuel E.
A1  - Loh, Po-Ru
A1  - Murray, Anna
A1  - Weedon, Michael N.
A1  - Tönjes, Anke
A1  - Stumvoll, Michael
A1  - Michaelsen, Kim Fleischer
A1  - Eloranta, Aino-Maija
A1  - Lakka, Timo A.
A1  - van Duijn, Cornelia M.
A1  - Kiess, Wieland
A1  - Koerner, Antje
A1  - Niinikoski, Harri
A1  - Pahkala, Katja
A1  - Raitakari, Olli T.
A1  - Jacobsson, Bo
A1  - Zeggini, Eleftheria
A1  - Dedoussis, George V.
A1  - Teo, Yik-Ying
A1  - Saw, Seang-Mei
A1  - Montgomery, Grant W.
A1  - Campbell, Harry
A1  - Wilson, James F.
A1  - Vrijkotte, Tanja G. M.
A1  - Vrijheid, Martine
A1  - de Geus, Eco J. C. N.
A1  - Hayes, M. Geoffrey
A1  - Kadarmideen, Haja N.
A1  - Holm, Jens-Christian
A1  - Beilin, Lawrence J.
A1  - Pennell, Craig E.
A1  - Heinrich, Joachim
A1  - Adair, Linda S.
A1  - Borja, Judith B.
A1  - Mohlke, Karen L.
A1  - Eriksson, Johan G.
A1  - Widen, Elisabeth E.
A1  - Hattersley, Andrew T.
A1  - Spector, Tim D.
A1  - Kaehoenen, Mika
A1  - Viikari, Jorma S.
A1  - Lehtimaeki, Terho
A1  - Boomsma, Dorret I.
A1  - Sebert, Sylvain
A1  - Vollenweider, Peter
A1  - Sorensen, Thorkild I. A.
A1  - Bisgaard, Hans
A1  - Bonnelykke, Klaus
A1  - Murray, Jeffrey C.
A1  - Melbye, Mads
A1  - Nohr, Ellen A.
A1  - Mook-Kanamori, Dennis O.
A1  - Rivadeneira, Fernando
A1  - Hofman, Albert
A1  - Felix, Janine F.
A1  - Jaddoe, Vincent W. V.
A1  - Hansen, Torben
A1  - Pisinger, Charlotta
A1  - Vaag, Allan A.
A1  - Pedersen, Oluf
A1  - Uitterlinden, Andre G.
A1  - Jarvelin, Marjo-Riitta
A1  - Power, Christine
A1  - Hypponen, Elina
A1  - Scholtens, Denise M.
A1  - Lowe, William L.
A1  - Smith, George Davey
A1  - Timpson, Nicholas J.
A1  - Morris, Andrew P.
A1  - Wareham, Nicholas J.
A1  - Hakonarson, Hakon
A1  - Grant, Struan F. A.
A1  - Frayling, Timothy M.
A1  - Lawlor, Debbie A.
A1  - Njolstad, Pal R.
A1  - Johansson, Stefan
A1  - Ong, Ken K.
A1  - McCarthy, Mark I.
A1  - Perry, John R. B.
A1  - Evans, David M.
A1  - Freathy, Rachel M.
T1  - Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
JF  - Nature genetics
N2  - Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Y1  - 2019
SN  - 1061-4036
SN  - 1546-1718
VL  - 51
IS  - 5
SP  - 804
EP  - +
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Middeldorp, Christel M.
A1  - Mahajan, Anubha
A1  - Horikoshi, Momoko
A1  - Robertson, Neil R.
A1  - Beaumont, Robin N.
A1  - Bradfield, Jonathan P.
A1  - Bustamante, Mariona
A1  - Cousminer, Diana L.
A1  - Day, Felix R.
A1  - De Silva, N. Maneka
A1  - Guxens, Monica
A1  - Mook-Kanamori, Dennis O.
A1  - St Pourcain, Beate
A1  - Warrington, Nicole M.
A1  - Adair, Linda S.
A1  - Ahlqvist, Emma
A1  - Ahluwalia, Tarunveer Singh
A1  - Almgren, Peter
A1  - Ang, Wei
A1  - Atalay, Mustafa
A1  - Auvinen, Juha
A1  - Bartels, Meike
A1  - Beckmann, Jacques S.
A1  - Bilbao, Jose Ramon
A1  - Bond, Tom
A1  - Borja, Judith B.
A1  - Cavadino, Alana
A1  - Charoen, Pimphen
A1  - Chen, Zhanghua
A1  - Coin, Lachlan
A1  - Cooper, Cyrus
A1  - Curtin, John A.
A1  - Custovic, Adnan
A1  - Das, Shikta
A1  - Davies, Gareth E.
A1  - Dedoussis, George V.
A1  - Duijts, Liesbeth
A1  - Eastwood, Peter R.
A1  - Eliasen, Anders U.
A1  - Elliott, Paul
A1  - Eriksson, Johan G.
A1  - Estivill, Xavier
A1  - Fadista, Joao
A1  - Fedko, Iryna O.
A1  - Frayling, Timothy M.
A1  - Gaillard, Romy
A1  - Gauderman, W. James
A1  - Geller, Frank
A1  - Gilliland, Frank
A1  - Gilsanz, Vincente
A1  - Granell, Raquel
A1  - Grarup, Niels
A1  - Groop, Leif
A1  - Hadley, Dexter
A1  - Hakonarson, Hakon
A1  - Hansen, Torben
A1  - Hartman, Catharina A.
A1  - Hattersley, Andrew T.
A1  - Hayes, M. Geoffrey
A1  - Hebebrand, Johannes
A1  - Heinrich, Joachim
A1  - Helgeland, Oyvind
A1  - Henders, Anjali K.
A1  - Henderson, John
A1  - Henriksen, Tine B.
A1  - Hirschhorn, Joel N.
A1  - Hivert, Marie-France
A1  - Hocher, Berthold
A1  - Holloway, John W.
A1  - Holt, Patrick
A1  - Hottenga, Jouke-Jan
A1  - Hypponen, Elina
A1  - Iniguez, Carmen
A1  - Johansson, Stefan
A1  - Jugessur, Astanand
A1  - Kahonen, Mika
A1  - Kalkwarf, Heidi J.
A1  - Kaprio, Jaakko
A1  - Karhunen, Ville
A1  - Kemp, John P.
A1  - Kerkhof, Marjan
A1  - Koppelman, Gerard H.
A1  - Korner, Antje
A1  - Kotecha, Sailesh
A1  - Kreiner-Moller, Eskil
A1  - Kulohoma, Benard
A1  - Kumar, Ashish
A1  - Kutalik, Zoltan
A1  - Lahti, Jari
A1  - Lappe, Joan M.
A1  - Larsson, Henrik
A1  - Lehtimaki, Terho
A1  - Lewin, Alexandra M.
A1  - Li, Jin
A1  - Lichtenstein, Paul
A1  - Lindgren, Cecilia M.
A1  - Lindi, Virpi
A1  - Linneberg, Allan
A1  - Liu, Xueping
A1  - Liu, Jun
A1  - Lowe, William L.
A1  - Lundstrom, Sebastian
A1  - Lyytikainen, Leo-Pekka
A1  - Ma, Ronald C. W.
A1  - Mace, Aurelien
A1  - Magi, Reedik
A1  - Magnus, Per
A1  - Mamun, Abdullah A.
A1  - Mannikko, Minna
A1  - Martin, Nicholas G.
A1  - Mbarek, Hamdi
A1  - McCarthy, Nina S.
A1  - Medland, Sarah E.
A1  - Melbye, Mads
A1  - Melen, Erik
A1  - Mohlke, Karen L.
A1  - Monnereau, Claire
A1  - Morgen, Camilla S.
A1  - Morris, Andrew P.
A1  - Murray, Jeffrey C.
A1  - Myhre, Ronny
A1  - Najman, Jackob M.
A1  - Nivard, Michel G.
A1  - Nohr, Ellen A.
A1  - Nolte, Ilja M.
A1  - Ntalla, Ioanna
A1  - Oberfield, Sharon E.
A1  - Oken, Emily
A1  - Oldehinkel, Albertine J.
A1  - Pahkala, Katja
A1  - Palviainen, Teemu
A1  - Panoutsopoulou, Kalliope
A1  - Pedersen, Oluf
A1  - Pennell, Craig E.
A1  - Pershagen, Goran
A1  - Pitkanen, Niina
A1  - Plomin, Robert
A1  - Power, Christine
A1  - Prasad, Rashmi B.
A1  - Prokopenko, Inga
A1  - Pulkkinen, Lea
A1  - Raikkonen, Katri
A1  - Raitakari, Olli T.
A1  - Reynolds, Rebecca M.
A1  - Richmond, Rebecca C.
A1  - Rivadeneira, Fernando
A1  - Rodriguez, Alina
A1  - Rose, Richard J.
A1  - Salem, Rany
A1  - Santa-Marina, Loreto
A1  - Saw, Seang-Mei
A1  - Schnurr, Theresia M.
A1  - Scott, James G.
A1  - Selzam, Saskia
A1  - Shepherd, John A.
A1  - Simpson, Angela
A1  - Skotte, Line
A1  - Sleiman, Patrick M. A.
A1  - Snieder, Harold
A1  - Sorensen, Thorkild I. A.
A1  - Standl, Marie
A1  - Steegers, Eric A. P.
A1  - Strachan, David P.
A1  - Straker, Leon
A1  - Strandberg, Timo
A1  - Taylor, Michelle
A1  - Teo, Yik-Ying
A1  - Thiering, Elisabeth
A1  - Torrent, Maties
A1  - Tyrrell, Jessica
A1  - Uitterlinden, Andre G.
A1  - van Beijsterveldt, Toos
A1  - van der Most, Peter J.
A1  - van Duijn, Cornelia M.
A1  - Viikari, Jorma
A1  - Vilor-Tejedor, Natalia
A1  - Vogelezang, Suzanne
A1  - Vonk, Judith M.
A1  - Vrijkotte, Tanja G. M.
A1  - Vuoksimaa, Eero
A1  - Wang, Carol A.
A1  - Watkins, William J.
A1  - Wichmann, H-Erich
A1  - Willemsen, Gonneke
A1  - Williams, Gail M.
A1  - Wilson, James F.
A1  - Wray, Naomi R.
A1  - Xu, Shujing
A1  - Xu, Cheng-Jian
A1  - Yaghootkar, Hanieh
A1  - Yi, Lu
A1  - Zafarmand, Mohammad Hadi
A1  - Zeggini, Eleftheria
A1  - Zemel, Babette S.
A1  - Hinney, Anke
A1  - Lakka, Timo A.
A1  - Whitehouse, Andrew J. O.
A1  - Sunyer, Jordi
A1  - Widen, Elisabeth E.
A1  - Feenstra, Bjarke
A1  - Sebert, Sylvain
A1  - Jacobsson, Bo
A1  - Njolstad, Pal R.
A1  - Stoltenberg, Camilla
A1  - Smith, George Davey
A1  - Lawlor, Debbie A.
A1  - Paternoster, Lavinia
A1  - Timpson, Nicholas J.
A1  - Ong, Ken K.
A1  - Bisgaard, Hans
A1  - Bonnelykke, Klaus
A1  - Jaddoe, Vincent W. V.
A1  - Tiemeier, Henning
A1  - Jarvelin, Marjo-Riitta
A1  - Evans, David M.
A1  - Perry, John R. B.
A1  - Grant, Struan F. A.
A1  - Boomsma, Dorret I.
A1  - Freathy, Rachel M.
A1  - McCarthy, Mark I.
A1  - Felix, Janine F.
T1  - The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
BT  - design, results and future prospects
JF  - European journal of epidemiology
N2  - The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
KW  - Genetics
KW  - Consortium
KW  - Childhood traits and disorders
KW  - Longitudinal
Y1  - 2019
U6  - https://doi.org/10.1007/s10654-019-00502-9
SN  - 0393-2990
SN  - 1573-7284
VL  - 34
IS  - 3
SP  - 279
EP  - 300
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Mieth, Bettina
A1  - Kloft, Marius
A1  - Rodriguez, Juan Antonio
A1  - Sonnenburg, Soren
A1  - Vobruba, Robin
A1  - Morcillo-Suarez, Carlos
A1  - Farre, Xavier
A1  - Marigorta, Urko M.
A1  - Fehr, Ernst
A1  - Dickhaus, Thorsten
A1  - Blanchard, Gilles
A1  - Schunk, Daniel
A1  - Navarro, Arcadi
A1  - Müller, Klaus-Robert
T1  - Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies
JF  - Scientific reports
N2  - The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008-2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0.
Y1  - 2016
U6  - https://doi.org/10.1038/srep36671
SN  - 2045-2322
VL  - 6
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Dejonghe, Wim
A1  - Kuenen, Sabine
A1  - Mylle, Evelien
A1  - Vasileva, Mina
A1  - Keech, Olivier
A1  - Viotti, Corrado
A1  - Swerts, Jef
A1  - Fendrych, Matyas
A1  - Ortiz-Morea, Fausto Andres
A1  - Mishev, Kiril
A1  - Delang, Simon
A1  - Scholl, Stefan
A1  - Zarza, Xavier
A1  - Heilmann, Mareike
A1  - Kourelis, Jiorgos
A1  - Kasprowicz, Jaroslaw
A1  - Nguyen, Le Son Long
A1  - Drozdzecki, Andrzej
A1  - Van Houtte, Isabelle
A1  - Szatmari, Anna-Maria
A1  - Majda, Mateusz
A1  - Baisa, Gary
A1  - Bednarek, Sebastian York
A1  - Robert, Stephanie
A1  - Audenaert, Dominique
A1  - Testerink, Christa
A1  - Munnik, Teun
A1  - Van Damme, Daniel
A1  - Heilmann, Ingo
A1  - Schumacher, Karin
A1  - Winne, Johan
A1  - Friml, Jiri
A1  - Verstreken, Patrik
A1  - Russinova, Eugenia
T1  - Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification
JF  - Nature Communications
N2  - ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane.
Y1  - 2016
U6  - https://doi.org/10.1038/ncomms11710
SN  - 2041-1723
VL  - 7
SP  - 1959
EP  - 1968
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Thiede, Rasmus Christoph
A1  - Robert, Xavier
A1  - Stuebner, Konstanze
A1  - Dey, Saptarshi
A1  - Faruhn, Johannes
T1  - Sustained out-of-sequence shortening along a tectonically active segment of the Main Boundary thrust: The Dhauladhar Range in the northwestern Himalaya
JF  - Lithosphere
N2  - Competing hypotheses suggest that Himalayan topography is sustained and the plate convergence is accommodated either solely along the basal decollement, the Main Himalayan thrust (MHT), or more broadly, across multiple thrust faults. In the past, structural, geomorphic, and geodetic data of the Nepalese Himalaya have been used to constrain the geometry of the MHT and its shallow frontal thrust fault, known as Main Frontal thrust (MFT). The MHT flattens at depth and connects to a hinterland mid-crustal, steeper thrust ramp, located similar to 100 km north of the deformation front. There, the present-day convergence across the Himalaya is mostly accommodated by slip along the MFT. Despite a general agreement that in Nepal most of the shortening is accommodated along the MHT, some researchers have suggested the occurrence of persistent out-of-sequence shortening on interior faults near the Main Central thrust (MCT). Along the northwest Himalaya, in contrast, some of these characteristics of central Nepal are missing, suggesting along-strike variation of wedge deformation and MHT fault geometry. Here we present new field observations and seven zircon (U-Th)/He (ZHe) cooling ages combined with existing low-temperature data sets. In agreement with our previous findings, we suggest that the transect of cooling age patterns across the frontal Dhauladhar Range reveals that the Main Boundary thrust (MBT) is a primary fault, which has uplifted and sustained this spectacular mountain front since at least the late Miocene. Our results suggest that the MBT forms an similar to 40-km-long fault ramp before it soles into the MHT, and motion along it has exhumed rocks from depth of similar to 8-10 km. New three-dimensional thermokinematic modeling (using Pecube finite-element code) reveals that the observed ZHe and apatite fission track cooling ages can only be explained by sustained mean MBT slip rates between similar to 2.6 and 3.5 mm a(-1) since at least 8 Ma, which corresponds to a horizontal shortening rate of similar to 1.7-2.4 mm a(-1). We propose that the MBT is active today, despite a lack of definitive field or seismogenic evidence, and continues to accommodate crustal shorting by out-of-sequence faulting. Assuming that present-day geodetic shorting rates (similar to 14 +/- 2 mm a(-1)) across the northwest Himalaya have been sustained over geologic time scales, this implies that the MBT accommodated similar to 15% of the total Himalayan convergence since its onset. Furthermore, our modeling results imply that the MHT is missing a hinterland mid-crustal ramp further north.
Y1  - 2017
U6  - https://doi.org/10.1130/L630.1
SN  - 1941-8264
SN  - 1947-4253
VL  - 9
SP  - 715
EP  - 725
PB  - American Institute of Physics
CY  - Boulder
ER  - 
TY  - JOUR
A1  - Hinkel, Jochen
A1  - Lincke, Daniel
A1  - Vafeidis, Athanasios T.
A1  - Perrette, Mahé
A1  - Nicholls, Robert James
A1  - Tol, Richard S. J.
A1  - Marzeion, Ben
A1  - Fettweis, Xavier
A1  - Ionescu, Cezar
A1  - Levermann, Anders
T1  - Coastal flood damage and adaptation costs under 21st century sea-level rise
JF  - Proceedings of the National Academy of Sciences of the United States of America
N2  - Coastal flood damage and adaptation costs under 21st century sea-level rise are assessed on a global scale taking into account a wide range of uncertainties in continental topography data, population data, protection strategies, socioeconomic development and sea-level rise. Uncertainty in global mean and regional sea level was derived from four different climate models from the Coupled Model Intercomparison Project Phase 5, each combined with three land-ice scenarios based on the published range of contributions from ice sheets and glaciers. Without adaptation, 0.2-4.6% of global population is expected to be flooded annually in 2100 under 25-123 cm of global mean sea-level rise, with expected annual losses of 0.3-9.3% of global gross domestic product. Damages of this magnitude are very unlikely to be tolerated by society and adaptation will be widespread. The global costs of protecting the coast with dikes are significant with annual investment and maintenance costs of US$ 12-71 billion in 2100, but much smaller than the global cost of avoided damages even without accounting for indirect costs of damage to regional production supply. Flood damages by the end of this century are much more sensitive to the applied protection strategy than to variations in climate and socioeconomic scenarios as well as in physical data sources (topography and climate model). Our results emphasize the central role of long-term coastal adaptation strategies. These should also take into account that protecting large parts of the developed coast increases the risk of catastrophic consequences in the case of defense failure.
KW  - coastal flooding
KW  - climate change impact
KW  - loss and damage
Y1  - 2014
U6  - https://doi.org/10.1073/pnas.1222469111
SN  - 0027-8424
VL  - 111
IS  - 9
SP  - 3292
EP  - 3297
PB  - National Acad. of Sciences
CY  - Washington
ER  -