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Language
- English (5)
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Keywords
- Data sharing (1)
- Eye tracking (1)
- biomarker (1)
- brainstem (1)
- cerebellum (1)
- global change (1)
- habitat destruction (1)
- land use (1)
- locus coeruleus (1)
- pupillometry (1)
Hudson, Lawrence N. ; Newbold, Tim ; Contu, Sara ; Hill, Samantha L. L. ; Lysenko, Igor ; Palma, Adriana de ; Phillips, Helen R. P. ; Senior, Rebecca A. ; Bennett, Dominic J. ; Booth, Hollie ; Choimes, Argyrios ; Correia, David L. P. ; Day, Julie ; Echeverria-Londono, Susy ; Garon, Morgan ; Harrison, Michelle L. K. ; Ingram, Daniel J. ; Jung, Martin ; Kemp, Victoria ; Kirkpatrick, Lucinda ; Martin, Callum D. ; Pan, Yuan ; White, Hannah J. ; Aben, Job ; Abrahamczyk, Stefan ; Adum, Gilbert B. ; Aguilar-Barquero, Virginia ; Aizen, Marcelo ; Ancrenaz, Marc ; Arbelaez-Cortes, Enrique ; Armbrecht, Inge ; Azhar, Badrul ; Azpiroz, Adrián B. ; Baeten, Lander ; Báldi, András ; Banks, John E. ; Barlow, Jos ; Batáry, Péter ; Bates, Adam J. ; Bayne, Erin M. ; Beja, Pedro ; Berg, Åke ; Berry, Nicholas J. ; Bicknell, Jake E. ; Bihn, Jochen H. ; Böhning-Gaese, Katrin ; Boekhout, Teun ; Boutin, Celine ; Bouyer, Jeremy ; Brearley, Francis Q. ; Brito, Isabel ; Brunet, Jörg ; Buczkowski, Grzegorz ; Buscardo, Erika ; Cabra-Garcia, Jimmy ; Calvino-Cancela, Maria ; Cameron, Sydney A. ; Cancello, Eliana M. ; Carrijo, Tiago F. ; Carvalho, Anelena L. ; Castro, Helena ; Castro-Luna, Alejandro Antonio ; Cerda, Rolando ; Cerezo, Alexis ; Chauvat, Matthieu ; Clarke, Frank M. ; Cleary, Daniel F. R. ; Connop, Stuart P. ; D'Aniello, Biagio ; Silva, Pedro Giovani da ; Darvill, Ben ; Dauber, Jens ; Dejean, Alain ; Diekötter, Tim ; Dominguez-Haydar, Yamileth ; Dormann, Carsten F. ; Dumont, Bertrand ; Dures, Simon G. ; Dynesius, Mats ; Edenius, Lars ; Elek, Zoltan ; Entling, Martin H. ; Farwig, Nina ; Fayle, Tom M. ; Felicioli, Antonio ; Felton, Annika M. ; Ficetola, Gentile Francesco ; Filgueiras, Bruno K. C. ; Fonte, Steve J. ; Fraser, Lauchlan H. ; Fukuda, Daisuke ; Furlani, Dario ; Ganzhorn, Jörg U. ; Garden, Jenni G. ; Gheler-Costa, Carla ; Giordani, Paolo ; Giordano, Simonetta ; Gottschalk, Marco S. ; Goulson, Dave ; Gove, Aaron D. ; Grogan, James ; Hanley, Mick E. ; Hanson, Thor ; Hashim, Nor R. ; Hawes, Joseph E. ; Hébert, Christian ; Helden, Alvin J. ; Henden, John-André ; Hernández, Lionel ; Herzog, Felix ; Higuera-Diaz, Diego ; Hilje, Branko ; Horgan, Finbarr G. ; Horvath, Roland ; Hylander, Kristoffer ; Horvath, Roland ; Isaacs-Cubides, Paola ; Ishitani, Mashiro ; Jacobs, Carmen T. ; Jaramillo, Victor J. ; Jauker, Birgit ; Jonsell, Matts ; Jung, Thomas S. ; Kapoor, Vena ; Kati, Vassiliki ; Katovai, Eric ; Kessler, Michael ; Knop, Eva ; Kolb, Annette ; Körösi, Àdám ; Lachat, Thibault ; Lantschner, Victoria ; Le Féon, Violette ; LeBuhn, Gretchen ; Légaré, Jean-Philippe ; Letcher, Susan G. ; Littlewood, Nick A. ; López-Quintero, Carlos A. ; Louhaichi, Mounir ; Lövei, Gabor L. ; Lucas-Borja, Manuel Esteban ; Luja, Victor H. ; Maeto, Kaoru ; Magura, Tibor ; Mallari, Neil Aldrin D. ; Marin-Spiotta, Erika ; Marshall, Edward Jon P. ; Martínez, Eliana ; Mayfield, Margaret M. ; Mikusinski, Gregorz ; Milder, Jeffery C. ; Miller, James R. ; Morales, Carolina L. ; Muriithi-Muchane, Mary Nyawira ; Muchane, Muchai ; Naidoo, Robin ; Nakamura, Akihiro ; Naoe, Shoji ; Nates-Parra, Guiomar ; Navarerete Gutierrez, Dario A. ; Neuschulz, Eike Lena ; Noreika, Norbertas ; Norfolk, Olivia ; Noriega, Jorge Ari ; Nöske, Nicole M. ; O'Dea, Niall ; Oduro, William ; Ofori-Boateng, Caleb ; Oke, Chris O. ; Osgathorpe, Lynne M. ; Paritsis, Juan ; Parrah, Alejandro ; Pelegrin, Nicolás ; Peres, Carlos A. ; Persson, Anna S. ; Petanidou, Theodora ; Phalan, Ben ; Philips, T. Keith ; Poveda, Katja ; Power, Eileen F. ; Presley, Steven J. ; Proença, Vânia ; Quaranta, Marino ; Quintero, Carolina ; Redpath-Downing, Nicola A. ; Reid, J. Leighton ; Reis, Yana T. ; Ribeiro, Danilo B. ; Richardson, Barbara A. ; Richardson, Michael J. ; Robles, Carolina A. ; Römbke, Jörg ; Romero-Duque, Luz Piedad ; Rosselli, Loreta ; Rossiter, Stephen J. ; Roulston, T'ai H. ; Rousseau, Laurent ; Sadler, Jonathan P. ; Sáfián, Szbolcs ; Saldaña-Vásquez, Romeo A. ; Samnegård, Ulrika ; Schüepp, Christof ; Schweiger, Oliver ; Sedlock, Jodi L. ; Shahabuddin, Ghazala ; Sheil, Douglas ; Silva, Fernando A. B. ; Slade, Eleanor ; Smith-Pardo, Allan H. ; Sodhi, Navjot S. ; Somarriba, Eduardo J. ; Sosa, Ramón A. ; Stout, Jane C. ; Struebig, Matthew J. ; Sung, Yik-Hei ; Threlfall, Caragh G. ; Tonietto, Rebecca ; Tóthmérész, Béla ; Tscharntke, Teja ; Turner, Edgar C. ; Tylianakis, Jason M. ; Vanbergen, Adam J. ; Vassilev, Kiril ; Verboven, Hans A. F. ; Vergara, Carlos H. ; Vergara, Pablo M. ; Verhulst, Jort ; Walker, Tony R. ; Wang, Yanping ; Watling, James I. ; Wells, Konstans ; Williams, Christopher D. ; Willig, Michael R. ; Woinarski, John Casimir Zichy ; Wolf, Jan H. D. ; Woodcock, Ben A. ; Yu, Douglas W. ; Zailsev, Andreys ; Collen, Ben ; Ewers, Rob M. ; Mace, Georgina M. ; Purves, Drew W. ; Scharlemann, Jörn P. W. ; Pervis, Andy
Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
Koromina, Maria ; Ravi, Ashvin ; Panagiotaropoulou, Georgia ; Schilder, Brian M. ; Humphrey, Jack ; Braun, Alice ; Bidgeli, Tim ; Chatzinakos, Chris ; Coombes, Brandon ; Kim, Jaeyoung ; Liu, Xiaoxi ; Terao, Chikashi ; O'Connell, Kevin S. ; Adams, Mark ; Adolfsson, Rolf ; Alda, Martin ; Alfredsson, Lars ; Andlauer, Till ; Andreassen, Ole A. ; Antoniou, Anastasia ; Baune, Bernhard T. ; Bengesser, Susanne ; Biernacka, Joanna ; Boehnke, Michael ; Bosch, Rosa ; Cairns, Murray ; Carr, Vaughan J. ; Casas Brugué, Miquel ; Catts, Stanley ; Cichon, Sven ; Corvin, Aiden ; Craddock, Nicholas ; Dafnas, Konstantinos ; Dalkner, Nina ; Dannlowski, Udo ; Degenhardt, Franziska ; Di Florio, Arianna ; Dikeos, Dimitris ; Fellendorf, Frederike Tabea ; Ferentinos, Panagiotis ; Forstner, Andreas Josef ; Forty, Liz ; Frye, Mark ; Fullerton, Janice M. ; Gawlik, Micha ; Gizer, Ian R. ; Gordon-Smith, Katherine ; Green, Melissa J. ; Grigoroiu-Serbanescu, Maria ; Guzman-Parra, José ; Hahn, Tim ; Henskens, Frans ; Hillert, Jan ; Jablensky, Assen V. ; Jones, Lisa ; Jones, Ian ; Jonsson, Lina ; Kelsoe, John R. ; Kircher, Tilo ; Kirov, George ; Kittel-Schneider, Sarah ; Kogevinas, Manolis ; Landén, Mikael ; Leboyer, Marion ; Lenger, Melanie ; Lissowska, Jolanta ; Lochner, Christine ; Loughland, Carmel ; MacIntyre, Donald ; Martin, Nicholas G. ; Maratou, Eirini ; Mathews, Carol A. ; Mayoral, Fermı́n ; McElroy, Susan L. ; McGregor, Nathaniel W. ; McIntosh, Andrew M. ; McQuillin, Andrew ; Michie, Patricia ; Milanova, Vihra ; Mitchell, Philip B. ; Moutsatsou, Paraskevi ; Mowry, Bryan ; Müller-Myhsok, Bertram ; Myers, Richard M. ; Nenadić, Igor ; Nöthen, Markus Maria ; O'Donovan, Claire ; O'Donovan, Michael ; Ophoff, Roel André ; Owen, Michael J. ; Pantelis, Christos ; Pato, Carlos ; Pato, Michele T. ; Patrinos, George P. ; Pawlak, Joanna M. ; Perlis, Roy H. ; Porichi, Evgenia ; Posthuma, Danielle ; Ramos-Quiroga, Josep Antoni ; Reif, Andreas ; Reininghaus, Eva Z. ; Ribasés, Marta ; Rietschel, Marcella ; Schall, Ulrich ; Schulze, Thomas Gerd ; Scott, Laura J. ; Scott, Rodney J. ; Serretti, Alessandro ; Shannon Weickert, Cynthia ; Smoller, Jordan W. ; Soler Artigas, Marı́a ; Stein, Dan J. ; Streit, Fabian ; Toma, Claudio ; Tooney, Paul ; Vieta, Eduard ; Vincent, John B. ; Waldman, Irwin D. ; Weickert, Thomas ; Witt, Stephanie H. ; Hong, Kyung Sue ; Ikeda, Masashi ; Iwata, Nakao ; Świątkowska, Beata ; Won, Hong-Hee ; Edenberg, Howard J. ; Ripke, Stephan ; Raj, Towfique ; Coleman, Jonathan R. I. ; Mullins, Niamh
Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
Bast, Nico ; Mason, Luke ; Freitag, Christine M. ; Smith, Tim ; Portugal, Ana Maria ; Poustka, Luise ; Banaschewski, Tobias ; Johnson, Mark
Background: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Methods: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil-dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. Results: We observed decreased saccade duration (∆M = −0.50, CI [−0.21, −0.78]) and amplitude (∆M = −0.42, CI [−0.12, −0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil-dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. Conclusions: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo-)motor coordination and attention function in ASD.
Escott-Price, Valentina ; Bellenguez, Céline ; Wang, Li-San ; Choi, Seung-Hoan ; Harold, Denise ; Jones, Lesley ; Holmans, Peter ; Gerrish, Amy ; Vedernikov, Alexey ; Richards, Alexander ; DeStefano, Anita L. ; Lambert, Jean-Charles ; Ibrahim-Verbaas, Carla A. ; Naj, Adam C. ; Sims, Rebecca ; Jun, Gyungah ; Bis, Joshua C. ; Beecham, Gary W. ; Grenier-Boley, Benjamin ; Russo, Giancarlo ; Thornton-Wells, Tricia A. ; Denning, Nicola ; Smith, Albert V. ; Chouraki, Vincent ; Thomas, Charlene ; Ikram, M. Arfan ; Zelenika, Diana ; Vardarajan, Badri N. ; Kamatani, Yoichiro ; Lin, Chiao-Feng ; Schmidt, Helena ; Kunkle, Brian ; Dunstan, Melanie L. ; Vronskaya, Maria ; Johnson, Andrew D. ; Ruiz, Agustin ; Bihoreau, Marie-Thérèse ; Reitz, Christiane ; Pasquier, Florence ; Hollingworth, Paul ; Hanon, Olivier ; Fitzpatrick, Annette L. ; Buxbaum, Joseph D. ; Campion, Dominique ; Crane, Paul K. ; Baldwin, Clinton ; Becker, Tim ; Gudnason, Vilmundur ; Cruchaga, Carlos ; Craig, David ; Amin, Najaf ; Berr, Claudine ; Lopez, Oscar L. ; Jager, Philip L. De ; Deramecourt, Vincent ; Johnston, Janet A. ; Evans, Denis ; Lovestone, Simon ; Letenneur, Luc ; Hernández, Isabel ; Rubinsztein, David C. ; Eiriksdottir, Gudny ; Sleegers, Kristel ; Goate, Alison M. ; Fiévet, Nathalie ; Huentelman, Matthew J. ; Gill, Michael ; Brown, Kristelle ; Kamboh, M. Ilyas ; Keller, Lina ; Barberger-Gateau, Pascale ; McGuinness, Bernadette ; Larson, Eric B. ; Myers, Amanda J. ; Dufouil, Carole ; Todd, Stephen ; Wallon, David ; Love, Seth ; Rogaeva, Ekaterina ; Gallacher, John ; St George-Hyslop, Peter ; Clarimon, Jordi ; Lleo, Alberto ; Bayer, Anthony ; Tsuang, Debby W. ; Yu, Lei ; Tsolaki, Magda ; Bossù, Paola ; Spalletta, Gianfranco ; Proitsi, Petra ; Collinge, John ; Sorbi, Sandro ; Sanchez Garcia, Florentino ; Fox, Nick C. ; Hardy, John ; Deniz Naranjo, Maria Candida ; Bosco, Paolo ; Clarke, Robert ; Brayne, Carol ; Galimberti, Daniela ; Scarpini, Elio ; Bonuccelli, Ubaldo ; Mancuso, Michelangelo ; Siciliano, Gabriele ; Moebus, Susanne ; Mecocci, Patrizia ; Del Zompo, Maria ; Maier, Wolfgang ; Hampel, Harald ; Pilotto, Alberto ; Frank-García, Ana ; Panza, Francesco ; Solfrizzi, Vincenzo ; Caffarra, Paolo ; Nacmias, Benedetta ; Perry, William ; Mayhaus, Manuel ; Lannfelt, Lars ; Hakonarson, Hakon ; Pichler, Sabrina ; Carrasquillo, Minerva M. ; Ingelsson, Martin ; Beekly, Duane ; Alvarez, Victoria ; Zou, Fanggeng ; Valladares, Otto ; Younkin, Steven G. ; Coto, Eliecer ; Hamilton-Nelson, Kara L. ; Gu, Wei ; Razquin, Cristina ; Pastor, Pau ; Mateo, Ignacio ; Owen, Michael J. ; Faber, Kelley M. ; Jonsson, Palmi V. ; Combarros, Onofre ; O'Donovan, Michael C. ; Cantwell, Laura B. ; Soininen, Hilkka ; Blacker, Deborah ; Mead, Simon ; Mosley, Thomas H. ; Bennett, David A. ; Harris, Tamara B. ; Fratiglioni, Laura ; Holmes, Clive ; Bruijn, Renee F. A. G. de ; Passmore, Peter ; Montine, Thomas J. ; Bettens, Karolien ; Rotter, Jerome I. ; Brice, Alexis ; Morgan, Kevin ; Foroud, Tatiana M. ; Kukull, Walter A. ; Hannequin, Didier ; Powell, John F. ; Nalls, Michael A. ; Ritchie, Karen ; Lunetta, Kathryn L. ; Kauwe, John S. K. ; Boerwinkle, Eric ; Riemenschneider, Matthias ; Boada, Mercè ; Hiltunen, Mikko ; Martin, Eden R. ; Schmidt, Reinhold ; Rujescu, Dan ; Dartigues, Jean-François ; Mayeux, Richard ; Tzourio, Christophe ; Hofman, Albert ; Nöthen, Markus Maria ; Graff, Caroline ; Psaty, Bruce M. ; Haines, Jonathan L. ; Lathrop, Mark ; Pericak-Vance, Margaret Ann ; Launer, Lenore J. ; Broeckhoven, Christine Van ; Farrer, Lindsay A. ; Duijn, Cornelia M. van ; Ramirez, Alfredo ; Seshadri, Sudha ; Schellenberg, Gerard D. ; Amouyel, Philippe ; Williams, Julie
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 = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) 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.
Randall, Joshua C. ; Winkler, Thomas W. ; Kutalik, Zoltán ; I. Berndt, Sonja ; Jackson, Anne U. ; Monda, Keri L. ; Kilpeläinen, Tuomas O. ; Esko, Tõnu ; Mägi, Reedik ; Li, Shengxu ; Workalemahu, Tsegaselassie ; Feitosa, Mary F. ; Croteau-Chonka, Damien C. ; Day, Felix R. ; Fall, Tove ; Ferreira, Teresa ; Gustafsson, Stefan ; Locke, Adam E. ; Mathieson, Iain ; Scherag, André ; Vedantam, Sailaja ; Wood, Andrew R. ; Liang, Liming ; Steinthorsdottir, Valgerdur ; Thorleifsson, Gudmar ; Dermitzakis, Emmanouil T. ; Dimas, Antigone S. ; Karpe, Fredrik ; Min, Josine L. ; Nicholson, George ; Clegg, Deborah J. ; Person, Thomas ; Krohn, Jon P. ; Bauer, Sabrina ; Buechler, Christa ; Eisinger, Kristina ; Bonnefond, Amélie ; Froguel, Philippe ; Hottenga, Jouke-Jan ; Prokopenko, Inga ; Waite, Lindsay L. ; Harris, Tamara B. ; Smith, Albert Vernon ; Shuldiner, Alan R. ; McArdle, Wendy L. ; Caulfield, Mark J. ; Munroe, Patricia B. ; Grönberg, Henrik ; Chen, Yii-Der Ida ; Li, Guo ; Beckmann, Jacques S. ; Johnson, Toby ; Thorsteinsdottir, Unnur ; Teder-Laving, Maris ; Khaw, Kay-Tee ; Wareham, Nicholas J. ; Zhao, Jing Hua ; Amin, Najaf ; Oostra, Ben A. ; Kraja, Aldi T. ; Province, Michael A. ; Cupples, L. Adrienne ; Heard-Costa, Nancy L. ; Kaprio, Jaakko ; Ripatti, Samuli ; Surakka, Ida ; Collins, Francis S. ; Saramies, Jouko ; Tuomilehto, Jaakko ; Jula, Antti ; Salomaa, Veikko ; Erdmann, Jeanette ; Hengstenberg, Christian ; Loley, Christina ; Schunkert, Heribert ; Lamina, Claudia ; Wichmann, Heinz Erich ; Albrecht, Eva ; Gieger, Christian ; Hicks, Andrew A. ; Johansson, Åsa ; Pramstaller, Peter P. ; Kathiresan, Sekar ; Speliotes, Elizabeth K. ; Penninx, Brenda W. J. H. ; Hartikainen, Anna-Liisa ; Jarvelin, Marjo-Riitta ; Gyllensten, Ulf ; Boomsma, Dorret I. ; Campbell, Harry ; Wilson, James F. ; Chanock, Stephen J. ; Farrall, Martin ; Goel, Anuj ; Medina-Gomez, Carolina ; Rivadeneira, Fernando ; Estrada, Karol ; Uitterlinden, André G. ; Hofman, Albert ; Zillikens, M. Carola ; Heijer, Martin den ; Kiemeney, Lambertus Adrianus ; Maschio, Andrea ; Hall, Per ; Tyrer, Jonathan ; Teumer, Alexander ; Völzke, Henry ; Kovacs, Peter ; Tönjes, Anke ; Mangino, Massimo ; Spector, Tim D. ; Hayward, Caroline ; Rudan, Igor ; Hall, Alistair S. ; Samani, Nilesh J. ; Attwood, Antony Paul ; Sambrook, Jennifer G. ; Hung, Joseph ; Palmer, Lyle J. ; Lokki, Marja-Liisa ; Sinisalo, Juha ; Boucher, Gabrielle ; Huikuri, Heikki ; Lorentzon, Mattias ; Ohlsson, Claes ; Eklund, Niina ; Eriksson, Johan G. ; Barlassina, Cristina ; Rivolta, Carlo ; Nolte, Ilja M. ; Snieder, Harold ; Klauw, Melanie M. van der ; Vliet-Ostaptchouk, Jana V. van ; Gejman, Pablo V. ; Shi, Jianxin ; Jacobs, Kevin B. ; Wang, Zhaoming ; Bakker, Stephan J. L. ; Mateo Leach, Irene ; Navis, Gerjan ; Harst, Pim van der ; Martin, Nicholas Gordon ; Medland, Sarah E. ; Montgomery, Grant W. ; Yang, Jian ; Chasman, Daniel I. ; Ridker, Paul M. ; Rose, Lynda M. ; Lehtimäki, Terho ; Raitakari, Olli ; Absher, Devin ; Iribarren, Carlos ; Basart, Hanneke ; Hovingh, Kees G. ; Hyppönen, Elina ; Power, Chris ; Power, Chris ; Anderson, Denise ; Beilby, John P. ; Hui, Jennie ; Jolley, Jennifer ; Sager, Hendrik ; Bornstein, Stefan R. ; Schwarz, Peter E. H. ; Kristiansson, Kati ; Perola, Markus ; Lindström, Jaana ; Swift, Amy J. ; Uusitupa, Matti ; Atalay, Mustafa ; Lakka, Timo A. ; Rauramaa, Rainer ; Bolton, Jennifer L. ; Fowkes, Gerry ; Fraser, Ross M. ; Price, Jackie F. ; Fischer, Krista ; KrjutÅ¡kov, Kaarel ; Metspalu, Andres ; Mihailov, Evelin ; Langenberg, Claudia ; Luan, Jian'an ; Ong, Ken K. ; Chines, Peter S. ; Keinanen-Kiukaanniemi, Sirkka M. ; Saaristo, Timo E. ; Edkins, Sarah ; Franks, Paul W. ; Hallmans, Göran ; Shungin, Dmitry ; Morris, Andrew David ; Palmer, Colin N. A. ; Erbel, Raimund ; Moebus, Susanne ; Nöthen, Markus Maria ; Pechlivanis, Sonali ; Hveem, Kristian ; Narisu, Narisu ; Hamsten, Anders ; Humphries, Steve E. ; Strawbridge, Rona J. ; Tremoli, Elena ; Grallert, Harald ; Thorand, Barbara ; Illig, Thomas ; Koenig, Wolfgang ; Müller-Nurasyid, Martina ; Peters, Annette ; Böhm, Bernhard O. ; Kleber, Marcus E. ; März, Winfried ; Winkelmann, Bernhard R. ; Kuusisto, Johanna ; Laakso, Markku ; Arveiler, Dominique ; Cesana, Giancarlo ; Kuulasmaa, Kari ; Virtamo, Jarmo ; Yarnell, John W. G. ; Kuh, Diana ; Wong, Andrew ; Lind, Lars ; Faire, Ulf de ; Gigante, Bruna ; Magnusson, Patrik K. E. ; Pedersen, Nancy L. ; Dedoussis, George ; Dimitriou, Maria ; Kolovou, Genovefa ; Kanoni, Stavroula ; Stirrups, Kathleen ; Bonnycastle, Lori L. ; Njølstad, Inger ; Wilsgaard, Tom ; Ganna, Andrea ; Rehnberg, Emil ; Hingorani, Aroon ; Kivimaki, Mika ; Kumari, Meena ; Assimes, Themistocles L. ; Barroso, Inês ; Boehnke, Michael ; Borecki, Ingrid B. ; Deloukas, Panos ; Fox, Caroline S. ; Frayling, Timothy ; Groop, Leif C. ; Haritunians, Talin ; Hunter, David ; Ingelsson, Erik ; Kaplan, Robert ; Mohlke, Karen L. ; North, Kari E. ; Lindgren, Cecilia M. ; Qi, Lu ; Loos, Ruth J. F. ; Heid, Iris M. ; Hirschhorn, Joel N. ; McCarthy, Mark I. ; Abecasis, Gonçalo R. ; Stefansson, Kari ; Strachan, David P. ; Schlessinger, David ; O'Connell, Jeffrey R. ; Duijn, Cornelia M. van
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
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