Browsing by Subject "Genetic correlation"

Sort by: Order: Results:

Now showing items 1-7 of 7
  • Bogl, Leonie H.; Kaye, Sanna M.; Ramo, Joel T.; Kangas, Antti J.; Soininen, Pasi; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Ortega-Alonso, Alfredo; Rissanen, Aila; Ala-Korpela, Mika; Kaprio, Jaakko; Pietilainen, Kirsi H. (2016)
    Objective. To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. Subjects and methods. Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (r(g)) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference >= 3 kg/m(2)). Results. Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (r(g) = 0.40), glycoprotein (r(g) = 0.37), serum triglycerides (r(g) = 0.36), BCAAs (r(g) = 0.30-0.40), HDL particle diameter (r(g) = -0.33) and HDL cholesterol (r(g) = -0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. Conclusions. A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. (C) 2015 Elsevier Inc. All rights reserved.
  • Project MinE ALS GWAS Consortium I; Schijven, Dick; Stevelink, Remi; McCormack, Mark; van Rheenen, Wouter; Luykx, Jurjen J.; Koeleman, Bobby P. C.; Veldink, Jan H.; Eriksson, Johan G.; Kälviäinen, Reetta; Kantanen, Anne-Mari; Lehesjoki, Anna-Elina; Palotie, Aarno (2020)
  • Siewert, Katherine M.; Klarin, Derek; Damrauer, Scott M.; Chang, Kyong Mi; Tsao, Philip S.; Assimes, Themistocles L.; Smith, George Davey; Voight, Benjamin F.; Anttila, Verneri; Palta, Priit; Muona, Mikko; Kallela, Kaarlo Mikko; Koiranen, Markku; Lehtimäki, Terho; Sarin, Antti-Pekka; Wedenoja, Juho; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Kurki, Mitja Ilari; Hämäläinen, Eija Inkeri; Eriksson, Johan G.; Salomaa, Veikko; Heikkilä, Kauko; Männikkö, Minna; Hiekkala, Marjo; Kajanne, Risto; Kaprio, Jaakko; Aromaa, Arpo J.; Raitakari, Olli; Järvelin, Marjo-Riitta; Wessman, Maija; Palotie, Aarno (2021)
    Background: Nearly a fifth of the world's population suffer from migraine headache, yet risk factors for this disease are poorly characterized. Methods: To further elucidate these factors, we conducted a genetic correlation analysis using cross-trait linkage disequilibrium (LD) score regression between migraine headache and 47 traits from the UK Biobank. We then tested for possible causality between these phenotypes and migraine, using Mendelian randomization. In addition, we attempted replication of our findings in an independent genome-wide association study (GWAS) when available. Results: We report multiple phenotypes with genetic correlation (P < 1.06 × 10-3) with migraine, including heart disease, type 2 diabetes, lipid levels, blood pressure, autoimmune and psychiatric phenotypes. In particular, we find evidence that blood pressure directly contributes to migraine and explains a previously suggested causal relationship between calcium and migraine. Conclusions: This is the largest genetic correlation analysis of migraine headache to date, both in terms of migraine GWAS sample size and the number of phenotypes tested. We find that migraine has a shared genetic basis with a large number of traits, indicating pervasive pleiotropy at migraine-associated loci.
  • Mullins, Niamh; Kang, JooEun; Campos, Adrian I.; Coleman, Jonathan R.I.; Edwards, Alexis C.; Galfalvy, Hanga; Levey, Daniel F.; Lori, Adriana; Shabalin, Andrey; Starnawska, Anna; Su, Mei-Hsin; Watson, Hunna J.; Adams, Mark; Awasthi, Swapnil; Gandal, Michael; Hafferty, Jonathan D.; Hishimoto, Akitoyo; Kim, Minsoo; Okazaki, Satoshi; Otsuka, Ikuo; Ripke, Stephan; Ware, Erin B.; Bergen, Andrew W.; Berrettini, Wade H.; Bohus, Martin; Brandt, Harry; Chang, Xiao; Chen, Wei J.; Chen, Hsi-Chung; Crawford, Steven; Crow, Scott; DiBlasi, Emily; Duriez, Philibert; Fernández-Aranda, Fernando; Fichter, Manfred M.; Gallinger, Steven; Glatt, Stephen J.; Gorwood, Philip; Guo, Yiran; Hakonarson, Hakon; Halmi, Katherine A.; Hwu, Hai-Gwo; Jain, Sonia; Jamain, Stéphane; Jiménez-Murcia, Susana; Johnson, Craig; Kaplan, Allan S.; Kaye, Walter H.; Keel, Pamela K.; Kennedy, James L.; Klump, Kelly L.; Li, Dong; Liao, Shih-Cheng; Lieb, Klaus; Lilenfeld, Lisa; Liu, Chih-Min; Magistretti, Pierre J.; Marshall, Christian R.; Mitchell, James E.; Monson, Eric T.; Myers, Richard M.; Pinto, Dalila; Powers, Abigail; Ramoz, Nicolas; Roepke, Stefan; Rozanov, Vsevolod; Scherer, Stephen W.; Schmahl, Christian; Sokolowski, Marcus; Strober, Michael; Thornton, Laura M.; Treasure, Janet; Tsuang, Ming T.; Witt, Stephanie H.; Woodside, D. Blake; Yilmaz, Zeynep; Zillich, Lea; Adolfsson, Rolf; Agartz, Ingrid; Air, Tracy M.; Alda, Martin; Alfredsson, Lars; Andreassen, Ole A.; Anjorin, Adebayo; Appadurai, Vivek; Soler Artigas, María; der Auwera, Sandra Van; Azevedo, M. Helena; Bass, Nicholas; Bau, Claiton H.D.; Baune, Bernhard T.; Bellivier, Frank; Berger, Klaus; Biernacka, Joanna M.; Bigdeli, Tim B.; Binder, Elisabeth B.; Boehnke, Michael; Boks, Marco P.; Bosch, Rosa; Braff, David L.; Bryant, Richard; Budde, Monika; Byrne, Enda M.; Cahn, Wiepke; Casas, Miguel; Castelao, Enrique; Cervilla, Jorge A.; Chaumette, Boris; Cichon, Sven; Corvin, Aiden; Craddock, Nicholas; Craig, David; Degenhardt, Franziska; Djurovic, Srdjan; Edenberg, Howard J.; Fanous, Ayman H.; Foo, Jerome C.; Forstner, Andreas J.; Frye, Mark; Fullerton, Janice M.; Gatt, Justine M.; Gejman, Pablo V.; Giegling, Ina; Grabe, Hans J.; Green, Melissa J.; Grevet, Eugenio H.; Grigoroiu-Serbanescu, Maria; Gutierrez, Blanca; Guzman-Parra, Jose; Hamilton, Steven P.; Hamshere, Marian L.; Hartmann, Annette; Hauser, Joanna; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Ising, Marcus; Jones, Ian; Jones, Lisa A.; Jonsson, Lina; Kahn, René S.; Kelsoe, John R.; Kendler, Kenneth S.; Kloiber, Stefan; Koenen, Karestan C.; Kogevinas, Manolis; Konte, Bettina; Krebs, Marie-Odile; Landén, Mikael; Lawrence, Jacob; Leboyer, Marion; Lee, Phil H.; Levinson, Douglas F.; Liao, Calwing; Lissowska, Jolanta; Lucae, Susanne; Mayoral, Fermin; McElroy, Susan L.; McGrath, Patrick; McGuffin, Peter; McQuillin, Andrew; Medland, Sarah E.; Mehta, Divya; Melle, Ingrid; Milaneschi, Yuri; Mitchell, Philip B.; Molina, Esther; Morken, Gunnar; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Nievergelt, Caroline M.; Nimgaonkar, Vishwajit; Nöthen, Markus M.; O’Donovan, Michael C.; Ophoff, Roel A.; Owen, Michael J.; Pato, Carlos; Pato, Michele T.; Penninx, Brenda W.J.H.; Pimm, Jonathan; Pistis, Giorgio; Potash, James B.; Power, Robert A.; Preisig, Martin; Quested, Digby; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Ribasés, Marta; Richarte, Vanesa; Rietschel, Marcella; Rivera, Margarita; Roberts, Andrea; Roberts, Gloria; Rouleau, Guy A.; Rovaris, Diego L.; Rujescu, Dan; Sánchez-Mora, Cristina; Sanders, Alan R.; Schofield, Peter R.; Schulze, Thomas G.; Scott, Laura J.; Serretti, Alessandro; Shi, Jianxin; Shyn, Stanley I.; Sirignano, Lea; Sklar, Pamela; Smeland, Olav B.; Smoller, Jordan W.; Sonuga-Barke, Edmund J.S.; Spalletta, Gianfranco; Strauss, John S.; Świątkowska, Beata; Trzaskowski, Maciej; Turecki, Gustavo; Vilar-Ribó, Laura; Vincent, John B.; Völzke, Henry; Walters, James T.R.; Shannon Weickert, Cynthia; Weickert, Thomas W.; Weissman, Myrna M.; Williams, Leanne M.; Wray, Naomi R.; Zai, Clement C.; Ashley-Koch, Allison E.; Beckham, Jean C.; Hauser, Elizabeth R.; Hauser, Michael A.; Kimbrel, Nathan A.; Lindquist, Jennifer H.; McMahon, Benjamin; Oslin, David W.; Qin, Xuejun; Mattheisen, Manuel; Abdellaoui, Abdel; Adams, Mark J.; Agerbo, Esben; Andlauer, Till F.M.; Bacanu, Silviu-Alin; Bækvad-Hansen, Marie; Beekman, Aartjan T.F.; Bryois, Julien; Buttenschøn, Henriette N.; Bybjerg-Grauholm, Jonas; Cai, Na; Christensen, Jane Hvarregaard; Clarke, Toni-Kim; Colodro-Conde, Lucía; Couvy-Duchesne, Baptiste; Craddock, Nick; Crawford, Gregory E.; Davies, Gail; Derks, Eske M.; Direk, Nese; Dolan, Conor V.; Dunn, Erin C.; Eley, Thalia C.; Escott-Price, Valentina; Hassan Kiadeh, Farnush Farhadi; Finucane, Hilary K.; Frank, Josef; Gaspar, Héléna A.; Gill, Michael; Goes, Fernando S.; Gordon, Scott D.; Weinsheimer, Shantel Marie; Wellmann, Jürgen; Willemsen, Gonneke; Wu, Yang; Xi, Simon; Yang, Jian; Zhang, Futao; Arolt, Volker; Boomsma, Dorret I.; Dannlowski, Udo; de Geus, E.J.C.; Depaulo, J. Raymond; Domenici, Enrico; Domschke, Katharina; Esko, Tõnu; Grove, Jakob; Hall, Lynsey S.; Hansen, Christine Søholm; Hansen, Thomas F.; Herms, Stefan; Hickie, Ian B.; Homuth, Georg; Horn, Carsten; Hottenga, Jouke-Jan; Hougaard, David M.; Howard, David M.; Jansen, Rick; Jorgenson, Eric; Knowles, James A.; Kohane, Isaac S.; Kraft, Julia; Kretzschmar, Warren W.; Kutalik, Zoltán; Li, Yihan; Lind, Penelope A.; MacIntyre, Donald J.; MacKinnon, Dean F.; Maier, Robert M.; Maier, Wolfgang; Marchini, Jonathan; Mbarek, Hamdi; Middeldorp, Christel M.; Mihailov, Evelin; Milani, Lili; Mondimore, Francis M.; Montgomery, Grant W.; Mostafavi, Sara; Nauck, Matthias; Ng, Bernard; Nivard, Michel G.; Nyholt, Dale R.; O’Reilly, Paul F.; Oskarsson, Hogni; Hayward, Caroline; Heath, Andrew C.; Lewis, Glyn; Li, Qingqin S.; Madden, Pamela A.F.; Magnusson, Patrik K.; Martin, Nicholas G.; McIntosh, Andrew M.; Metspalu, Andres; Mors, Ole; Nordentoft, Merete; Paciga, Sara A.; Pedersen, Nancy L.; Painter, Jodie N.; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Peterson, Roseann E.; Peyrot, Wouter J.; Posthuma, Danielle; Quiroz, Jorge A.; Qvist, Per; Rice, John P.; Riley, Brien P.; Mirza, Saira Saeed; Schoevers, Robert; Schulte, Eva C.; Shen, Ling; Sigurdsson, Engilbert; Sinnamon, Grant C.B.; Smit, Johannes H.; Smith, Daniel J.; Stefansson, Hreinn; Steinberg, Stacy; Streit, Fabian; Strohmaier, Jana; Tansey, Katherine E.; Teismann, Henning; Teumer, Alexander; Thompson, Wesley; Thomson, Pippa A.; Thorgeirsson, Thorgeir E.; Traylor, Matthew; Treutlein, Jens; Trubetskoy, Vassily; Uitterlinden, André G.; Umbricht, Daniel; der Auwera, Sandra Van; van Hemert, Albert M.; Viktorin, Alexander; Visscher, Peter M.; Wang, Yunpeng; Webb, Bradley T.; Perlis, Roy H.; Porteous, David J.; Schaefer, Catherine; Stefansson, Kari; Tiemeier, Henning; Uher, Rudolf; Werge, Thomas; Lewis, Cathryn M.; Breen, Gerome; Børglum, Anders D.; Sullivan, Patrick F.; O’Connell, Kevin S.; Coombes, Brandon; Qiao, Zhen; Als, Thomas D.; Børte, Sigrid; Charney, Alexander W.; Drange, Ole Kristian; Gandal, Michael J.; Hagenaars, Saskia P.; Ikeda, Masashi; Kamitaki, Nolan; Krebs, Kristi; Panagiotaropoulou, Georgia; Schilder, Brian M.; Sloofman, Laura G.; Winsvold, Bendik S.; Won, Hong-Hee; Abramova, Liliya; Adorjan, Kristina; Al Eissa, Mariam; Albani, Diego; Alliey-Rodriguez, Ney; Antilla, Verneri; Antoniou, Anastasia; Baek, Ji Hyun; Bauer, Michael; Beins, Eva C.; Bergen, Sarah E.; Birner, Armin; Bøen, Erlend; Brum, Murielle; Brumpton, Ben M.; Brunkhorst-Kanaan, Nathalie; Byerley, William; Cairns, Murray; Casas, Miquel; Cervantes, Pablo; Cruceanu, Cristiana; Cuellar-Barboza, Alfredo; Cunningham, Julie; Curtis, David; Czerski, Piotr M.; Dale, Anders M.; Dalkner, Nina; David, Friederike S.; Dobbyn, Amanda L.; Douzenis, Athanassios; Elvsåshagen, Torbjørn; Ferrier, I. Nicol; Fiorentino, Alessia; Foroud, Tatiana M.; Forty, Liz; Frei, Oleksandr; Freimer, Nelson B.; Frisén, Louise; Gade, Katrin; Garnham, Julie; Gelernter, Joel; Gizer, Ian R.; Gordon-Smith, Katherine; Greenwood, Tiffany A.; Guzman-Parra, José; Ha, Kyooseob; Haraldsson, Magnus; Hautzinger, Martin; Heilbronner, Urs; Hellgren, Dennis; Holmans, Peter A.; Huckins, Laura; Johnson, Jessica S.; Kalman, Janos L.; Kamatani, Yoichiro; Kittel-Schneider, Sarah; Koromina, Maria; Kranz, Thorsten M.; Kranzler, Henry R.; Kubo, Michiaki; Kupka, Ralph; Kushner, Steven A.; Lavebratt, Catharina; Leber, Markus; Lee, Heon-Jeong; Levy, Shawn E.; Lewis, Catrin; Lundberg, Martin; Magnusson, Sigurdur H.; Maihofer, Adam; Malaspina, Dolores; Maratou, Eirini; Martinsson, Lina; McGregor, Nathaniel W.; McKay, James D.; Medeiros, Helena; Millischer, Vincent; Moran, Jennifer L.; Morris, Derek W.; Mühleisen, Thomas W.; O’Brien, Niamh; O’Donovan, Claire; Olde Loohuis, Loes M.; Oruc, Lilijana; Papiol, Sergi; Pardiñas, Antonio F.; Perry, Amy; Pfennig, Andrea; Porichi, Evgenia; Raj, Towfique; Rapaport, Mark H.; DePaulo, J. Raymond; Regeer, Eline J.; Rivas, Fabio; Roth, Julian; Roussos, Panos; Ruderfer, Douglas M.; Senner, Fanny; Sharp, Sally; Shilling, Paul D.; Slaney, Claire; Sobell, Janet L.; Artigas, Maria Soler; Spijker, Anne T.; Stein, Dan J.; Terao, Chikashi; Toma, Claudio; Tooney, Paul; Tsermpini, Evangelia-Eirini; Vawter, Marquis P.; Vedder, Helmut; Xi, Simon; Xu, Wei; Kay Yang, Jessica Mei; Young, Allan H.; Young, Hannah; Zandi, Peter P.; Zhou, Hang; Psychiatry, HUNT All-In; Babadjanova, Gulja; Backlund, Lena; Bengesser, Susanne; Blackwood, Douglas H.R.; Carr, Vaughan J.; Catts, Stanley; Dikeos, Dimitris; Etain, Bruno; Ferentinos, Panagiotis; Gawlik, Micha; Gershon, Elliot S.; Henskens, Frans; Hillert, Jan; Hong, Kyung Sue; Hultman, Christina M.; Hveem, Kristian; Iwata, Nakao; Jablensky, Assen V.; Kirov, George; Lochner, Christine; Loughland, Carmel; Mathews, Carol A.; McMahon, Francis J.; Michie, Patricia; Mowry, Bryan; Neale, Benjamin M.; Nievergelt, Caroline M.; Oedegaard, Ketil J.; Olsson, Tomas; Pantelis, Chris; Patrinos, George P.; Reininghaus, Eva Z.; Saito, Takeo; Schall, Ulrich; Schalling, Martin; Scott, Rodney J.; Weickert, Cynthia Shannon; Stordal, Eystein; Vaaler, Arne E.; Vieta, Eduard; Waldman, Irwin D.; Zwart, John-Anker; Nurnberger, John I.; Stahl, Eli A.; Di Florio, Arianna; Adan, Roger A.H.; Ando, Tetsuya; Aschauer, Harald; Baker, Jessica H.; Bencko, Vladimir; Birgegård, Andreas; Boden, Joseph M.; Boehm, Ilka; Boni, Claudette; Perica, Vesna Boraska; Buehren, Katharina; Bulik, Cynthia M.; Burghardt, Roland; Carlberg, Laura; Cassina, Matteo; Clementi, Maurizio; Cone, Roger D.; Courtet, Philippe; Crowley, James J.; Danner, Unna N.; Davis, Oliver S.P.; de Zwaan, Martina; Dedoussis, George; Degortes, Daniela; DeSocio, Janiece E.; Dick, Danielle M.; Dina, Christian; Dmitrzak-Weglarz, Monika; Martinez, Elisa Docampo; Duncan, Laramie E.; Egberts, Karin; Mattingsdal, Morten; McDevitt, Sara; Meulenbelt, Ingrid; Micali, Nadia; Mitchell, James; Mitchell, Karen; Monteleone, Palmiero; Monteleone, Alessio Maria; Munn-Chernoff, Melissa A.; Nacmias, Benedetta; Navratilova, Marie; Ntalla, Ioanna; Olsen, Catherine M.; O’Toole, Julie K.; Padyukov, Leonid; Palotie, Aarno; Pantel, Jacques; Papezova, Hana; Parker, Richard; Pearson, John F.; Ehrlich, Stefan; Escaramís, Geòrgia; Espeseth, Thomas; Estivill, Xavier; Farmer, Anne; Favaro, Angela; Fischer, Krista; Floyd, James A.B.; Föcker, Manuel; Foretova, Lenka; Forzan, Monica; Franklin, Christopher S.; Gambaro, Giovanni; Giuranna, Johanna; Giusti-Rodríquez, Paola; Gonidakis, Fragiskos; Gordon, Scott; Mayora, Monica Gratacos; Guillaume, Sébastien; Hanscombe, Ken B.; Hatzikotoulas, Konstantinos; Hebebrand, Johannes; Helder, Sietske G.; Henders, Anjali K.; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Hinney, Anke; Horwood, L. John; Hübel, Christopher; Petersen, Liselotte V.; Purves, Kirstin L.; Raevuori, Anu; Reichborn-Kjennerud, Ted; Ricca, Valdo; Ripatti, Samuli; Ritschel, Franziska; Roberts, Marion; Rybakowski, Filip; Santonastaso, Paolo; Scherag, André; Schmidt, Ulrike; Schork, Nicholas J.; Schosser, Alexandra; Seitz, Jochen; Slachtova, Lenka; Slagboom, P. Eline; Slof-Op ‘t Landt, Margarita C.T.; Slopien, Agnieszka; Soranzo, Nicole; Sorbi, Sandro; Southam, Lorraine; Steen, Vidar W.; Huckins, Laura M.; Hudson, James I.; Imgart, Hartmut; Inoko, Hidetoshi; Janout, Vladimir; Jordan, Jennifer; Julià, Antonio; Kalsi, Gursharan; Kaminská, Deborah; Kaprio, Jaakko; Karhunen, Leila; Karwautz, Andreas; Kas, Martien J.H.; Kennedy, Martin A.; Keski-Rahkonen, Anna; Kiezebrink, Kirsty; Kim, Youl-Ri; Kirk, Katherine M.; Klareskog, Lars; Knudsen, Gun Peggy S.; Larsen, Janne T.; Le Hellard, Stephanie; Leppä, Virpi M.; Lichtenstein, Paul; Lin, Bochao Danae; Lundervold, Astri; Luykx, Jurjen; Maj, Mario; Mannik, Katrin; Marsal, Sara; Stuber, Garret D.; Szatkiewicz, Jin P.; Tachmazidou, Ioanna; Tenconi, Elena; Tortorella, Alfonso; Tozzi, Federica; Tsitsika, Artemis; Tyszkiewicz-Nwafor, Marta; Tziouvas, Konstantinos; van Elburg, Annemarie A.; van Furth, Eric F.; Wade, Tracey D.; Wagner, Gudrun; Walton, Esther; Whiteman, David C.; Wichmann, H. Erich; Widen, Elisabeth; Yao, Shuyang; Zeggini, Eleftheria; Zerwas, Stephanie; Zipfel, Stephan; Jungkunz, Martin; Dietl, Lydie; Schwarze, Cornelia E.; Dahmen, Norbert; Schott, Björn H.; Mobascher, Arian; Crivelli, Silvia; Dennis, Michelle F.; Harvey, Phillip D.; Carter, Bruce W.; Huffman, Jennifer E.; Jacobson, Daniel; Madduri, Ravi; Olsen, Maren K.; Pestian, John; Gaziano, J. Michael; Muralidhar, Sumitra; Ramoni, Rachel; Beckham, Jean; Chang, Kyong-Mi; O’Donnell, Christopher J.; Tsao, Philip; Breeling, James; Huang, Grant; Romero, J.P. Casas; Moser, Jennifer; Whitbourne, Stacey B.; Brewer, Jessica V.; Aslan, Mihaela; Connor, Todd; Argyres, Dean P.; Stephens, Brady; Brophy, Mary T.; Humphries, Donald E.; Selva, Luis E.; Do, Nhan; Shayan, Shahpoor; Cho, Kelly; Pyarajan, Saiju; Hauser, Elizabeth; Sun, Yan; Zhao, Hongyu; Wilson, Peter; McArdle, Rachel; Dellitalia, Louis; Mattocks, Kristin; Harley, John; Zablocki, Clement J.; Whittle, Jeffrey; Jacono, Frank; Gutierrez, Salvador; Gibson, Gretchen; Hammer, Kimberly; Kaminsky, Laurence; Villareal, Gerardo; Kinlay, Scott; Xu, Junzhe; Hamner, Mark; Mathew, Roy; Bhushan, Sujata; Iruvanti, Pran; Godschalk, Michael; Ballas, Zuhair; Ivins, Douglas; Mastorides, Stephen; Moorman, Jonathan; Gappy, Saib; Klein, Jon; Ratcliffe, Nora; Florez, Hermes; Okusaga, Olaoluwa; Murdoch, Maureen; Sriram, Peruvemba; Yeh, Shing Shing; Tandon, Neeraj; Jhala, Darshana; Aguayo, Samuel; Cohen, David; Sharma, Satish; Liangpunsakul, Suthat; Oursler, Kris Ann; Whooley, Mary; Ahuja, Sunil; Constans, Joseph; Meyer, Paul; Greco, Jennifer; Rauchman, Michael; Servatius, Richard; Gaddy, Melinda; Wallbom, Agnes; Morgan, Timothy; Stapley, Todd; Sherman, Scott; Ross, George; Tsao, Philip; Strollo, Patrick; Boyko, Edward; Meyer, Laurence; Gupta, Samir; Huq, Mostaqul; Fayad, Joseph; Hung, Adriana; Lichy, Jack; Hurley, Robin; Robey, Brooks; Striker, Robert; Erlangsen, Annette; Kessler, Ronald C.; Porteous, David; Ursano, Robert J.; Wasserman, Danuta; Coon, Hilary; Demontis, Ditte; Docherty, Anna R.; Kuo, Po-Hsiu; Mann, J. John; Rentería, Miguel E.; Stein, Murray B.; Willour, Virginia (2022)
    Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
  • Brommer, Jon; Kluen, Edward (2012)
    When several personality traits covary, they form a behavioral syndrome. Understanding the evolutionary dynamics of a behavioral syndrome requires knowledge of its genetic underpinning. At present, our understanding of the genetic basis of behavioral syndromes is largely restricted to domestic and laboratory animals. Wild behavioral syndromes are mostly inferred on the basis of phenotypic correlations, and thus make the “phenotypic gambit” of assuming that these phenotypic correlations capture the underlying genetic correlations. On the basis of 3 years of reciprocal cross-fostering of 2896 nestlings of 271 families within a pedigreed population, we show that the nestling personality traits handling aggression, breathing rate, and docility are heritable (h2 = 16–29%), and often have a pronounced “nest-of-rearing” variance component (10–15%), but a relatively small “nest-of-origin” variance component (0–7%). The three nestling personality traits form a behavioral syndrome on the phenotypic and genetic level. Overall, the phenotypic correlations provide a satisfactory description of the genetic ones, but significantly underestimate the magnitude of one of the pairwise genetic correlations, which mirrors the conclusion based on domestic and laboratory studies.
  • Int Parkinson's Dis Genomics Cons; Guerreiro, Rita; Escott-Price, Valentina; Tienari, Pentti J.; Myllykangas, Liisa; Oinas, Minna (2019)
    Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.
  • Lehtonen, Leevi (Helsingin yliopisto, 2021)
    Sex differences can be found in most human phenotypes, and they play an important role in human health and disease. Females and males have different sex chromosomes, which are known to cause sex differences, as are differences in the concentration of sex hormones such as testosterone, estradiol and progesterone. However, the role of the autosomes has remained more debated. The primary aim of this thesis is to assess the magnitude and relevance of human sex-specific genetic architecture in the autosomes. This is done by calculating sex-specific heritability estimates and genetic correlation estimates between females and males, as well as comparing these to sex differences on the phenotype level. Additionally, the heritability and genetic correlation estimates are compared between two populations, in order to assess the magnitude of sex differences compared to differences between populations. The analyses in this thesis are based on sex-stratified genome-wide association study (GWAS) data from 48 phenotypes in the UK Biobank (UKB), which contains genotype data from approximately 500 000 individuals as well as thousands of phenotype measurements. A replication of the analyses using three phenotypes was also made on data from the FinnGen project, with a dataset from approximately 175 000 individuals. The 48 phenotypes used in this study range from biomarkers such as serum testosterone and albumin levels to general traits such as height and blood pressure. The heritability and genetic correlation estimates were calculated using linkage disequilibrium score regression (LDSC). LDSC fits a linear regression model between test statistic values of GWAS variants and linkage disequilibrium (LD) scores calculated from a reference population. For most phenotypes, the heritability and genetic correlation results show little evidence of sex differences. Serum testosterone level and waist-to-hip ratio are exceptions to this, showing strong evidence of sex differences both on the genetic and the phenotype level. However, the overall correlation between phenotype level sex differences and sex differences in heritability or genetic correlation estimates is low. The replication in the FinnGen dataset for height, weight and body mass index (BMI), showed that for these traits the differences in heritability estimates and genetic correlations between the Finnish and UK populations are comparable or larger than the differences found between males and females.