Person: Westra, Harm-Jan
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Westra
First Name
Harm-Jan
Name
Westra, Harm-Jan
10 results
Search Results
Now showing 1 - 10 of 10
Publication The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study(Public Library of Science, 2015) Winkler, Thomas W.; Justice, Anne E.; Graff, Mariaelisa; Barata, Llilda; Feitosa, Mary F.; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove; Kilpeläinen, Tuomas O.; Lu, Yingchang; Mägi, Reedik; Mihailov, Evelin; Pers, Tune H; Rüeger, Sina; Teumer, Alexander; Ehret, Georg B.; Ferreira, Teresa; Heard-Costa, Nancy L.; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D.; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M.; Jansen, Rick; Westra, Harm-Jan; White, Charles C.; Absher, Devin; Ahluwalia, Tarunveer S.; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L.; de Craen, Anton J. M.; Bis, Joshua C.; Bonnefond, Amélie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W. K.; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E.; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B.; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jackson, Anne U.; Jacobs, Kevin B.; Johansson, Åsa; Kaakinen, Marika; Kleber, Marcus E.; Lahti, Jari; Leach, Irene Mateo; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A. F.; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L.; Montasser, May E.; Müller, Gabriele; Müller-Nurasyid, Martina; Nolte, Ilja M.; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W.; Renström, Frida; Rizzi, Federica; Rose, Lynda M.; Ryan, Kathy A.; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stančáková, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J.; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P.; Vandenput, Liesbeth; van der Laan, Sander W; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L.; Wang, Sophie R.; Wang, Zhaoming; Wild, Sarah H.; Willenborg, Christina; Wilson, James F.; Wong, Andrew; Yang, Jian; Yengo, Loïc; Yerges-Armstrong, Laura M.; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A.; Bakker, Stephan J. L.; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blüher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L.; Boyd, Heather A.; Bruinenberg, Marcel; Buchman, Aron S; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S.; Claudi-Boehm, Simone; Cole, John; Collins, Francis S.; de Geus, Eco J. C.; de Groot, Lisette C. P. G. M.; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G.; Friedrich, Nele; Gejman, Pablo V.; Gigante, Bruna; Glorioso, Nicola; Go, Alan S.; Gottesman, Omri; Gräßler, Jürgen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C.; Hansen, Torben; Harris, Tamara B.; Hartman, Catharina A.; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T.; Heath, Andrew C.; Henders, Anjali K.; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G; Hui, Jennie; Husemoen, Lise L.; Hutri-Kähönen, Nina; Hysi, Pirro G.; Illig, Thomas; De Jager, Philip; Jalilzadeh, Shapour; Jørgensen, Torben; Jukema, J. Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J.; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T.; Kratzer, Wolfgang; Krüger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J.; Leander, Karin; Lindström, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stéphane; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Magnusson, Patrik K.; McArdle, Wendy L.; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W.; Morris, Andrew P.; Narisu, Narisu; Nelis, Mari; Ong, Ken K.; Palotie, Aarno; Pérusse, Louis; Pichler, Irene; Pilia, Maria G.; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M.; Rice, Treva K.; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R.; Sarzynski, Mark A.; Scholtens, Salome; Scott, Robert A.; Scott, William R.; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P. Eline; Smit, Jan H.; Sparsø, Thomas H.; Stirrups, Kathleen; Stolk, Ronald P.; Stringham, Heather M.; Swertz, Morris A; Swift, Amy J.; Syvänen, Ann-Christine; Tan, Sian-Tsung; Thorand, Barbara; Tönjes, Anke; Tremblay, Angelo; Tsafantakis, Emmanouil; van der Most, Peter J.; Völker, Uwe; Vohl, Marie-Claude; Vonk, Judith M.; Waldenberger, Melanie; Walker, Ryan W.; Wennauer, Roman; Widén, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Wright, Alan F.; Zillikens, M. Carola; van Dijk, Suzanne C.; van Schoor, Natasja M.; Asselbergs, Folkert W.; de Bakker, Paul I. W.; Beckmann, Jacques S.; Beilby, John; Bennett, David A.; Bergman, Richard N.; Bergmann, Sven; Böger, Carsten A.; Boehm, Bernhard O.; Boerwinkle, Eric; Boomsma, Dorret I.; Bornstein, Stefan R.; Bottinger, Erwin P.; Bouchard, Claude; Chambers, John C.; Chanock, Stephen J.; Chasman, Daniel; Cucca, Francesco; Cusi, Daniele; Dedoussis, George; Erdmann, Jeanette; Eriksson, Johan G.; Evans, Denis A.; de Faire, Ulf; Farrall, Martin; Ferrucci, Luigi; Ford, Ian; Franke, Lude; Franks, Paul; Froguel, Philippe; Gansevoort, Ron T.; Gieger, Christian; Grönberg, Henrik; Gudnason, Vilmundur; Gyllensten, Ulf; Hall, Per; Hamsten, Anders; van der Harst, Pim; Hayward, Caroline; Heliövaara, Markku; Hengstenberg, Christian; Hicks, Andrew A; Hingorani, Aroon; Hofman, Albert; Hu, Frank; Huikuri, Heikki V.; Hveem, Kristian; James, Alan L.; Jordan, Joanne M.; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Kathiresan, Sekar; Kiemeney, Lambertus A. L. M.; Kivimaki, Mika; Knekt, Paul B.; Koistinen, Heikki A.; Kooner, Jaspal S.; Koskinen, Seppo; Kuusisto, Johanna; Maerz, Winfried; Martin, Nicholas G; Laakso, Markku; Lakka, Timo A.; Lehtimäki, Terho; Lettre, Guillaume; Levinson, Douglas F.; Lind, Lars; Lokki, Marja-Liisa; Mäntyselkä, Pekka; Melbye, Mads; Metspalu, Andres; Mitchell, Braxton D.; Moll, Frans L.; Murray, Jeffrey C.; Musk, Arthur W.; Nieminen, Markku S.; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Oostra, Ben A.; Palmer, Lyle J; Pankow, James S.; Pasterkamp, Gerard; Pedersen, Nancy L.; Pedersen, Oluf; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Polašek, Ozren; Pramstaller, Peter P.; Psaty, Bruce M.; Qi, Lu; Quertermous, Thomas; Raitakari, Olli T.; Rankinen, Tuomo; Rauramaa, Rainer; Ridker, Paul; Rioux, John D.; Rivadeneira, Fernando; Rotter, Jerome I.; Rudan, Igor; den Ruijter, Hester M.; Saltevo, Juha; Sattar, Naveed; Schunkert, Heribert; Schwarz, Peter E. H.; Shuldiner, Alan R.; Sinisalo, Juha; Snieder, Harold; Sørensen, Thorkild I. A.; Spector, Tim D.; Staessen, Jan A.; Stefania, Bandinelli; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tardif, Jean-Claude; Tremoli, Elena; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; Verbeek, André L. M.; Vermeulen, Sita H.; Viikari, Jorma S.; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Waeber, Gérard; Walker, Mark; Wallaschofski, Henri; Wareham, Nicholas J.; Watkins, Hugh; Zeggini, Eleftheria; Chakravarti, Aravinda; Clegg, Deborah J.; Cupples, L. Adrienne; Gordon-Larsen, Penny; Jaquish, Cashell E.; Rao, D. C.; Abecasis, Goncalo R.; Assimes, Themistocles L.; Barroso, Inês; Berndt, Sonja I.; Boehnke, Michael; Deloukas, Panos; Fox, Caroline; Groop, Leif C.; Hunter, David; Ingelsson, Erik; Kaplan, Robert C.; McCarthy, Mark I.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Schlessinger, David; Strachan, David P.; Stefansson, Kari; van Duijn, Cornelia M.; Hirschhorn, Joel; Lindgren, Cecilia M.; Heid, Iris M.; North, Kari E.; Borecki, Ingrid B.; Kutalik, Zoltán; Loos, Ruth J. F.Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Publication The transcriptional landscape of age in human peripheral blood(Nature Pub. Group, 2015) Peters, Marjolein J.; Joehanes, Roby; Pilling, Luke C.; Schurmann, Claudia; Conneely, Karen N.; Powell, Joseph; Reinmaa, Eva; Sutphin, George L.; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A.; Kobes, Sayuko; Tukiainen, Taru; Nalls, Michael A.; Hernandez, Dena G.; Cookson, Mark R.; Gibbs, Raphael J.; Hardy, John; Ramasamy, Adaikalavan; Zonderman, Alan B.; Dillman, Allissa; Traynor, Bryan; Smith, Colin; Longo, Dan L.; Trabzuni, Daniah; Troncoso, Juan; van der Brug, Marcel; Weale, Michael E.; O'Brien, Richard; Johnson, Robert; Walker, Robert; Zielke, Ronald H.; Arepalli, Sampath; Ryten, Mina; Singleton, Andrew B.; Ramos, Yolande F.; Göring, Harald H. H.; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A.; Stranger, Barbara E.; De Jager, Philip; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M.; Munson, Peter J.; Huan, Tianxiao; Hofman, Albert; Uitterlinden, André G.; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M. P. J.; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J.; Peterson, Pärt; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K.; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Illig, Thomas; Homuth, Georg; Grabe, Hans-Jörgen; Völzke, Henry; Steil, Leif; Kocher, Thomas; Murray, Anna; Melzer, David; Yaghootkar, Hanieh; Bandinelli, Stefania; Moses, Eric K.; Kent, Jack W.; Curran, Joanne E.; Johnson, Matthew P.; Williams-Blangero, Sarah; Westra, Harm-Jan; McRae, Allan F.; Smith, Jennifer A.; Kardia, Sharon L. R.; Hovatta, Iiris; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Henders, Anjali K.; Martin, Nicholas G.; Smith, Alicia K.; Mehta, Divya; Binder, Elisabeth B.; Nylocks, K Maria; Kennedy, Elizabeth M.; Klengel, Torsten; Ding, Jingzhong; Suchy-Dicey, Astrid M.; Enquobahrie, Daniel A.; Brody, Jennifer; Rotter, Jerome I.; Chen, Yii-Der I.; Houwing-Duistermaat, Jeanine; Kloppenburg, Margreet; Slagboom, P. Eline; Helmer, Quinta; den Hollander, Wouter; Bean, Shannon; Raj, Towfique; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J.; Psaty, Bruce M.; Tracy, Russell P.; Montgomery, Grant W.; Turner, Stephen T.; Blangero, John; Meulenbelt, Ingrid; Ressler, Kerry J.; Yang, Jian; Franke, Lude; Kettunen, Johannes; Visscher, Peter M.; Neely, G. Gregory; Korstanje, Ron; Hanson, Robert L.; Prokisch, Holger; Ferrucci, Luigi; Esko, Tõnu; Teumer, Alexander; van Meurs, Joyce B. J.; Johnson, Andrew D.Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the ‘transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.Publication GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment(American Association for the Advancement of Science (AAAS), 2013) Rietveld, Cornelius A.; Medland, Sarah E.; Derringer, Jaime; Yang, Jian; Esko, Tõnu; Martin, Nicolas W.; Westra, Harm-Jan; Shakhbazov, Konstantin; Abdellaoui, Abdel; Agrawal, Arpana; Albrecht, Eva; Alizadeh, Behrooz Z.; Amin, Najaf; Barnard, John; Baumeister, Sebastian E.; Benke, Kelly S.; Bielak, Lawrence F.; Boatman, Jeffrey A.; Boyle, Patricia A.; Davies, Gail; de Leeuw, Christiaan; Eklund, Niina; Evans, Daniel S.; Ferhmann, Rudolf; Fischer, Krista; Gieger, Christian; Gjessing, Håkon K.; Hagg, Sara; Harris, Jennifer R.; Hayward, Caroline; Holzapfel, Christina; Ibrahim-Verbaas, Carla A.; Ingelsson, Erik; Jacobsson, Bo; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika; Kanoni, Stavroula; Karjalainen, Juha; Kolcic, Ivana; Kristiansson, Kati; Kutalik, Zoltán; Lahti, Jari; Lee, Sang H.; Lin, Peng; Lind, Penelope A.; Liu, Yongmei; Lohman, Kurt; Loitfelder, Marisa; McMahon, George; Vidal, Pedro Marques; Meirelles, Osorio; Milani, Lili; Myhre, Ronny; Nuotio, Marja-Liisa; Oldmeadow, Christopher J.; Petrovic, Katja E.; Peyrot, Wouter J.; Polašek, Ozren; Quaye, Lydia; Reinmaa, Eva; Rice, John P.; Rizzi, Thais S.; Schmidt, Helena; Schmidt, Reinhold; Smith, Albert V.; Smith, Jennifer A.; Tanaka, Toshiko; Terracciano, Antonio; van der Loos, Matthijs J. H. M.; Vitart, Veronique; Völzke, Henry; Wellmann, Jürgen; Yu, Lei; Zhao, Wei; Allik, Jüri; Attia, John R.; Bandinelli, Stefania; Bastardot, François; Beauchamp, Jonathan; Bennett, David A.; Berger, Klaus; Bierut, Laura J.; Boomsma, Dorret I.; Bültmann, Ute; Campbell, Harry; Chabris, Christopher; Cherkas, Lynn; Chung, Mina K.; Cucca, Francesco; de Andrade, Mariza; De Jager, Philip; De Neve, Jan-Emmanuel; Deary, Ian J.; Dedoussis, George V.; Deloukas, Panos; Dimitriou, Maria; Eiríksdóttir, Guðný; Elderson, Martin F.; Eriksson, Johan G.; Evans, David M.; Faul, Jessica D.; Ferrucci, Luigi; Garcia, Melissa E.; Grönberg, Henrik; Guðnason, Vilmundur; Hall, Per; Harris, Juliette M.; Harris, Tamara B.; Hastie, Nicholas D.; Heath, Andrew C.; Hernandez, Dena G.; Hoffmann, Wolfgang; Hofman, Adriaan; Holle, Rolf; Holliday, Elizabeth G.; Hottenga, Jouke-Jan; Iacono, William G.; Illig, Thomas; Järvelin, Marjo-Riitta; Kähönen, Mika; Kaprio, Jaakko; Kirkpatrick, Robert M.; Kowgier, Matthew; Latvala, Antti; Launer, Lenore J.; Lawlor, Debbie A.; Lehtimäki, Terho; Li, Jingmei; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C.; Madden, Pamela A.; Magnusson, Patrik K. E.; Makinen, Tomi E.; Masala, Marco; McGue, Matt; Metspalu, Andres; Mielck, Andreas; Miller, Michael B.; Montgomery, Grant W.; Mukherjee, Sutapa; Nyholt, Dale R.; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Penninx, Brenda W. J. H.; Perola, Markus; Peyser, Patricia A.; Preisig, Martin; Räikkönen, Katri; Raitakari, Olli T.; Realo, Anu; Ring, Susan M.; Ripatti, Samuli; Rivadeneira, Fernando; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sarin, Antti-Pekka; Schlessinger, David; Scott, Rodney J.; Snieder, Harold; St Pourcain, Beate; Starr, John M.; Sul, Jae; Surakka, Ida; Svento, Rauli; Teumer, Alexander; Tiemeier, Henning; van Rooij, Frank J. A.; Van Wagoner, David R.; Vartiainen, Erkki; Viikari, Jorma; Vollenweider, Peter; Vonk, Judith M.; Waeber, Gérard; Weir, David R.; Wichmann, H.-Erich; Widen, Elisabeth; Willemsen, Gonneke; Wilson, James F.; Wright, Alan F.; Conley, Dalton; Davey-Smith, George; Franke, Lude; Groenen, Patrick J. F.; Hofman, Albert; Johannesson, Magnus; Kardia, Sharon L. R.; Krueger, Robert F.; Laibson, David; Martin, Nicholas G.; Meyer, Michelle N.; Posthuma, Danielle; Thurik, A. Roy; Timpson, Nicholas J.; Uitterlinden, André G.; van Duijn, Cornelia M.; Visscher, Peter M.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R2 ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.Publication Pathogenic implications for autoimmune mechanisms derived by comparative eQTL analysis of CD4+ versus CD8+ T cells(Public Library of Science, 2017) Kasela, Silva; Kisand, Kai; Tserel, Liina; Kaleviste, Epp; Remm, Anu; Fischer, Krista; Esko, Tõnu; Westra, Harm-Jan; Fairfax, Benjamin P.; Makino, Seiko; Knight, Julian C.; Franke, Lude; Metspalu, Andres; Peterson, Pärt; Milani, LiliInappropriate activation or inadequate regulation of CD4+ and CD8+ T cells may contribute to the initiation and progression of multiple autoimmune and inflammatory diseases. Studies on disease-associated genetic polymorphisms have highlighted the importance of biological context for many regulatory variants, which is particularly relevant in understanding the genetic regulation of the immune system and its cellular phenotypes. Here we show cell type-specific regulation of transcript levels of genes associated with several autoimmune diseases in CD4+ and CD8+ T cells including a trans-acting regulatory locus at chr12q13.2 containing the rs1131017 SNP in the RPS26 gene. Most remarkably, we identify a common missense variant in IL27, associated with type 1 diabetes that results in decreased functional activity of the protein and reduced expression levels of downstream IRF1 and STAT1 in CD4+ T cells only. Altogether, our results indicate that eQTL mapping in purified T cells provides novel functional insights into polymorphisms and pathways associated with autoimmune diseases.Publication New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk(Nature Publishing Group, 2016) Lu, Yingchang; Day, Felix R.; Gustafsson, Stefan; Buchkovich, Martin L.; Na, Jianbo; Bataille, Veronique; Cousminer, Diana L.; Dastani, Zari; Drong, Alexander W.; Esko, Tõnu; Evans, David M.; Falchi, Mario; Feitosa, Mary F.; Ferreira, Teresa; Hedman, Åsa K.; Haring, Robin; Hysi, Pirro G.; Iles, Mark M.; Justice, Anne E.; Kanoni, Stavroula; Lagou, Vasiliki; Li, Rui; Li, Xin; Locke, Adam; Lu, Chen; Mägi, Reedik; Perry, John R. B.; Pers, Tune H; Qi, Qibin; Sanna, Marianna; Schmidt, Ellen M.; Scott, William R.; Shungin, Dmitry; Teumer, Alexander; Vinkhuyzen, Anna A. E.; Walker, Ryan W.; Westra, Harm-Jan; Zhang, Mingfeng; Zhang, Weihua; Zhao, Jing Hua; Zhu, Zhihong; Afzal, Uzma; Ahluwalia, Tarunveer Singh; Bakker, Stephan J. L.; Bellis, Claire; Bonnefond, Amélie; Borodulin, Katja; Buchman, Aron S.; Cederholm, Tommy; Choh, Audrey C.; Choi, Hyung Jin; Curran, Joanne E.; de Groot, Lisette C. P. G. M.; De Jager, Philip; Dhonukshe-Rutten, Rosalie A. M.; Enneman, Anke W.; Eury, Elodie; Evans, Daniel S.; Forsen, Tom; Friedrich, Nele; Fumeron, Frédéric; Garcia, Melissa E.; Gärtner, Simone; Han, Bok-Ghee; Havulinna, Aki S.; Hayward, Caroline; Hernandez, Dena; Hillege, Hans; Ittermann, Till; Kent, Jack W.; Kolcic, Ivana; Laatikainen, Tiina; Lahti, Jari; Leach, Irene Mateo; Lee, Christine G.; Lee, Jong-Young; Liu, Tian; Liu, Youfang; Lobbens, Stéphane; Loh, Marie; Lyytikäinen, Leo-Pekka; Medina-Gomez, Carolina; Michaëlsson, Karl; Nalls, Mike A.; Nielson, Carrie M.; Oozageer, Laticia; Pascoe, Laura; Paternoster, Lavinia; Polašek, Ozren; Ripatti, Samuli; Sarzynski, Mark A.; Shin, Chan Soo; Narančić, Nina Smolej; Spira, Dominik; Srikanth, Priya; Steinhagen-Thiessen, Elisabeth; Sung, Yun Ju; Swart, Karin M. A.; Taittonen, Leena; Tanaka, Toshiko; Tikkanen, Emmi; van der Velde, Nathalie; van Schoor, Natasja M.; Verweij, Niek; Wright, Alan F.; Yu, Lei; Zmuda, Joseph M.; Eklund, Niina; Forrester, Terrence; Grarup, Niels; Jackson, Anne U.; Kristiansson, Kati; Kuulasmaa, Teemu; Kuusisto, Johanna; Lichtner, Peter; Luan, Jian'an; Mahajan, Anubha; Männistö, Satu; Palmer, Cameron D.; Ried, Janina S.; Scott, Robert A.; Stancáková, Alena; Wagner, Peter J.; Demirkan, Ayse; Döring, Angela; Gudnason, Vilmundur; Kiel, Douglas; Kühnel, Brigitte; Mangino, Massimo; Mcknight, Barbara; Menni, Cristina; O'Connell, Jeffrey R.; Oostra, Ben A.; Shuldiner, Alan R.; Song, Kijoung; Vandenput, Liesbeth; van Duijn, Cornelia M.; Vollenweider, Peter; White, Charles C.; Boehnke, Michael; Boettcher, Yvonne; Cooper, Richard S.; Forouhi, Nita G.; Gieger, Christian; Grallert, Harald; Hingorani, Aroon; Jørgensen, Torben; Jousilahti, Pekka; Kivimaki, Mika; Kumari, Meena; Laakso, Markku; Langenberg, Claudia; Linneberg, Allan; Luke, Amy; Mckenzie, Colin A.; Palotie, Aarno; Pedersen, Oluf; Peters, Annette; Strauch, Konstantin; Tayo, Bamidele O.; Wareham, Nicholas J.; Bennett, David A.; Bertram, Lars; Blangero, John; Blüher, Matthias; Bouchard, Claude; Campbell, Harry; Cho, Nam H.; Cummings, Steven R.; Czerwinski, Stefan A.; Demuth, Ilja; Eckardt, Rahel; Eriksson, Johan G.; Ferrucci, Luigi; Franco, Oscar H.; Froguel, Philippe; Gansevoort, Ron T.; Hansen, Torben; Harris, Tamara B.; Hastie, Nicholas; Heliövaara, Markku; Hofman, Albert; Jordan, Joanne M.; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Knekt, Paul B.; Koskinen, Seppo; Kovacs, Peter; Lehtimäki, Terho; Lind, Lars; Liu, Yongmei; Orwoll, Eric S.; Osmond, Clive; Perola, Markus; Pérusse, Louis; Raitakari, Olli T.; Rankinen, Tuomo; Rao, D. C.; Rice, Treva K.; Rivadeneira, Fernando; Rudan, Igor; Salomaa, Veikko; Sørensen, Thorkild I. A.; Stumvoll, Michael; Tönjes, Anke; Towne, Bradford; Tranah, Gregory J.; Tremblay, Angelo; Uitterlinden, André G.; van der Harst, Pim; Vartiainen, Erkki; Viikari, Jorma S.; Vitart, Veronique; Vohl, Marie-Claude; Völzke, Henry; Walker, Mark; Wallaschofski, Henri; Wild, Sarah; Wilson, James F.; Yengo, Loïc; Bishop, D. Timothy; Borecki, Ingrid B.; Chambers, John C.; Cupples, L. Adrienne; Dehghan, Abbas; Deloukas, Panos; Fatemifar, Ghazaleh; Fox, Caroline; Furey, Terrence S.; Franke, Lude; Han, Jiali; Hunter, David; Karjalainen, Juha; Karpe, Fredrik; Kaplan, Robert C.; Kooner, Jaspal S.; McCarthy, Mark I.; Murabito, Joanne M.; Morris, Andrew P.; Bishop, Julia A. N.; North, Kari E.; Ohlsson, Claes; Ong, Ken K.; Prokopenko, Inga; Richards, J. Brent; Schadt, Eric E.; Spector, Tim D.; Widén, Elisabeth; Willer, Cristen J.; Yang, Jian; Ingelsson, Erik; Mohlke, Karen L.; Hirschhorn, Joel; Pospisilik, John Andrew; Zillikens, M. Carola; Lindgren, Cecilia; Kilpeläinen, Tuomas Oskari; Loos, Ruth J. F.To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.Publication Genetic variants associated with subjective well-being, depressive symptoms and neuroticism identified through genome-wide analyses(2016) Okbay, Aysu; Baselmans, Bart M.L.; De Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel G.; Fontana, Mark Alan; Meddens, S. Fleur W.; Linnér, Richard Karlsson; Rietveld, Cornelius A.; Derringer, Jaime; Gratten, Jacob; Lee, James J.; Liu, Jimmy Z.; de Vlaming, Ronald; Ahluwalia, Tarunveer S.; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C.; Furlotte, Nicholas A.; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R.; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W.; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J.; Lind, Penelope A.; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Miller, Michael B.; Minica, Camelia C.; Nolte, Ilja M.; Mook-Kanamori, Dennis; van der Most, Peter J.; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V.; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M.; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Boyle, Patricia A.; Cherney, Samantha; Cox, Simon R.; Davies, Gail; Davis, Oliver S.P.; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T.; Fatemifar, Ghazaleh; Faul, Jessica D.; Ferrucci, Luigi; Forstner, Andreas; Gieger, Christian; Gupta, Richa; Harris, Tamara B.; Harris, Juliette M.; Holliday, Elizabeth G.; Hottenga, Jouke-Jan; De Jager, Philip; Kaakinen, Marika A.; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J.; Franke, Lude; Li-Gao, Ruifang; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W.; Mosing, Miriam A.; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E.; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J.; Smith, Jennifer A.; Sutin, Angelina R.; Trzaskowski, Maciej; Vinkhuyzen, Anna E.; Yu, Lei; Zabaneh, Delilah; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I.; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J.; van Duijn, Cornelia M.; Eriksson, Johan G.; Bültmann, Ute; de Geus, Eco J.C.; Groenen, Patrick J.F.; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A.; Haworth, Claire M.A.; Hayward, Caroline; Heath, Andrew C.; Hinds, David A.; Hyppönen, Elina; Iacono, William G.; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L.R.; Keltikangas-Järvinen, Liisa; Kraft, Phillip; Kubzansky, Laura; Lehtimäki, Terho; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J.; Pasterkamp, Gerard; Pedersen, Nancy L.; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S.; Rosendaal, Frits R.; den Ruijter, Hester M.; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z.; Sørensen, Thorkild I.A.; Spector, Tim D.; Steptoe, Andrew; Terracciano, Antonio; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Uitterlinden, André G.; Vollenweider, Peter; Wagner, Gert G.; Weir, David R.; Yang, Jian; Conley, Dalton C.; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David; Medland, Sarah E.; Meyer, Michelle N.; Pickrell, Joseph K.; Esko, Tõnu; Krueger, Robert F.; Beauchamp, Jonathan P.; Koellinger, Philipp D.; Benjamin, Daniel J.; Bartels, Meike; Cesarini, DavidWe conducted genome-wide association studies of three phenotypes: subjective well-being (N = 298,420), depressive symptoms (N = 161,460), and neuroticism (N = 170,910). We identified three variants associated with subjective well-being, two with depressive symptoms, and eleven with neuroticism, including two inversion polymorphisms. The two depressive symptoms loci replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ̂| ≈ 0.8) strengthen the overall credibility of the findings, and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal/pancreas tissues are strongly enriched for association.Publication An integrative systems genetics approach reveals potential causal genes and pathways related to obesity(BioMed Central, 2015) Kogelman, Lisette J. A.; Zhernakova, Daria V.; Westra, Harm-Jan; Cirera, Susanna; Fredholm, Merete; Franke, Lude; Kadarmideen, Haja N.Background: Obesity is a multi-factorial health problem in which genetic factors play an important role. Limited results have been obtained in single-gene studies using either genomic or transcriptomic data. RNA sequencing technology has shown its potential in gaining accurate knowledge about the transcriptome, and may reveal novel genes affecting complex diseases. Integration of genomic and transcriptomic variation (expression quantitative trait loci [eQTL] mapping) has identified causal variants that affect complex diseases. We integrated transcriptomic data from adipose tissue and genomic data from a porcine model to investigate the mechanisms involved in obesity using a systems genetics approach. Methods: Using a selective gene expression profiling approach, we selected 36 animals based on a previously created genomic Obesity Index for RNA sequencing of subcutaneous adipose tissue. Differential expression analysis was performed using the Obesity Index as a continuous variable in a linear model. eQTL mapping was then performed to integrate 60 K porcine SNP chip data with the RNA sequencing data. Results were restricted based on genome-wide significant single nucleotide polymorphisms, detected differentially expressed genes, and previously detected co-expressed gene modules. Further data integration was performed by detecting co-expression patterns among eQTLs and integration with protein data. Results: Differential expression analysis of RNA sequencing data revealed 458 differentially expressed genes. The eQTL mapping resulted in 987 cis-eQTLs and 73 trans-eQTLs (false discovery rate < 0.05), of which the cis-eQTLs were associated with metabolic pathways. We reduced the eQTL search space by focusing on differentially expressed and co-expressed genes and disease-associated single nucleotide polymorphisms to detect obesity-related genes and pathways. Building a co-expression network using eQTLs resulted in the detection of a module strongly associated with lipid pathways. Furthermore, we detected several obesity candidate genes, for example, ENPP1, CTSL, and ABHD12B. Conclusions: To our knowledge, this is the first study to perform an integrated genomics and transcriptomics (eQTL) study using, and modeling, genomic and subcutaneous adipose tissue RNA sequencing data on obesity in a porcine model. We detected several pathways and potential causal genes for obesity. Further validation and investigation may reveal their exact function and association with obesity. Electronic supplementary material The online version of this article (doi:10.1186/s13073-015-0229-0) contains supplementary material, which is available to authorized users.Publication Genome-wide association study identifies 74 loci associated with educational attainment(2016) Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark A.; Lee, James J.; Pers, Tune H; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Börge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bønnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans68, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldórsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; De Jager, Philip; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kähönen, Mika; Kanoni, Stavroula; Keltigangas-Järvinen, Liisa; Kiemeney, Lambertus A.L.M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Maël P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C.M.; Loukola, Anu; Madden, Pamela A.; Mägi, Reedik; Mäki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E.R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Räikkönen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J.A.; Venturini, Cristina; Vinkhuyzen, Anna A.E.; Völker, Uwe; Völzke, Henry; Vonk, Judith M.; Vozzi, Diego; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jörgen; Gratten, Jacob; Groenen, Patrick J.F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppönen, Elina; Iacono, William G.; Jacobsson, Bo; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L.R.; Lehtimäki, Terho; Lehrer, Steven F.; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W.J.H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sørensen, Thorkild I.A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, André G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tõnu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.Summary Educational attainment (EA) is strongly influenced by social and other environmental factors, but genetic factors are also estimated to account for at least 20% of the variation across individuals1. We report the results of a genome-wide association study (GWAS) for EA that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication in an independent sample of 111,349 individuals from the UK Biobank. We now identify 74 genome-wide significant loci associated with number of years of schooling completed. Single-nucleotide polymorphisms (SNPs) associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioral phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because EA is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric disease.Publication reGenotyper: Detecting mislabeled samples in genetic data(Public Library of Science, 2017) Zych, Konrad; Snoek, Basten L.; Elvin, Mark; Rodriguez, Miriam; Van der Velde, K. Joeri; Arends, Danny; Westra, Harm-Jan; Swertz, Morris A.; Poulin, Gino; Kammenga, Jan E.; Breitling, Rainer; Jansen, Ritsert C.; Li, YangIn high-throughput molecular profiling studies, genotype labels can be wrongly assigned at various experimental steps; the resulting mislabeled samples seriously reduce the power to detect the genetic basis of phenotypic variation. We have developed an approach to detect potential mislabeling, recover the “ideal” genotype and identify “best-matched” labels for mislabeled samples. On average, we identified 4% of samples as mislabeled in eight published datasets, highlighting the necessity of applying a “data cleaning” step before standard data analysis.Publication Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci(2016) Ellinghaus, David; Jostins, Luke; Spain, Sarah L; Cortes, Adrian; Bethune, Jörn; Han, Buhm; Park, Yu Rang; Raychaudhuri, Soumya; Pouget, Jennie G; Hübenthal, Matthias; Folseraas, Trine; Wang, Yunpeng; Esko, Tonu; Metspalu, Andres; Westra, Harm-Jan; Franke, Lude; Pers, Tune H; Weersma, Rinse K; Collij, Valerie; D'Amato, Mauro; Halfvarson, Jonas; Jensen, Anders Boeck; Lieb, Wolfgang; Degenhardt, Franziska; Forstner, Andreas J; Hofmann, Andrea; Schreiber, Stefan; Mrowietz, Ulrich; Juran, Brian D; Lazaridis, Konstantinos N; Brunak, Søren; Dale, Anders M; Trembath, Richard C; Weidinger, Stephan; Weichenthal, Michael; Ellinghaus, Eva; Elder, James T; Barker, Jonathan NWN; Andreassen, Ole A; McGovern, Dermot P; Karlsen, Tom H; Barrett, Jeffrey C; Parkes, Miles; Brown, Matthew A; Franke, AndreWe simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European-ancestry we identified 244 independent multi-disease signals including 27 novel genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multi-disease signals with expression data sets from human, rat and mouse, and epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases that is genetically identical to another disease, possibly due to diagnostic misclassification, molecular subtypes, or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.