@article {8304, title = {Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.}, journal = {Nat Commun}, volume = {7}, year = {2016}, month = {2016}, pages = {10023}, abstract = {

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

}, keywords = {Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Renal Insufficiency, Chronic}, issn = {2041-1723}, doi = {10.1038/ncomms10023}, author = {Pattaro, Cristian and Teumer, Alexander and Gorski, Mathias and Chu, Audrey Y and Li, Man and Mijatovic, Vladan and Garnaas, Maija and Tin, Adrienne and Sorice, Rossella and Li, Yong and Taliun, Daniel and Olden, Matthias and Foster, Meredith and Yang, Qiong and Chen, Ming-Huei and Pers, Tune H and Johnson, Andrew D and Ko, Yi-An and Fuchsberger, Christian and Tayo, Bamidele and Nalls, Michael and Feitosa, Mary F and Isaacs, Aaron and Dehghan, Abbas and d{\textquoteright}Adamo, Pio and Adeyemo, Adebowale and Dieffenbach, Aida Karina and Zonderman, Alan B and Nolte, Ilja M and van der Most, Peter J and Wright, Alan F and Shuldiner, Alan R and Morrison, Alanna C and Hofman, Albert and Smith, Albert V and Dreisbach, Albert W and Franke, Andre and Uitterlinden, Andr{\'e} G and Metspalu, Andres and T{\"o}njes, Anke and Lupo, Antonio and Robino, Antonietta and Johansson, {\r A}sa and Demirkan, Ayse and Kollerits, Barbara and Freedman, Barry I and Ponte, Belen and Oostra, Ben A and Paulweber, Bernhard and Kr{\"a}mer, Bernhard K and Mitchell, Braxton D and Buckley, Brendan M and Peralta, Carmen A and Hayward, Caroline and Helmer, Catherine and Rotimi, Charles N and Shaffer, Christian M and M{\"u}ller, Christian and Sala, Cinzia and van Duijn, Cornelia M and Saint-Pierre, Aude and Ackermann, Daniel and Shriner, Daniel and Ruggiero, Daniela and Toniolo, Daniela and Lu, Yingchang and Cusi, Daniele and Czamara, Darina and Ellinghaus, David and Siscovick, David S and Ruderfer, Douglas and Gieger, Christian and Grallert, Harald and Rochtchina, Elena and Atkinson, Elizabeth J and Holliday, Elizabeth G and Boerwinkle, Eric and Salvi, Erika and Bottinger, Erwin P and Murgia, Federico and Rivadeneira, Fernando and Ernst, Florian and Kronenberg, Florian and Hu, Frank B and Navis, Gerjan J and Curhan, Gary C and Ehret, George B and Homuth, Georg and Coassin, Stefan and Thun, Gian-Andri and Pistis, Giorgio and Gambaro, Giovanni and Malerba, Giovanni and Montgomery, Grant W and Eiriksdottir, Gudny and Jacobs, Gunnar and Li, Guo and Wichmann, H-Erich and Campbell, Harry and Schmidt, Helena and Wallaschofski, Henri and V{\"o}lzke, Henry and Brenner, Hermann and Kroemer, Heyo K and Kramer, Holly and Lin, Honghuang and Leach, I Mateo and Ford, Ian and Guessous, Idris and Rudan, Igor and Prokopenko, Inga and Borecki, Ingrid and Heid, Iris M and Kolcic, Ivana and Persico, Ivana and Jukema, J Wouter and Wilson, James F and Felix, Janine F and Divers, Jasmin and Lambert, Jean-Charles and Stafford, Jeanette M and Gaspoz, Jean-Michel and Smith, Jennifer A and Faul, Jessica D and Wang, Jie Jin and Ding, Jingzhong and Hirschhorn, Joel N and Attia, John and Whitfield, John B and Chalmers, John and Viikari, Jorma and Coresh, Josef and Denny, Joshua C and Karjalainen, Juha and Fernandes, Jyotika K and Endlich, Karlhans and Butterbach, Katja and Keene, Keith L and Lohman, Kurt and Portas, Laura and Launer, Lenore J and Lyytik{\"a}inen, Leo-Pekka and Yengo, Loic and Franke, Lude and Ferrucci, Luigi and Rose, Lynda M and Kedenko, Lyudmyla and Rao, Madhumathi and Struchalin, Maksim and Kleber, Marcus E and Cavalieri, Margherita and Haun, Margot and Cornelis, Marilyn C and Ciullo, Marina and Pirastu, Mario and de Andrade, Mariza and McEvoy, Mark A and Woodward, Mark and Adam, Martin and Cocca, Massimiliano and Nauck, Matthias and Imboden, Medea and Waldenberger, Melanie and Pruijm, Menno and Metzger, Marie and Stumvoll, Michael and Evans, Michele K and Sale, Michele M and K{\"a}h{\"o}nen, Mika and Boban, Mladen and Bochud, Murielle and Rheinberger, Myriam and Verweij, Niek and Bouatia-Naji, Nabila and Martin, Nicholas G and Hastie, Nick and Probst-Hensch, Nicole and Soranzo, Nicole and Devuyst, Olivier and Raitakari, Olli and Gottesman, Omri and Franco, Oscar H and Polasek, Ozren and Gasparini, Paolo and Munroe, Patricia B and Ridker, Paul M and Mitchell, Paul and Muntner, Paul and Meisinger, Christa and Smit, Johannes H and Kovacs, Peter and Wild, Philipp S and Froguel, Philippe and Rettig, Rainer and M{\"a}gi, Reedik and Biffar, Reiner and Schmidt, Reinhold and Middelberg, Rita P S and Carroll, Robert J and Penninx, Brenda W and Scott, Rodney J and Katz, Ronit and Sedaghat, Sanaz and Wild, Sarah H and Kardia, Sharon L R and Ulivi, Sheila and Hwang, Shih-Jen and Enroth, Stefan and Kloiber, Stefan and Trompet, Stella and Stengel, B{\'e}n{\'e}dicte and Hancock, Stephen J and Turner, Stephen T and Rosas, Sylvia E and Stracke, Sylvia and Harris, Tamara B and Zeller, Tanja and Zemunik, Tatijana and Lehtim{\"a}ki, Terho and Illig, Thomas and Aspelund, Thor and Nikopensius, Tiit and Esko, T{\~o}nu and Tanaka, Toshiko and Gyllensten, Ulf and V{\"o}lker, Uwe and Emilsson, Valur and Vitart, Veronique and Aalto, Ville and Gudnason, Vilmundur and Chouraki, Vincent and Chen, Wei-Min and Igl, Wilmar and M{\"a}rz, Winfried and Koenig, Wolfgang and Lieb, Wolfgang and Loos, Ruth J F and Liu, Yongmei and Snieder, Harold and Pramstaller, Peter P and Parsa, Afshin and O{\textquoteright}Connell, Jeffrey R and Susztak, Katalin and Hamet, Pavel and Tremblay, Johanne and de Boer, Ian H and B{\"o}ger, Carsten A and Goessling, Wolfram and Chasman, Daniel I and K{\"o}ttgen, Anna and Kao, W H Linda and Fox, Caroline S} } @article {7691, title = {Genetic studies of body mass index yield new insights for obesity biology.}, journal = {Nature}, volume = {518}, year = {2015}, month = {2015 Feb 12}, pages = {197-206}, abstract = {

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P~<~5~{\texttimes}~10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for \~{}2.7\% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20\% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

}, keywords = {Adipogenesis, Adiposity, Age Factors, Body Mass Index, Continental Population Groups, Energy Metabolism, Europe, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Glutamic Acid, Humans, Insulin, Male, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses}, issn = {1476-4687}, doi = {10.1038/nature14177}, author = {Locke, Adam E and Kahali, Bratati and Berndt, Sonja I and Justice, Anne E and Pers, Tune H and Day, Felix R and Powell, Corey and Vedantam, Sailaja and Buchkovich, Martin L and Yang, Jian and Croteau-Chonka, Damien C and Esko, T{\~o}nu and Fall, Tove and Ferreira, Teresa and Gustafsson, Stefan and Kutalik, Zolt{\'a}n and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Randall, Joshua C and Winkler, Thomas W and Wood, Andrew R and Workalemahu, Tsegaselassie and Faul, Jessica D and Smith, Jennifer A and Hua Zhao, Jing and Zhao, Wei and Chen, Jin and Fehrmann, Rudolf and Hedman, {\r A}sa K and Karjalainen, Juha and Schmidt, Ellen M and Absher, Devin and Amin, Najaf and Anderson, Denise and Beekman, Marian and Bolton, Jennifer L and Bragg-Gresham, Jennifer L and Buyske, Steven and Demirkan, Ayse and Deng, Guohong and Ehret, Georg B and Feenstra, Bjarke and Feitosa, Mary F and Fischer, Krista and Goel, Anuj and Gong, Jian and Jackson, Anne U and Kanoni, Stavroula and Kleber, Marcus E and Kristiansson, Kati and Lim, Unhee and Lotay, Vaneet and Mangino, Massimo and Mateo Leach, Irene and Medina-Gomez, Carolina and Medland, Sarah E and Nalls, Michael A and Palmer, Cameron D and Pasko, Dorota and Pechlivanis, Sonali and Peters, Marjolein J and Prokopenko, Inga and Shungin, Dmitry and Stan{\v c}{\'a}kov{\'a}, Alena and Strawbridge, Rona J and Ju Sung, Yun and Tanaka, Toshiko and Teumer, Alexander and Trompet, Stella and van der Laan, Sander W and van Setten, Jessica and Van Vliet-Ostaptchouk, Jana V and Wang, Zhaoming and Yengo, Loic and Zhang, Weihua and Isaacs, Aaron and Albrecht, Eva and Arnl{\"o}v, Johan and Arscott, Gillian M and Attwood, Antony P and Bandinelli, Stefania and Barrett, Amy and Bas, Isabelita N and Bellis, Claire and Bennett, Amanda J and Berne, Christian and Blagieva, Roza and Bl{\"u}her, Matthias and B{\"o}hringer, Stefan and Bonnycastle, Lori L and B{\"o}ttcher, Yvonne and Boyd, Heather A and Bruinenberg, Marcel and Caspersen, Ida H and Ida Chen, Yii-Der and Clarke, Robert and Daw, E Warwick and de Craen, Anton J M and Delgado, Graciela and Dimitriou, Maria and Doney, Alex S F and Eklund, Niina and Estrada, Karol and Eury, Elodie and Folkersen, Lasse and Fraser, Ross M and Garcia, Melissa E and Geller, Frank and Giedraitis, Vilmantas and Gigante, Bruna and Go, Alan S and Golay, Alain and Goodall, Alison H and Gordon, Scott D and Gorski, Mathias and Grabe, Hans-J{\"o}rgen and Grallert, Harald and Grammer, Tanja B and Gr{\"a}{\ss}ler, J{\"u}rgen and Gr{\"o}nberg, Henrik and Groves, Christopher J and Gusto, Ga{\"e}lle and Haessler, Jeffrey and Hall, Per and Haller, Toomas and Hallmans, Goran and Hartman, Catharina A and Hassinen, Maija and Hayward, Caroline and Heard-Costa, Nancy L and Helmer, Quinta and Hengstenberg, Christian and Holmen, Oddgeir and Hottenga, Jouke-Jan and James, Alan L and Jeff, Janina M and Johansson, {\r A}sa and Jolley, Jennifer and Juliusdottir, Thorhildur and Kinnunen, Leena and Koenig, Wolfgang and Koskenvuo, Markku and Kratzer, Wolfgang and Laitinen, Jaana and Lamina, Claudia and Leander, Karin and Lee, Nanette R and Lichtner, Peter and Lind, Lars and Lindstr{\"o}m, Jaana and Sin Lo, Ken and Lobbens, St{\'e}phane and Lorbeer, Roberto and Lu, Yingchang and Mach, Fran{\c c}ois and Magnusson, Patrik K E and Mahajan, Anubha and McArdle, Wendy L and McLachlan, Stela and Menni, Cristina and Merger, Sigrun and Mihailov, Evelin and Milani, Lili and Moayyeri, Alireza and Monda, Keri L and Morken, Mario A and Mulas, Antonella and M{\"u}ller, Gabriele and M{\"u}ller-Nurasyid, Martina and Musk, Arthur W and Nagaraja, Ramaiah and N{\"o}then, Markus M and Nolte, Ilja M and Pilz, Stefan and Rayner, Nigel W and Renstrom, Frida and Rettig, Rainer and Ried, Janina S and Ripke, Stephan and Robertson, Neil R and Rose, Lynda M and Sanna, Serena and Scharnagl, Hubert and Scholtens, Salome and Schumacher, Fredrick R and Scott, William R and Seufferlein, Thomas and Shi, Jianxin and Vernon Smith, Albert and Smolonska, Joanna and Stanton, Alice V and Steinthorsdottir, Valgerdur and Stirrups, Kathleen and Stringham, Heather M and Sundstr{\"o}m, Johan and Swertz, Morris A and Swift, Amy J and Syv{\"a}nen, Ann-Christine and Tan, Sian-Tsung and Tayo, Bamidele O and Thorand, Barbara and Thorleifsson, Gudmar and Tyrer, Jonathan P and Uh, Hae-Won and Vandenput, Liesbeth and Verhulst, Frank C and Vermeulen, Sita H and Verweij, Niek and Vonk, Judith M and Waite, Lindsay L and Warren, Helen R and Waterworth, Dawn and Weedon, Michael N and Wilkens, Lynne R and Willenborg, Christina and Wilsgaard, Tom and Wojczynski, Mary K and Wong, Andrew and Wright, Alan F and Zhang, Qunyuan and Brennan, Eoin P and Choi, Murim and Dastani, Zari and Drong, Alexander W and Eriksson, Per and Franco-Cereceda, Anders and G{\r a}din, Jesper R and Gharavi, Ali G and Goddard, Michael E and Handsaker, Robert E and Huang, Jinyan and Karpe, Fredrik and Kathiresan, Sekar and Keildson, Sarah and Kiryluk, Krzysztof and Kubo, Michiaki and Lee, Jong-Young and Liang, Liming and Lifton, Richard P and Ma, Baoshan and McCarroll, Steven A and McKnight, Amy J and Min, Josine L and Moffatt, Miriam F and Montgomery, Grant W and Murabito, Joanne M and Nicholson, George and Nyholt, Dale R and Okada, Yukinori and Perry, John R B and Dorajoo, Rajkumar and Reinmaa, Eva and Salem, Rany M and Sandholm, Niina and Scott, Robert A and Stolk, Lisette and Takahashi, Atsushi and Tanaka, Toshihiro and Van{\textquoteright}t Hooft, Ferdinand M and Vinkhuyzen, Anna A E and Westra, Harm-Jan and Zheng, Wei and Zondervan, Krina T and Heath, Andrew C and Arveiler, Dominique and Bakker, Stephan J L and Beilby, John and Bergman, Richard N and Blangero, John and Bovet, Pascal and Campbell, Harry and Caulfield, Mark J and Cesana, Giancarlo and Chakravarti, Aravinda and Chasman, Daniel I and Chines, Peter S and Collins, Francis S and Crawford, Dana C and Cupples, L Adrienne and Cusi, Daniele and Danesh, John and de Faire, Ulf and den Ruijter, Hester M and Dominiczak, Anna F and Erbel, Raimund and Erdmann, Jeanette and Eriksson, Johan G and Farrall, Martin and Felix, Stephan B and Ferrannini, Ele and Ferri{\`e}res, Jean and Ford, Ian and Forouhi, Nita G and Forrester, Terrence and Franco, Oscar H and Gansevoort, Ron T and Gejman, Pablo V and Gieger, Christian and Gottesman, Omri and Gudnason, Vilmundur and Gyllensten, Ulf and Hall, Alistair S and Harris, Tamara B and Hattersley, Andrew T and Hicks, Andrew A and Hindorff, Lucia A and Hingorani, Aroon D and Hofman, Albert and Homuth, Georg and Hovingh, G Kees and Humphries, Steve E and Hunt, Steven C and Hypp{\"o}nen, Elina and Illig, Thomas and Jacobs, Kevin B and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Johansen, Berit and Jousilahti, Pekka and Jukema, J Wouter and Jula, Antti M and Kaprio, Jaakko and Kastelein, John J P and Keinanen-Kiukaanniemi, Sirkka M and Kiemeney, Lambertus A and Knekt, Paul and Kooner, Jaspal S and Kooperberg, Charles and Kovacs, Peter and Kraja, Aldi T and Kumari, Meena and Kuusisto, Johanna and Lakka, Timo A and Langenberg, Claudia and Le Marchand, Loic and Lehtim{\"a}ki, Terho and Lyssenko, Valeriya and M{\"a}nnist{\"o}, Satu and Marette, Andr{\'e} and Matise, Tara C and McKenzie, Colin A and McKnight, Barbara and Moll, Frans L and Morris, Andrew D and Morris, Andrew P and Murray, Jeffrey C and Nelis, Mari and Ohlsson, Claes and Oldehinkel, Albertine J and Ong, Ken K and Madden, Pamela A F and Pasterkamp, Gerard and Peden, John F and Peters, Annette and Postma, Dirkje S and Pramstaller, Peter P and Price, Jackie F and Qi, Lu and Raitakari, Olli T and Rankinen, Tuomo and Rao, D C and Rice, Treva K and Ridker, Paul M and Rioux, John D and Ritchie, Marylyn D and Rudan, Igor and Salomaa, Veikko and Samani, Nilesh J and Saramies, Jouko and Sarzynski, Mark A and Schunkert, Heribert and Schwarz, Peter E H and Sever, Peter and Shuldiner, Alan R and Sinisalo, Juha and Stolk, Ronald P and Strauch, Konstantin and T{\"o}njes, Anke and Tr{\'e}gou{\"e}t, David-Alexandre and Tremblay, Angelo and Tremoli, Elena and Virtamo, Jarmo and Vohl, Marie-Claude and V{\"o}lker, Uwe and Waeber, Gerard and Willemsen, Gonneke and Witteman, Jacqueline C and Zillikens, M Carola and Adair, Linda S and Amouyel, Philippe and Asselbergs, Folkert W and Assimes, Themistocles L and Bochud, Murielle and Boehm, Bernhard O and Boerwinkle, Eric and Bornstein, Stefan R and Bottinger, Erwin P and Bouchard, Claude and Cauchi, St{\'e}phane and Chambers, John C and Chanock, Stephen J and Cooper, Richard S and de Bakker, Paul I W and Dedoussis, George and Ferrucci, Luigi and Franks, Paul W and Froguel, Philippe and Groop, Leif C and Haiman, Christopher A and Hamsten, Anders and Hui, Jennie and Hunter, David J and Hveem, Kristian and Kaplan, Robert C and Kivimaki, Mika and Kuh, Diana and Laakso, Markku and Liu, Yongmei and Martin, Nicholas G and M{\"a}rz, Winfried and Melbye, Mads and Metspalu, Andres and Moebus, Susanne and Munroe, Patricia B and Nj{\o}lstad, Inger and Oostra, Ben A and Palmer, Colin N A and Pedersen, Nancy L and Perola, Markus and P{\'e}russe, Louis and Peters, Ulrike and Power, Chris and Quertermous, Thomas and Rauramaa, Rainer and Rivadeneira, Fernando and Saaristo, Timo E and Saleheen, Danish and Sattar, Naveed and Schadt, Eric E and Schlessinger, David and Slagboom, P Eline and Snieder, Harold and Spector, Tim D and Thorsteinsdottir, Unnur and Stumvoll, Michael and Tuomilehto, Jaakko and Uitterlinden, Andr{\'e} G and Uusitupa, Matti and van der Harst, Pim and Walker, Mark and Wallaschofski, Henri and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wichmann, H-Erich and Wilson, James F and Zanen, Pieter and Borecki, Ingrid B and Deloukas, Panos and Fox, Caroline S and Heid, Iris M and O{\textquoteright}Connell, Jeffrey R and Strachan, David P and Stefansson, Kari and van Duijn, Cornelia M and Abecasis, Goncalo R and Franke, Lude and Frayling, Timothy M and McCarthy, Mark I and Visscher, Peter M and Scherag, Andr{\'e} and Willer, Cristen J and Boehnke, Michael and Mohlke, Karen L and Lindgren, Cecilia M and Beckmann, Jacques S and Barroso, In{\^e}s and North, Kari E and Ingelsson, Erik and Hirschhorn, Joel N and Loos, Ruth J F and Speliotes, Elizabeth K} } @article {7692, title = {New genetic loci link adipose and insulin biology to body fat distribution.}, journal = {Nature}, volume = {518}, year = {2015}, month = {2015 Feb 12}, pages = {187-96}, abstract = {

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P~<~5~{\texttimes}~10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

}, keywords = {Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Fat Distribution, Body Mass Index, Continental Population Groups, Epigenesis, Genetic, Europe, Female, Genome, Human, Genome-Wide Association Study, Humans, Insulin, Insulin Resistance, Male, Models, Biological, Neovascularization, Physiologic, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Characteristics, Transcription, Genetic, Waist-Hip Ratio}, issn = {1476-4687}, doi = {10.1038/nature14132}, author = {Shungin, Dmitry and Winkler, Thomas W and Croteau-Chonka, Damien C and Ferreira, Teresa and Locke, Adam E and M{\"a}gi, Reedik and Strawbridge, Rona J and Pers, Tune H and Fischer, Krista and Justice, Anne E and Workalemahu, Tsegaselassie and Wu, Joseph M W and Buchkovich, Martin L and Heard-Costa, Nancy L and Roman, Tamara S and Drong, Alexander W and Song, Ci and Gustafsson, Stefan and Day, Felix R and Esko, T{\~o}nu and Fall, Tove and Kutalik, Zolt{\'a}n and Luan, Jian{\textquoteright}an and Randall, Joshua C and Scherag, Andr{\'e} and Vedantam, Sailaja and Wood, Andrew R and Chen, Jin and Fehrmann, Rudolf and Karjalainen, Juha and Kahali, Bratati and Liu, Ching-Ti and Schmidt, Ellen M and Absher, Devin and Amin, Najaf and Anderson, Denise and Beekman, Marian and Bragg-Gresham, Jennifer L and Buyske, Steven and Demirkan, Ayse and Ehret, Georg B and Feitosa, Mary F and Goel, Anuj and Jackson, Anne U and Johnson, Toby and Kleber, Marcus E and Kristiansson, Kati and Mangino, Massimo and Mateo Leach, Irene and Medina-Gomez, Carolina and Palmer, Cameron D and Pasko, Dorota and Pechlivanis, Sonali and Peters, Marjolein J and Prokopenko, Inga and Stan{\v c}{\'a}kov{\'a}, Alena and Ju Sung, Yun and Tanaka, Toshiko and Teumer, Alexander and Van Vliet-Ostaptchouk, Jana V and Yengo, Loic and Zhang, Weihua and Albrecht, Eva and Arnl{\"o}v, Johan and Arscott, Gillian M and Bandinelli, Stefania and Barrett, Amy and Bellis, Claire and Bennett, Amanda J and Berne, Christian and Bl{\"u}her, Matthias and B{\"o}hringer, Stefan and Bonnet, Fabrice and B{\"o}ttcher, Yvonne and Bruinenberg, Marcel and Carba, Delia B and Caspersen, Ida H and Clarke, Robert and Daw, E Warwick and Deelen, Joris and Deelman, Ewa and Delgado, Graciela and Doney, Alex S F and Eklund, Niina and Erdos, Michael R and Estrada, Karol and Eury, Elodie and Friedrich, Nele and Garcia, Melissa E and Giedraitis, Vilmantas and Gigante, Bruna and Go, Alan S and Golay, Alain and Grallert, Harald and Grammer, Tanja B and Gr{\"a}{\ss}ler, J{\"u}rgen and Grewal, Jagvir and Groves, Christopher J and Haller, Toomas and Hallmans, Goran and Hartman, Catharina A and Hassinen, Maija and Hayward, Caroline and Heikkil{\"a}, Kauko and Herzig, Karl-Heinz and Helmer, Quinta and Hillege, Hans L and Holmen, Oddgeir and Hunt, Steven C and Isaacs, Aaron and Ittermann, Till and James, Alan L and Johansson, Ingegerd and Juliusdottir, Thorhildur and Kalafati, Ioanna-Panagiota and Kinnunen, Leena and Koenig, Wolfgang and Kooner, Ishminder K and Kratzer, Wolfgang and Lamina, Claudia and Leander, Karin and Lee, Nanette R and Lichtner, Peter and Lind, Lars and Lindstr{\"o}m, Jaana and Lobbens, St{\'e}phane and Lorentzon, Mattias and Mach, Fran{\c c}ois and Magnusson, Patrik K E and Mahajan, Anubha and McArdle, Wendy L and Menni, Cristina and Merger, Sigrun and Mihailov, Evelin and Milani, Lili and Mills, Rebecca and Moayyeri, Alireza and Monda, Keri L and Mooijaart, Simon P and M{\"u}hleisen, Thomas W and Mulas, Antonella and M{\"u}ller, Gabriele and M{\"u}ller-Nurasyid, Martina and Nagaraja, Ramaiah and Nalls, Michael A and Narisu, Narisu and Glorioso, Nicola and Nolte, Ilja M and Olden, Matthias and Rayner, Nigel W and Renstrom, Frida and Ried, Janina S and Robertson, Neil R and Rose, Lynda M and Sanna, Serena and Scharnagl, Hubert and Scholtens, Salome and Sennblad, Bengt and Seufferlein, Thomas and Sitlani, Colleen M and Vernon Smith, Albert and Stirrups, Kathleen and Stringham, Heather M and Sundstr{\"o}m, Johan and Swertz, Morris A and Swift, Amy J and Syv{\"a}nen, Ann-Christine and Tayo, Bamidele O and Thorand, Barbara and Thorleifsson, Gudmar and Tomaschitz, Andreas and Troffa, Chiara and van Oort, Floor V A and Verweij, Niek and Vonk, Judith M and Waite, Lindsay L and Wennauer, Roman and Wilsgaard, Tom and Wojczynski, Mary K and Wong, Andrew and Zhang, Qunyuan and Hua Zhao, Jing and Brennan, Eoin P and Choi, Murim and Eriksson, Per and Folkersen, Lasse and Franco-Cereceda, Anders and Gharavi, Ali G and Hedman, {\r A}sa K and Hivert, Marie-France and Huang, Jinyan and Kanoni, Stavroula and Karpe, Fredrik and Keildson, Sarah and Kiryluk, Krzysztof and Liang, Liming and Lifton, Richard P and Ma, Baoshan and McKnight, Amy J and McPherson, Ruth and Metspalu, Andres and Min, Josine L and Moffatt, Miriam F and Montgomery, Grant W and Murabito, Joanne M and Nicholson, George and Nyholt, Dale R and Olsson, Christian and Perry, John R B and Reinmaa, Eva and Salem, Rany M and Sandholm, Niina and Schadt, Eric E and Scott, Robert A and Stolk, Lisette and Vallejo, Edgar E and Westra, Harm-Jan and Zondervan, Krina T and Amouyel, Philippe and Arveiler, Dominique and Bakker, Stephan J L and Beilby, John and Bergman, Richard N and Blangero, John and Brown, Morris J and Burnier, Michel and Campbell, Harry and Chakravarti, Aravinda and Chines, Peter S and Claudi-Boehm, Simone and Collins, Francis S and Crawford, Dana C and Danesh, John and de Faire, Ulf and de Geus, Eco J C and D{\"o}rr, Marcus and Erbel, Raimund and Eriksson, Johan G and Farrall, Martin and Ferrannini, Ele and Ferri{\`e}res, Jean and Forouhi, Nita G and Forrester, Terrence and Franco, Oscar H and Gansevoort, Ron T and Gieger, Christian and Gudnason, Vilmundur and Haiman, Christopher A and Harris, Tamara B and Hattersley, Andrew T and Heli{\"o}vaara, Markku and Hicks, Andrew A and Hingorani, Aroon D and Hoffmann, Wolfgang and Hofman, Albert and Homuth, Georg and Humphries, Steve E and Hypp{\"o}nen, Elina and Illig, Thomas and J{\"a}rvelin, Marjo-Riitta and Johansen, Berit and Jousilahti, Pekka and Jula, Antti M and Kaprio, Jaakko and Kee, Frank and Keinanen-Kiukaanniemi, Sirkka M and Kooner, Jaspal S and Kooperberg, Charles and Kovacs, Peter and Kraja, Aldi T and Kumari, Meena and Kuulasmaa, Kari and Kuusisto, Johanna and Lakka, Timo A and Langenberg, Claudia and Le Marchand, Loic and Lehtim{\"a}ki, Terho and Lyssenko, Valeriya and M{\"a}nnist{\"o}, Satu and Marette, Andr{\'e} and Matise, Tara C and McKenzie, Colin A and McKnight, Barbara and Musk, Arthur W and M{\"o}hlenkamp, Stefan and Morris, Andrew D and Nelis, Mari and Ohlsson, Claes and Oldehinkel, Albertine J and Ong, Ken K and Palmer, Lyle J and Penninx, Brenda W and Peters, Annette and Pramstaller, Peter P and Raitakari, Olli T and Rankinen, Tuomo and Rao, D C and Rice, Treva K and Ridker, Paul M and Ritchie, Marylyn D and Rudan, Igor and Salomaa, Veikko and Samani, Nilesh J and Saramies, Jouko and Sarzynski, Mark A and Schwarz, Peter E H and Shuldiner, Alan R and Staessen, Jan A and Steinthorsdottir, Valgerdur and Stolk, Ronald P and Strauch, Konstantin and T{\"o}njes, Anke and Tremblay, Angelo and Tremoli, Elena and Vohl, Marie-Claude and V{\"o}lker, Uwe and Vollenweider, Peter and Wilson, James F and Witteman, Jacqueline C and Adair, Linda S and Bochud, Murielle and Boehm, Bernhard O and Bornstein, Stefan R and Bouchard, Claude and Cauchi, St{\'e}phane and Caulfield, Mark J and Chambers, John C and Chasman, Daniel I and Cooper, Richard S and Dedoussis, George and Ferrucci, Luigi and Froguel, Philippe and Grabe, Hans-J{\"o}rgen and Hamsten, Anders and Hui, Jennie and Hveem, Kristian and J{\"o}ckel, Karl-Heinz and Kivimaki, Mika and Kuh, Diana and Laakso, Markku and Liu, Yongmei and M{\"a}rz, Winfried and Munroe, Patricia B and Nj{\o}lstad, Inger and Oostra, Ben A and Palmer, Colin N A and Pedersen, Nancy L and Perola, Markus and P{\'e}russe, Louis and Peters, Ulrike and Power, Chris and Quertermous, Thomas and Rauramaa, Rainer and Rivadeneira, Fernando and Saaristo, Timo E and Saleheen, Danish and Sinisalo, Juha and Slagboom, P Eline and Snieder, Harold and Spector, Tim D and Thorsteinsdottir, Unnur and Stumvoll, Michael and Tuomilehto, Jaakko and Uitterlinden, Andr{\'e} G and Uusitupa, Matti and van der Harst, Pim and Veronesi, Giovanni and Walker, Mark and Wareham, Nicholas J and Watkins, Hugh and Wichmann, H-Erich and Abecasis, Goncalo R and Assimes, Themistocles L and Berndt, Sonja I and Boehnke, Michael and Borecki, Ingrid B and Deloukas, Panos and Franke, Lude and Frayling, Timothy M and Groop, Leif C and Hunter, David J and Kaplan, Robert C and O{\textquoteright}Connell, Jeffrey R and Qi, Lu and Schlessinger, David and Strachan, David P and Stefansson, Kari and van Duijn, Cornelia M and Willer, Cristen J and Visscher, Peter M and Yang, Jian and Hirschhorn, Joel N and Zillikens, M Carola and McCarthy, Mark I and Speliotes, Elizabeth K and North, Kari E and Fox, Caroline S and Barroso, In{\^e}s and Franks, Paul W and Ingelsson, Erik and Heid, Iris M and Loos, Ruth J F and Cupples, L Adrienne and Morris, Andrew P and Lindgren, Cecilia M and Mohlke, Karen L} } @article {1907, title = {Genome-wide association and functional follow-up reveals new loci for kidney function.}, journal = {PLoS Genet}, volume = {8}, year = {2012}, month = {2012}, pages = {e1002584}, abstract = {

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

}, keywords = {African Americans, Aged, Animals, Caspase 9, Cyclin-Dependent Kinases, DEAD-box RNA Helicases, DNA Helicases, European Continental Ancestry Group, Female, Follow-Up Studies, Gene Knockdown Techniques, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Kidney Failure, Chronic, Male, Middle Aged, Phosphoric Diester Hydrolases, Zebrafish}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002584}, author = {Pattaro, Cristian and K{\"o}ttgen, Anna and Teumer, Alexander and Garnaas, Maija and B{\"o}ger, Carsten A and Fuchsberger, Christian and Olden, Matthias and Chen, Ming-Huei and Tin, Adrienne and Taliun, Daniel and Li, Man and Gao, Xiaoyi and Gorski, Mathias and Yang, Qiong and Hundertmark, Claudia and Foster, Meredith C and O{\textquoteright}Seaghdha, Conall M and Glazer, Nicole and Isaacs, Aaron and Liu, Ching-Ti and Smith, Albert V and O{\textquoteright}Connell, Jeffrey R and Struchalin, Maksim and Tanaka, Toshiko and Li, Guo and Johnson, Andrew D and Gierman, Hinco J and Feitosa, Mary and Hwang, Shih-Jen and Atkinson, Elizabeth J and Lohman, Kurt and Cornelis, Marilyn C and Johansson, {\r A}sa and T{\"o}njes, Anke and Dehghan, Abbas and Chouraki, Vincent and Holliday, Elizabeth G and Sorice, Rossella and Kutalik, Zolt{\'a}n and Lehtim{\"a}ki, Terho and Esko, T{\~o}nu and Deshmukh, Harshal and Ulivi, Sheila and Chu, Audrey Y and Murgia, Federico and Trompet, Stella and Imboden, Medea and Kollerits, Barbara and Pistis, Giorgio and Harris, Tamara B and Launer, Lenore J and Aspelund, Thor and Eiriksdottir, Gudny and Mitchell, Braxton D and Boerwinkle, Eric and Schmidt, Helena and Cavalieri, Margherita and Rao, Madhumathi and Hu, Frank B and Demirkan, Ayse and Oostra, Ben A and de Andrade, Mariza and Turner, Stephen T and Ding, Jingzhong and Andrews, Jeanette S and Freedman, Barry I and Koenig, Wolfgang and Illig, Thomas and D{\"o}ring, Angela and Wichmann, H-Erich and Kolcic, Ivana and Zemunik, Tatijana and Boban, Mladen and Minelli, Cosetta and Wheeler, Heather E and Igl, Wilmar and Zaboli, Ghazal and Wild, Sarah H and Wright, Alan F and Campbell, Harry and Ellinghaus, David and N{\"o}thlings, Ute and Jacobs, Gunnar and Biffar, Reiner and Endlich, Karlhans and Ernst, Florian and Homuth, Georg and Kroemer, Heyo K and Nauck, Matthias and Stracke, Sylvia and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Kovacs, Peter and Stumvoll, Michael and M{\"a}gi, Reedik and Hofman, Albert and Uitterlinden, Andr{\'e} G and Rivadeneira, Fernando and Aulchenko, Yurii S and Polasek, Ozren and Hastie, Nick and Vitart, Veronique and Helmer, Catherine and Wang, Jie Jin and Ruggiero, Daniela and Bergmann, Sven and K{\"a}h{\"o}nen, Mika and Viikari, Jorma and Nikopensius, Tiit and Province, Michael and Ketkar, Shamika and Colhoun, Helen and Doney, Alex and Robino, Antonietta and Giulianini, Franco and Kr{\"a}mer, Bernhard K and Portas, Laura and Ford, Ian and Buckley, Brendan M and Adam, Martin and Thun, Gian-Andri and Paulweber, Bernhard and Haun, Margot and Sala, Cinzia and Metzger, Marie and Mitchell, Paul and Ciullo, Marina and Kim, Stuart K and Vollenweider, Peter and Raitakari, Olli and Metspalu, Andres and Palmer, Colin and Gasparini, Paolo and Pirastu, Mario and Jukema, J Wouter and Probst-Hensch, Nicole M and Kronenberg, Florian and Toniolo, Daniela and Gudnason, Vilmundur and Shuldiner, Alan R and Coresh, Josef and Schmidt, Reinhold and Ferrucci, Luigi and Siscovick, David S and van Duijn, Cornelia M and Borecki, Ingrid and Kardia, Sharon L R and Liu, Yongmei and Curhan, Gary C and Rudan, Igor and Gyllensten, Ulf and Wilson, James F and Franke, Andre and Pramstaller, Peter P and Rettig, Rainer and Prokopenko, Inga and Witteman, Jacqueline C M and Hayward, Caroline and Ridker, Paul and Parsa, Afshin and Bochud, Murielle and Heid, Iris M and Goessling, Wolfram and Chasman, Daniel I and Kao, W H Linda and Fox, Caroline S} } @article {1980, title = {Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.}, journal = {Hum Mol Genet}, volume = {21}, year = {2012}, month = {2012 Dec 15}, pages = {5329-43}, abstract = {

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 {\texttimes} 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 {\texttimes} 10(-4)-2.2 {\texttimes} 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

}, keywords = {Amino Acid Transport Systems, Basic, Antigens, CD98 Heavy Chain, Genetic Predisposition to Disease, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Inhibin-beta Subunits, Intracellular Signaling Peptides and Proteins, Low Density Lipoprotein Receptor-Related Protein-2, Membrane Proteins, Polymorphism, Single Nucleotide}, issn = {1460-2083}, doi = {10.1093/hmg/dds369}, author = {Chasman, Daniel I and Fuchsberger, Christian and Pattaro, Cristian and Teumer, Alexander and B{\"o}ger, Carsten A and Endlich, Karlhans and Olden, Matthias and Chen, Ming-Huei and Tin, Adrienne and Taliun, Daniel and Li, Man and Gao, Xiaoyi and Gorski, Mathias and Yang, Qiong and Hundertmark, Claudia and Foster, Meredith C and O{\textquoteright}Seaghdha, Conall M and Glazer, Nicole and Isaacs, Aaron and Liu, Ching-Ti and Smith, Albert V and O{\textquoteright}Connell, Jeffrey R and Struchalin, Maksim and Tanaka, Toshiko and Li, Guo and Johnson, Andrew D and Gierman, Hinco J and Feitosa, Mary F and Hwang, Shih-Jen and Atkinson, Elizabeth J and Lohman, Kurt and Cornelis, Marilyn C and Johansson, {\r A}sa and T{\"o}njes, Anke and Dehghan, Abbas and Lambert, Jean-Charles and Holliday, Elizabeth G and Sorice, Rossella and Kutalik, Zolt{\'a}n and Lehtim{\"a}ki, Terho and Esko, T{\~o}nu and Deshmukh, Harshal and Ulivi, Sheila and Chu, Audrey Y and Murgia, Federico and Trompet, Stella and Imboden, Medea and Coassin, Stefan and Pistis, Giorgio and Harris, Tamara B and Launer, Lenore J and Aspelund, Thor and Eiriksdottir, Gudny and Mitchell, Braxton D and Boerwinkle, Eric and Schmidt, Helena and Cavalieri, Margherita and Rao, Madhumathi and Hu, Frank and Demirkan, Ayse and Oostra, Ben A and de Andrade, Mariza and Turner, Stephen T and Ding, Jingzhong and Andrews, Jeanette S and Freedman, Barry I and Giulianini, Franco and Koenig, Wolfgang and Illig, Thomas and Meisinger, Christa and Gieger, Christian and Zgaga, Lina and Zemunik, Tatijana and Boban, Mladen and Minelli, Cosetta and Wheeler, Heather E and Igl, Wilmar and Zaboli, Ghazal and Wild, Sarah H and Wright, Alan F and Campbell, Harry and Ellinghaus, David and N{\"o}thlings, Ute and Jacobs, Gunnar and Biffar, Reiner and Ernst, Florian and Homuth, Georg and Kroemer, Heyo K and Nauck, Matthias and Stracke, Sylvia and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Kovacs, Peter and Stumvoll, Michael and M{\"a}gi, Reedik and Hofman, Albert and Uitterlinden, Andr{\'e} G and Rivadeneira, Fernando and Aulchenko, Yurii S and Polasek, Ozren and Hastie, Nick and Vitart, Veronique and Helmer, Catherine and Wang, Jie Jin and Stengel, B{\'e}n{\'e}dicte and Ruggiero, Daniela and Bergmann, Sven and K{\"a}h{\"o}nen, Mika and Viikari, Jorma and Nikopensius, Tiit and Province, Michael and Ketkar, Shamika and Colhoun, Helen and Doney, Alex and Robino, Antonietta and Kr{\"a}mer, Bernhard K and Portas, Laura and Ford, Ian and Buckley, Brendan M and Adam, Martin and Thun, Gian-Andri and Paulweber, Bernhard and Haun, Margot and Sala, Cinzia and Mitchell, Paul and Ciullo, Marina and Kim, Stuart K and Vollenweider, Peter and Raitakari, Olli and Metspalu, Andres and Palmer, Colin and Gasparini, Paolo and Pirastu, Mario and Jukema, J Wouter and Probst-Hensch, Nicole M and Kronenberg, Florian and Toniolo, Daniela and Gudnason, Vilmundur and Shuldiner, Alan R and Coresh, Josef and Schmidt, Reinhold and Ferrucci, Luigi and Siscovick, David S and van Duijn, Cornelia M and Borecki, Ingrid B and Kardia, Sharon L R and Liu, Yongmei and Curhan, Gary C and Rudan, Igor and Gyllensten, Ulf and Wilson, James F and Franke, Andre and Pramstaller, Peter P and Rettig, Rainer and Prokopenko, Inga and Witteman, Jacqueline and Hayward, Caroline and Ridker, Paul M and Parsa, Afshin and Bochud, Murielle and Heid, Iris M and Kao, W H Linda and Fox, Caroline S and K{\"o}ttgen, Anna} } @article {1790, title = {Multiple loci are associated with white blood cell phenotypes.}, journal = {PLoS Genet}, volume = {7}, year = {2011}, month = {2011 Jun}, pages = {e1002113}, abstract = {

White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds.

}, keywords = {Genetic Loci, Genome-Wide Association Study, Humans, Leukocyte Count, Leukocytes, Molecular Epidemiology, Multigene Family, Phenotype, Polymorphism, Single Nucleotide, Ubiquitin-Protein Ligases}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002113}, author = {Nalls, Michael A and Couper, David J and Tanaka, Toshiko and van Rooij, Frank J A and Chen, Ming-Huei and Smith, Albert V and Toniolo, Daniela and Zakai, Neil A and Yang, Qiong and Greinacher, Andreas and Wood, Andrew R and Garcia, Melissa and Gasparini, Paolo and Liu, Yongmei and Lumley, Thomas and Folsom, Aaron R and Reiner, Alex P and Gieger, Christian and Lagou, Vasiliki and Felix, Janine F and V{\"o}lzke, Henry and Gouskova, Natalia A and Biffi, Alessandro and D{\"o}ring, Angela and V{\"o}lker, Uwe and Chong, Sean and Wiggins, Kerri L and Rendon, Augusto and Dehghan, Abbas and Moore, Matt and Taylor, Kent and Wilson, James G and Lettre, Guillaume and Hofman, Albert and Bis, Joshua C and Pirastu, Nicola and Fox, Caroline S and Meisinger, Christa and Sambrook, Jennifer and Arepalli, Sampath and Nauck, Matthias and Prokisch, Holger and Stephens, Jonathan and Glazer, Nicole L and Cupples, L Adrienne and Okada, Yukinori and Takahashi, Atsushi and Kamatani, Yoichiro and Matsuda, Koichi and Tsunoda, Tatsuhiko and Tanaka, Toshihiro and Kubo, Michiaki and Nakamura, Yusuke and Yamamoto, Kazuhiko and Kamatani, Naoyuki and Stumvoll, Michael and T{\"o}njes, Anke and Prokopenko, Inga and Illig, Thomas and Patel, Kushang V and Garner, Stephen F and Kuhnel, Brigitte and Mangino, Massimo and Oostra, Ben A and Thein, Swee Lay and Coresh, Josef and Wichmann, H-Erich and Menzel, Stephan and Lin, JingPing and Pistis, Giorgio and Uitterlinden, Andr{\'e} G and Spector, Tim D and Teumer, Alexander and Eiriksdottir, Gudny and Gudnason, Vilmundur and Bandinelli, Stefania and Frayling, Timothy M and Chakravarti, Aravinda and van Duijn, Cornelia M and Melzer, David and Ouwehand, Willem H and Levy, Daniel and Boerwinkle, Eric and Singleton, Andrew B and Hernandez, Dena G and Longo, Dan L and Soranzo, Nicole and Witteman, Jacqueline C M and Psaty, Bruce M and Ferrucci, Luigi and Harris, Tamara B and O{\textquoteright}Donnell, Christopher J and Ganesh, Santhi K} } @article {1734, title = {Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.}, journal = {Nat Genet}, volume = {42}, year = {2010}, month = {2010 Dec}, pages = {1077-85}, abstract = {

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 {\texttimes} 10$^{-}$$^{6}$$^{0}$) and 9q31.2 (P = 2.2 {\texttimes} 10$^{-}${\textthreesuperior}{\textthreesuperior}), we identified 30 new menarche loci (all P < 5 {\texttimes} 10$^{-}$$^{8}$) and found suggestive evidence for a further 10 loci (P < 1.9 {\texttimes} 10$^{-}$$^{6}$). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

}, keywords = {Adolescent, Aging, Body Height, Body Size, Child, DNA Copy Number Variations, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Inheritance Patterns, Menarche, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, Time Factors}, issn = {1546-1718}, doi = {10.1038/ng.714}, author = {Elks, Cathy E and Perry, John R B and Sulem, Patrick and Chasman, Daniel I and Franceschini, Nora and He, Chunyan and Lunetta, Kathryn L and Visser, Jenny A and Byrne, Enda M and Cousminer, Diana L and Gudbjartsson, Daniel F and Esko, T{\~o}nu and Feenstra, Bjarke and Hottenga, Jouke-Jan and Koller, Daniel L and Kutalik, Zolt{\'a}n and Lin, Peng and Mangino, Massimo and Marongiu, Mara and McArdle, Patrick F and Smith, Albert V and Stolk, Lisette and van Wingerden, Sophie H and Zhao, Jing Hua and Albrecht, Eva and Corre, Tanguy and Ingelsson, Erik and Hayward, Caroline and Magnusson, Patrik K E and Smith, Erin N and Ulivi, Shelia and Warrington, Nicole M and Zgaga, Lina and Alavere, Helen and Amin, Najaf and Aspelund, Thor and Bandinelli, Stefania and Barroso, In{\^e}s and Berenson, Gerald S and Bergmann, Sven and Blackburn, Hannah and Boerwinkle, Eric and Buring, Julie E and Busonero, Fabio and Campbell, Harry and Chanock, Stephen J and Chen, Wei and Cornelis, Marilyn C and Couper, David and Coviello, Andrea D and d{\textquoteright}Adamo, Pio and de Faire, Ulf and de Geus, Eco J C and Deloukas, Panos and D{\"o}ring, Angela and Smith, George Davey and Easton, Douglas F and Eiriksdottir, Gudny and Emilsson, Valur and Eriksson, Johan and Ferrucci, Luigi and Folsom, Aaron R and Foroud, Tatiana and Garcia, Melissa and Gasparini, Paolo and Geller, Frank and Gieger, Christian and Gudnason, Vilmundur and Hall, Per and Hankinson, Susan E and Ferreli, Liana and Heath, Andrew C and Hernandez, Dena G and Hofman, Albert and Hu, Frank B and Illig, Thomas and J{\"a}rvelin, Marjo-Riitta and Johnson, Andrew D and Karasik, David and Khaw, Kay-Tee and Kiel, Douglas P and Kilpel{\"a}inen, Tuomas O and Kolcic, Ivana and Kraft, Peter and Launer, Lenore J and Laven, Joop S E and Li, Shengxu and Liu, Jianjun and Levy, Daniel and Martin, Nicholas G and McArdle, Wendy L and Melbye, Mads and Mooser, Vincent and Murray, Jeffrey C and Murray, Sarah S and Nalls, Michael A and Navarro, Pau and Nelis, Mari and Ness, Andrew R and Northstone, Kate and Oostra, Ben A and Peacock, Munro and Palmer, Lyle J and Palotie, Aarno and Par{\'e}, Guillaume and Parker, Alex N and Pedersen, Nancy L and Peltonen, Leena and Pennell, Craig E and Pharoah, Paul and Polasek, Ozren and Plump, Andrew S and Pouta, Anneli and Porcu, Eleonora and Rafnar, Thorunn and Rice, John P and Ring, Susan M and Rivadeneira, Fernando and Rudan, Igor and Sala, Cinzia and Salomaa, Veikko and Sanna, Serena and Schlessinger, David and Schork, Nicholas J and Scuteri, Angelo and Segr{\`e}, Ayellet V and Shuldiner, Alan R and Soranzo, Nicole and Sovio, Ulla and Srinivasan, Sathanur R and Strachan, David P and Tammesoo, Mar-Liis and Tikkanen, Emmi and Toniolo, Daniela and Tsui, Kim and Tryggvadottir, Laufey and Tyrer, Jonathon and Uda, Manuela and van Dam, Rob M and van Meurs, Joyce B J and Vollenweider, Peter and Waeber, Gerard and Wareham, Nicholas J and Waterworth, Dawn M and Weedon, Michael N and Wichmann, H Erich and Willemsen, Gonneke and Wilson, James F and Wright, Alan F and Young, Lauren and Zhai, Guangju and Zhuang, Wei Vivian and Bierut, Laura J and Boomsma, Dorret I and Boyd, Heather A and Crisponi, Laura and Demerath, Ellen W and van Duijn, Cornelia M and Econs, Michael J and Harris, Tamara B and Hunter, David J and Loos, Ruth J F and Metspalu, Andres and Montgomery, Grant W and Ridker, Paul M and Spector, Tim D and Streeten, Elizabeth A and Stefansson, Kari and Thorsteinsdottir, Unnur and Uitterlinden, Andr{\'e} G and Widen, Elisabeth and Murabito, Joanne M and Ong, Ken K and Murray, Anna} }