@article {10481, title = {1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.}, journal = {Sci Rep}, volume = {7}, year = {2017}, month = {2017 04 28}, pages = {45040}, abstract = {

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5\% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 {\texttimes} 10 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.

}, keywords = {Computational Biology, Gene Frequency, Genetic Loci, Genome, Human, Genome-Wide Association Study, Genotyping Techniques, Humans, Kidney, Polymorphism, Single Nucleotide}, issn = {2045-2322}, doi = {10.1038/srep45040}, author = {Gorski, Mathias and van der Most, Peter J and Teumer, Alexander and Chu, Audrey Y and Li, Man and Mijatovic, Vladan and Nolte, Ilja M and Cocca, Massimiliano and Taliun, Daniel and Gomez, Felicia and Li, Yong and Tayo, Bamidele and Tin, Adrienne and Feitosa, Mary F and Aspelund, Thor and Attia, John and Biffar, Reiner and Bochud, Murielle and Boerwinkle, Eric and Borecki, Ingrid and Bottinger, Erwin P and Chen, Ming-Huei and Chouraki, Vincent and Ciullo, Marina and Coresh, Josef and Cornelis, Marilyn C and Curhan, Gary C and d{\textquoteright}Adamo, Adamo Pio and Dehghan, Abbas and Dengler, Laura and Ding, Jingzhong and Eiriksdottir, Gudny and Endlich, Karlhans and Enroth, Stefan and Esko, T{\~o}nu and Franco, Oscar H and Gasparini, Paolo and Gieger, Christian and Girotto, Giorgia and Gottesman, Omri and Gudnason, Vilmundur and Gyllensten, Ulf and Hancock, Stephen J and Harris, Tamara B and Helmer, Catherine and H{\"o}llerer, Simon and Hofer, Edith and Hofman, Albert and Holliday, Elizabeth G and Homuth, Georg and Hu, Frank B and Huth, Cornelia and Hutri-K{\"a}h{\"o}nen, Nina and Hwang, Shih-Jen and Imboden, Medea and Johansson, {\r A}sa and K{\"a}h{\"o}nen, Mika and K{\"o}nig, Wolfgang and Kramer, Holly and Kr{\"a}mer, Bernhard K and Kumar, Ashish and Kutalik, Zolt{\'a}n and Lambert, Jean-Charles and Launer, Lenore J and Lehtim{\"a}ki, Terho and de Borst, Martin and Navis, Gerjan and Swertz, Morris and Liu, Yongmei and Lohman, Kurt and Loos, Ruth J F and Lu, Yingchang and Lyytik{\"a}inen, Leo-Pekka and McEvoy, Mark A and Meisinger, Christa and Meitinger, Thomas and Metspalu, Andres and Metzger, Marie and Mihailov, Evelin and Mitchell, Paul and Nauck, Matthias and Oldehinkel, Albertine J and Olden, Matthias and Wjh Penninx, Brenda and Pistis, Giorgio and Pramstaller, Peter P and Probst-Hensch, Nicole and Raitakari, Olli T and Rettig, Rainer and Ridker, Paul M and Rivadeneira, Fernando and Robino, Antonietta and Rosas, Sylvia E and Ruderfer, Douglas and Ruggiero, Daniela and Saba, Yasaman and Sala, Cinzia and Schmidt, Helena and Schmidt, Reinhold and Scott, Rodney J and Sedaghat, Sanaz and Smith, Albert V and Sorice, Rossella and Stengel, B{\'e}n{\'e}dicte and Stracke, Sylvia and Strauch, Konstantin and Toniolo, Daniela and Uitterlinden, Andr{\'e} G and Ulivi, Sheila and Viikari, Jorma S and V{\"o}lker, Uwe and Vollenweider, Peter and V{\"o}lzke, Henry and Vuckovic, Dragana and Waldenberger, Melanie and Jin Wang, Jie and Yang, Qiong and Chasman, Daniel I and Tromp, Gerard and Snieder, Harold and Heid, Iris M and Fox, Caroline S and K{\"o}ttgen, Anna and Pattaro, Cristian and B{\"o}ger, Carsten A and Fuchsberger, Christian} } @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 {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 {1906, title = {Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.}, journal = {Nat Genet}, volume = {44}, year = {2012}, month = {2012 Mar}, pages = {260-8}, abstract = {

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 {\texttimes} 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

}, keywords = {Age Factors, DNA Helicases, DNA Primase, DNA Repair, DNA Repair Enzymes, DNA-Directed DNA Polymerase, European Continental Ancestry Group, Exodeoxyribonucleases, Female, Genetic Loci, Genome-Wide Association Study, Humans, Immunity, Menopause, Polymorphism, Single Nucleotide, Proteins}, issn = {1546-1718}, doi = {10.1038/ng.1051}, author = {Stolk, Lisette and Perry, John R B and Chasman, Daniel I and He, Chunyan and Mangino, Massimo and Sulem, Patrick and Barbalic, Maja and Broer, Linda and Byrne, Enda M and Ernst, Florian and Esko, T{\~o}nu and Franceschini, Nora and Gudbjartsson, Daniel F and Hottenga, Jouke-Jan and Kraft, Peter and McArdle, Patrick F and Porcu, Eleonora and Shin, So-Youn and Smith, Albert V and van Wingerden, Sophie and Zhai, Guangju and Zhuang, Wei V and Albrecht, Eva and Alizadeh, Behrooz Z and Aspelund, Thor and Bandinelli, Stefania and Lauc, Lovorka Barac and Beckmann, Jacques S and Boban, Mladen and Boerwinkle, Eric and Broekmans, Frank J and Burri, Andrea and Campbell, Harry and Chanock, Stephen J and Chen, Constance and Cornelis, Marilyn C and Corre, Tanguy and Coviello, Andrea D and d{\textquoteright}Adamo, Pio and Davies, Gail and de Faire, Ulf and de Geus, Eco J C and Deary, Ian J and Dedoussis, George V Z and Deloukas, Panagiotis and Ebrahim, Shah and Eiriksdottir, Gudny and Emilsson, Valur and Eriksson, Johan G and Fauser, Bart C J M and Ferreli, Liana and Ferrucci, Luigi and Fischer, Krista and Folsom, Aaron R and Garcia, Melissa E and Gasparini, Paolo and Gieger, Christian and Glazer, Nicole and Grobbee, Diederick E and Hall, Per and Haller, Toomas and Hankinson, Susan E and Hass, Merli and Hayward, Caroline and Heath, Andrew C and Hofman, Albert and Ingelsson, Erik and Janssens, A Cecile J W and Johnson, Andrew D and Karasik, David and Kardia, Sharon L R and Keyzer, Jules and Kiel, Douglas P and Kolcic, Ivana and Kutalik, Zolt{\'a}n and Lahti, Jari and Lai, Sandra and Laisk, Triin and Laven, Joop S E and Lawlor, Debbie A and Liu, Jianjun and Lopez, Lorna M and Louwers, Yvonne V and Magnusson, Patrik K E and Marongiu, Mara and Martin, Nicholas G and Klaric, Irena Martinovic and Masciullo, Corrado and McKnight, Barbara and Medland, Sarah E and Melzer, David and Mooser, Vincent and Navarro, Pau and Newman, Anne B and Nyholt, Dale R and Onland-Moret, N Charlotte and Palotie, Aarno and Par{\'e}, Guillaume and Parker, Alex N and Pedersen, Nancy L and Peeters, Petra H M and Pistis, Giorgio and Plump, Andrew S and Polasek, Ozren and Pop, Victor J M and Psaty, Bruce M and R{\"a}ikk{\"o}nen, Katri and Rehnberg, Emil and Rotter, Jerome I and Rudan, Igor and Sala, Cinzia and Salumets, Andres and Scuteri, Angelo and Singleton, Andrew and Smith, Jennifer A and Snieder, Harold and Soranzo, Nicole and Stacey, Simon N and Starr, John M and Stathopoulou, Maria G and Stirrups, Kathleen and Stolk, Ronald P and Styrkarsdottir, Unnur and Sun, Yan V and Tenesa, Albert and Thorand, Barbara and Toniolo, Daniela and Tryggvadottir, Laufey and Tsui, Kim and Ulivi, Sheila and van Dam, Rob M and van der Schouw, Yvonne T and van Gils, Carla H and van Nierop, Peter and Vink, Jacqueline M and Visscher, Peter M and Voorhuis, Marlies and Waeber, Gerard and Wallaschofski, Henri and Wichmann, H Erich and Widen, Elisabeth and Wijnands-van Gent, Colette J M and Willemsen, Gonneke and Wilson, James F and Wolffenbuttel, Bruce H R and Wright, Alan F and Yerges-Armstrong, Laura M and Zemunik, Tatijana and Zgaga, Lina and Zillikens, M Carola and Zygmunt, Marek and Arnold, Alice M and Boomsma, Dorret I and Buring, Julie E and Crisponi, Laura and Demerath, Ellen W and Gudnason, Vilmundur and Harris, Tamara B and Hu, Frank B and Hunter, David J and Launer, Lenore J and Metspalu, Andres and Montgomery, Grant W and Oostra, Ben A and Ridker, Paul M and Sanna, Serena and Schlessinger, David and Spector, Tim D and Stefansson, Kari and Streeten, Elizabeth A and Thorsteinsdottir, Unnur and Uda, Manuela and Uitterlinden, Andr{\'e} G and van Duijn, Cornelia M and V{\"o}lzke, Henry and Murray, Anna and Murabito, Joanne M and Visser, Jenny A and Lunetta, Kathryn L} } @article {1840, title = {Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.}, journal = {Nat Genet}, volume = {43}, year = {2011}, month = {2011 Oct}, pages = {1005-11}, abstract = {

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 {\texttimes} 10(-8) to P = 2.3 {\texttimes} 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

}, keywords = {Arteries, Blood Pressure, Case-Control Studies, Follow-Up Studies, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Linkage Disequilibrium, Polymorphism, Single Nucleotide}, issn = {1546-1718}, doi = {10.1038/ng.922}, author = {Wain, Louise V and Verwoert, Germaine C and O{\textquoteright}Reilly, Paul F and Shi, Gang and Johnson, Toby and Johnson, Andrew D and Bochud, Murielle and Rice, Kenneth M and Henneman, Peter and Smith, Albert V and Ehret, Georg B and Amin, Najaf and Larson, Martin G and Mooser, Vincent and Hadley, David and D{\"o}rr, Marcus and Bis, Joshua C and Aspelund, Thor and Esko, T{\~o}nu and Janssens, A Cecile J W and Zhao, Jing Hua and Heath, Simon and Laan, Maris and Fu, Jingyuan and Pistis, Giorgio and Luan, Jian{\textquoteright}an and Arora, Pankaj and Lucas, Gavin and Pirastu, Nicola and Pichler, Irene and Jackson, Anne U and Webster, Rebecca J and Zhang, Feng and Peden, John F and Schmidt, Helena and Tanaka, Toshiko and Campbell, Harry and Igl, Wilmar and Milaneschi, Yuri and Hottenga, Jouke-Jan and Vitart, Veronique and Chasman, Daniel I and Trompet, Stella and Bragg-Gresham, Jennifer L and Alizadeh, Behrooz Z and Chambers, John C and Guo, Xiuqing and Lehtim{\"a}ki, Terho and Kuhnel, Brigitte and Lopez, Lorna M and Polasek, Ozren and Boban, Mladen and Nelson, Christopher P and Morrison, Alanna C and Pihur, Vasyl and Ganesh, Santhi K and Hofman, Albert and Kundu, Suman and Mattace-Raso, Francesco U S and Rivadeneira, Fernando and Sijbrands, Eric J G and Uitterlinden, Andr{\'e} G and Hwang, Shih-Jen and Vasan, Ramachandran S and Wang, Thomas J and Bergmann, Sven and Vollenweider, Peter and Waeber, Gerard and Laitinen, Jaana and Pouta, Anneli and Zitting, Paavo and McArdle, Wendy L and Kroemer, Heyo K and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Glazer, Nicole L and Taylor, Kent D and Harris, Tamara B and Alavere, Helene and Haller, Toomas and Keis, Aime and Tammesoo, Mari-Liis and Aulchenko, Yurii and Barroso, In{\^e}s and Khaw, Kay-Tee and Galan, Pilar and Hercberg, Serge and Lathrop, Mark and Eyheramendy, Susana and Org, Elin and S{\~o}ber, Siim and Lu, Xiaowen and Nolte, Ilja M and Penninx, Brenda W and Corre, Tanguy and Masciullo, Corrado and Sala, Cinzia and Groop, Leif and Voight, Benjamin F and Melander, Olle and O{\textquoteright}Donnell, Christopher J and Salomaa, Veikko and d{\textquoteright}Adamo, Adamo Pio and Fabretto, Antonella and Faletra, Flavio and Ulivi, Sheila and Del Greco, Fabiola M and Facheris, Maurizio and Collins, Francis S and Bergman, Richard N and Beilby, John P and Hung, Joseph and Musk, A William and Mangino, Massimo and Shin, So-Youn and Soranzo, Nicole and Watkins, Hugh and Goel, Anuj and Hamsten, Anders and Gider, Pierre and Loitfelder, Marisa and Zeginigg, Marion and Hernandez, Dena and Najjar, Samer S and Navarro, Pau and Wild, Sarah H and Corsi, Anna Maria and Singleton, Andrew and de Geus, Eco J C and Willemsen, Gonneke and Parker, Alex N and Rose, Lynda M and Buckley, Brendan and Stott, David and Orru, Marco and Uda, Manuela and van der Klauw, Melanie M and Zhang, Weihua and Li, Xinzhong and Scott, James and Chen, Yii-Der Ida and Burke, Gregory L and K{\"a}h{\"o}nen, Mika and Viikari, Jorma and D{\"o}ring, Angela and Meitinger, Thomas and Davies, Gail and Starr, John M and Emilsson, Valur and Plump, Andrew and Lindeman, Jan H and Hoen, Peter A C {\textquoteright}t and K{\"o}nig, Inke R and Felix, Janine F and Clarke, Robert and Hopewell, Jemma C and Ongen, Halit and Breteler, Monique and Debette, St{\'e}phanie and Destefano, Anita L and Fornage, Myriam and Mitchell, Gary F and Smith, Nicholas L and Holm, Hilma and Stefansson, Kari and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Samani, Nilesh J and Preuss, Michael and Rudan, Igor and Hayward, Caroline and Deary, Ian J and Wichmann, H-Erich and Raitakari, Olli T and Palmas, Walter and Kooner, Jaspal S and Stolk, Ronald P and Jukema, J Wouter and Wright, Alan F and Boomsma, Dorret I and Bandinelli, Stefania and Gyllensten, Ulf B and Wilson, James F and Ferrucci, Luigi and Schmidt, Reinhold and Farrall, Martin and Spector, Tim D and Palmer, Lyle J and Tuomilehto, Jaakko and Pfeufer, Arne and Gasparini, Paolo and Siscovick, David and Altshuler, David and Loos, Ruth J F and Toniolo, Daniela and Snieder, Harold and Gieger, Christian and Meneton, Pierre and Wareham, Nicholas J and Oostra, Ben A and Metspalu, Andres and Launer, Lenore and Rettig, Rainer and Strachan, David P and Beckmann, Jacques S and Witteman, Jacqueline C M and Erdmann, Jeanette and van Dijk, Ko Willems and Boerwinkle, Eric and Boehnke, Michael and Ridker, Paul M and J{\"a}rvelin, Marjo-Riitta and Chakravarti, Aravinda and Abecasis, Goncalo R and Gudnason, Vilmundur and Newton-Cheh, Christopher and Levy, Daniel and Munroe, Patricia B and Psaty, Bruce M and Caulfield, Mark J and Rao, Dabeeru C and Tobin, Martin D and Elliott, Paul and van Duijn, Cornelia M} } @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} }