@article {1206, title = {Common genetic variants associate with serum phosphorus concentration.}, journal = {J Am Soc Nephrol}, volume = {21}, year = {2010}, month = {2010 Jul}, pages = {1223-32}, abstract = {

Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR <45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P < 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation.

}, keywords = {Adult, Aged, European Continental Ancestry Group, Female, Fibroblast Growth Factors, Gene Frequency, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Kidney, Male, Middle Aged, Phosphorus, Polymorphism, Single Nucleotide, Receptors, Calcium-Sensing, Sex Factors, Sodium-Phosphate Cotransporter Proteins, Type IIa}, issn = {1533-3450}, doi = {10.1681/ASN.2009111104}, author = {Kestenbaum, Bryan and Glazer, Nicole L and K{\"o}ttgen, Anna and Felix, Janine F and Hwang, Shih-Jen and Liu, Yongmei and Lohman, Kurt and Kritchevsky, Stephen B and Hausman, Dorothy B and Petersen, Ann-Kristin and Gieger, Christian and Ried, Janina S and Meitinger, Thomas and Strom, Tim M and Wichmann, H Erich and Campbell, Harry and Hayward, Caroline and Rudan, Igor and de Boer, Ian H and Psaty, Bruce M and Rice, Kenneth M and Chen, Yii-Der Ida and Li, Man and Arking, Dan E and Boerwinkle, Eric and Coresh, Josef and Yang, Qiong and Levy, Daniel and van Rooij, Frank J A and Dehghan, Abbas and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Hofman, Albert and van Duijn, Cornelia M and Shlipak, Michael G and Kao, W H Linda and Witteman, Jacqueline C M and Siscovick, David S and Fox, Caroline S} } @article {1170, title = {Common variants in KCNN3 are associated with lone atrial fibrillation.}, journal = {Nat Genet}, volume = {42}, year = {2010}, month = {2010 Mar}, pages = {240-4}, abstract = {

Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95\% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

}, keywords = {Adolescent, Adult, Aged, Atrial Fibrillation, Case-Control Studies, Cohort Studies, Female, Genome-Wide Association Study, Humans, Introns, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Small-Conductance Calcium-Activated Potassium Channels, Young Adult}, issn = {1546-1718}, doi = {10.1038/ng.537}, author = {Ellinor, Patrick T and Lunetta, Kathryn L and Glazer, Nicole L and Pfeufer, Arne and Alonso, Alvaro and Chung, Mina K and Sinner, Moritz F and de Bakker, Paul I W and Mueller, Martina and Lubitz, Steven A and Fox, Ervin and Darbar, Dawood and Smith, Nicholas L and Smith, Jonathan D and Schnabel, Renate B and Soliman, Elsayed Z and Rice, Kenneth M and Van Wagoner, David R and Beckmann, Britt-M and van Noord, Charlotte and Wang, Ke and Ehret, Georg B and Rotter, Jerome I and Hazen, Stanley L and Steinbeck, Gerhard and Smith, Albert V and Launer, Lenore J and Harris, Tamara B and Makino, Seiko and Nelis, Mari and Milan, David J and Perz, Siegfried and Esko, T{\~o}nu and K{\"o}ttgen, Anna and Moebus, Susanne and Newton-Cheh, Christopher and Li, Man and M{\"o}hlenkamp, Stefan and Wang, Thomas J and Kao, W H Linda and Vasan, Ramachandran S and N{\"o}then, Markus M and MacRae, Calum A and Stricker, Bruno H Ch and Hofman, Albert and Uitterlinden, Andr{\'e} G and Levy, Daniel and Boerwinkle, Eric and Metspalu, Andres and Topol, Eric J and Chakravarti, Aravinda and Gudnason, Vilmundur and Psaty, Bruce M and Roden, Dan M and Meitinger, Thomas and Wichmann, H-Erich and Witteman, Jacqueline C M and Barnard, John and Arking, Dan E and Benjamin, Emelia J and Heckbert, Susan R and K{\"a}{\"a}b, Stefan} } @article {1223, title = {Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels.}, journal = {PLoS Genet}, volume = {6}, year = {2010}, month = {2010 Aug 05}, abstract = {

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using approximately 2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5 x 10(-8)) or suggestive associations (p<4 x 10(-7)) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4 x 10(-7). Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels.

}, keywords = {Adult, Aged, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Magnesium, Male, Middle Aged, Polymorphism, Single Nucleotide, Potassium, Sodium}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1001045}, author = {Meyer, Tamra E and Verwoert, Germaine C and Hwang, Shih-Jen and Glazer, Nicole L and Smith, Albert V and van Rooij, Frank J A and Ehret, Georg B and Boerwinkle, Eric and Felix, Janine F and Leak, Tennille S and Harris, Tamara B and Yang, Qiong and Dehghan, Abbas and Aspelund, Thor and Katz, Ronit and Homuth, Georg and Kocher, Thomas and Rettig, Rainer and Ried, Janina S and Gieger, Christian and Prucha, Hanna and Pfeufer, Arne and Meitinger, Thomas and Coresh, Josef and Hofman, Albert and Sarnak, Mark J and Chen, Yii-Der Ida and Uitterlinden, Andr{\'e} G and Chakravarti, Aravinda and Psaty, Bruce M and van Duijn, Cornelia M and Kao, W H Linda and Witteman, Jacqueline C M and Gudnason, Vilmundur and Siscovick, David S and Fox, Caroline S and K{\"o}ttgen, Anna} } @article {1159, title = {Genome-wide association study of PR interval.}, journal = {Nat Genet}, volume = {42}, year = {2010}, month = {2010 Feb}, pages = {153-9}, abstract = {

The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.

}, keywords = {Aged, Atrial Fibrillation, Cohort Studies, Electrocardiography, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Conduction System, Humans, Male, Meta-Analysis as Topic}, issn = {1546-1718}, doi = {10.1038/ng.517}, author = {Pfeufer, Arne and van Noord, Charlotte and Marciante, Kristin D and Arking, Dan E and Larson, Martin G and Smith, Albert Vernon and Tarasov, Kirill V and M{\"u}ller, Martina and Sotoodehnia, Nona and Sinner, Moritz F and Verwoert, Germaine C and Li, Man and Kao, W H Linda and K{\"o}ttgen, Anna and Coresh, Josef and Bis, Joshua C and Psaty, Bruce M and Rice, Kenneth and Rotter, Jerome I and Rivadeneira, Fernando and Hofman, Albert and Kors, Jan A and Stricker, Bruno H C and Uitterlinden, Andr{\'e} G and van Duijn, Cornelia M and Beckmann, Britt M and Sauter, Wiebke and Gieger, Christian and Lubitz, Steven A and Newton-Cheh, Christopher and Wang, Thomas J and Magnani, Jared W and Schnabel, Renate B and Chung, Mina K and Barnard, John and Smith, Jonathan D and Van Wagoner, David R and Vasan, Ramachandran S and Aspelund, Thor and Eiriksdottir, Gudny and Harris, Tamara B and Launer, Lenore J and Najjar, Samer S and Lakatta, Edward and Schlessinger, David and Uda, Manuela and Abecasis, Goncalo R and M{\"u}ller-Myhsok, Bertram and Ehret, Georg B and Boerwinkle, Eric and Chakravarti, Aravinda and Soliman, Elsayed Z and Lunetta, Kathryn L and Perz, Siegfried and Wichmann, H-Erich and Meitinger, Thomas and Levy, Daniel and Gudnason, Vilmundur and Ellinor, Patrick T and Sanna, Serena and K{\"a}{\"a}b, Stefan and Witteman, Jacqueline C M and Alonso, Alvaro and Benjamin, Emelia J and Heckbert, Susan R} } @article {1336, title = {Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD.}, journal = {PLoS Genet}, volume = {7}, year = {2011}, month = {2011 Sep}, pages = {e1002292}, abstract = {

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.

}, keywords = {Adaptor Proteins, Signal Transducing, Adult, Aged, Chronic Disease, Creatinine, European Continental Ancestry Group, Female, Follow-Up Studies, Genetic Association Studies, Humans, Kidney Diseases, Kidney Failure, Chronic, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptor, Epidermal Growth Factor, Uromodulin}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002292}, author = {B{\"o}ger, Carsten A and Gorski, Mathias and Li, Man and Hoffmann, Michael M and Huang, Chunmei and Yang, Qiong and Teumer, Alexander and Krane, Vera and O{\textquoteright}Seaghdha, Conall M and Kutalik, Zolt{\'a}n and Wichmann, H-Erich and Haak, Thomas and Boes, Eva and Coassin, Stefan and Coresh, Josef and Kollerits, Barbara and Haun, Margot and Paulweber, Bernhard and K{\"o}ttgen, Anna and Li, Guo and Shlipak, Michael G and Powe, Neil and Hwang, Shih-Jen and Dehghan, Abbas and Rivadeneira, Fernando and Uitterlinden, Andre and Hofman, Albert and Beckmann, Jacques S and Kr{\"a}mer, Bernhard K and Witteman, Jacqueline and Bochud, Murielle and Siscovick, David and Rettig, Rainer and Kronenberg, Florian and Wanner, Christoph and Thadhani, Ravi I and Heid, Iris M and Fox, Caroline S and Kao, W H} } @article {1327, title = {Genetic association for renal traits among participants of African ancestry reveals new loci for renal function.}, journal = {PLoS Genet}, volume = {7}, year = {2011}, month = {2011 Sep}, pages = {e1002264}, abstract = {

Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m(2)), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3{\texttimes}10(-7)) and FNDC1 (p-value = 3.0{\texttimes}10(-7)) for UACR, and KCNQ1 with eGFR (p = 3.6{\texttimes}10(-6)). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish.

}, keywords = {Adaptor Proteins, Vesicular Transport, Adult, African Continental Ancestry Group, Aged, Animals, Female, Gene Knockdown Techniques, Genetic Association Studies, Genetic Loci, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, KCNQ1 Potassium Channel, Kidney, Kidney Failure, Chronic, Male, Middle Aged, Neoplasm Proteins, Phenotype, Polymorphism, Single Nucleotide, Zebrafish}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002264}, author = {Liu, Ching-Ti and Garnaas, Maija K and Tin, Adrienne and K{\"o}ttgen, Anna and Franceschini, Nora and Peralta, Carmen A and de Boer, Ian H and Lu, Xiaoning and Atkinson, Elizabeth and Ding, Jingzhong and Nalls, Michael and Shriner, Daniel and Coresh, Josef and Kutlar, Abdullah and Bibbins-Domingo, Kirsten and Siscovick, David and Akylbekova, Ermeg and Wyatt, Sharon and Astor, Brad and Mychaleckjy, Josef and Li, Man and Reilly, Muredach P and Townsend, Raymond R and Adeyemo, Adebowale and Zonderman, Alan B and de Andrade, Mariza and Turner, Stephen T and Mosley, Thomas H and Harris, Tamara B and Rotimi, Charles N and Liu, Yongmei and Kardia, Sharon L R and Evans, Michele K and Shlipak, Michael G and Kramer, Holly and Flessner, Michael F and Dreisbach, Albert W and Goessling, Wolfram and Cupples, L Adrienne and Kao, W Linda and Fox, Caroline S} } @article {1305, title = {Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele.}, journal = {Hum Mol Genet}, volume = {20}, year = {2011}, month = {2011 Oct 15}, pages = {4056-68}, abstract = {

Serum urate concentrations are highly heritable and elevated serum urate is a key risk factor for gout. Genome-wide association studies (GWAS) of serum urate in African American (AA) populations are lacking. We conducted a meta-analysis of GWAS of serum urate levels and gout among 5820 AA and a large candidate gene study among 6890 AA and 21 708 participants of European ancestry (EA) within the Candidate Gene Association Resource Consortium. Findings were tested for replication among 1996 independent AA individuals, and evaluated for their association among 28 283 EA participants of the CHARGE Consortium. Functional studies were conducted using (14)C-urate transport assays in mammalian Chinese hamster ovary cells. In the discovery GWAS of serum urate, three loci achieved genome-wide significance (P< 5.0 {\texttimes} 10(-8)): a novel locus near SGK1/SLC2A12 on chromosome 6 (rs9321453, P= 1.0 {\texttimes} 10(-9)), and two loci previously identified in EA participants, SLC2A9 (P= 3.8 {\texttimes} 10(-32)) and SLC22A12 (P= 2.1 {\texttimes} 10(-10)). A novel rare non-synonymous variant of large effect size in SLC22A12, rs12800450 (minor allele frequency 0.01, G65W), was identified and replicated (beta -1.19 mg/dl, P= 2.7 {\texttimes} 10(-16)). (14)C-urate transport assays showed reduced urate transport for the G65W URAT1 mutant. Finally, in analyses of 11 loci previously associated with serum urate in EA individuals, 10 of 11 lead single-nucleotide polymorphisms showed direction-consistent association with urate among AA. In summary, we identified and replicated one novel locus in association with serum urate levels and experimentally characterize the novel G65W variant in URAT1 as a functional allele. Our data support the importance of multi-ethnic GWAS in the identification of novel risk loci as well as functional variants.

}, keywords = {Adult, African Americans, Aged, Animals, CHO Cells, Cricetinae, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Gout, Humans, Loss of Heterozygosity, Male, Middle Aged, Organic Anion Transporters, Organic Cation Transport Proteins, Polymorphism, Single Nucleotide, Uric Acid, Young Adult}, issn = {1460-2083}, doi = {10.1093/hmg/ddr307}, author = {Tin, Adrienne and Woodward, Owen M and Kao, Wen Hong Linda and Liu, Ching-Ti and Lu, Xiaoning and Nalls, Michael A and Shriner, Daniel and Semmo, Mariam and Akylbekova, Ermeg L and Wyatt, Sharon B and Hwang, Shih-Jen and Yang, Qiong and Zonderman, Alan B and Adeyemo, Adebowale A and Palmer, Cameron and Meng, Yan and Reilly, Muredach and Shlipak, Michael G and Siscovick, David and Evans, Michele K and Rotimi, Charles N and Flessner, Michael F and K{\"o}ttgen, Michael and Cupples, L Adrienne and Fox, Caroline S and K{\"o}ttgen, Anna} } @article {1304, title = {Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals.}, journal = {PLoS Genet}, volume = {7}, year = {2011}, month = {2011 Jun}, pages = {e1002158}, abstract = {

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8{\texttimes}10(-10)). The risk allele, while ancestral, has a frequency of ~1.4\%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95\% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).

}, keywords = {Adult, Aged, Alleles, Chromosomes, Human, Pair 2, Death, Sudden, Cardiac, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Myocardial Contraction, Polymorphism, Single Nucleotide}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002158}, author = {Arking, Dan E and Junttila, M Juhani and Goyette, Philippe and Huertas-Vazquez, Adriana and Eijgelsheim, Mark and Blom, Marieke T and Newton-Cheh, Christopher and Reinier, Kyndaron and Teodorescu, Carmen and Uy-Evanado, Audrey and Carter-Monroe, Naima and Kaikkonen, Kari S and Kortelainen, Marja-Leena and Boucher, Gabrielle and Lagac{\'e}, Caroline and Moes, Anna and Zhao, XiaoQing and Kolodgie, Frank and Rivadeneira, Fernando and Hofman, Albert and Witteman, Jacqueline C M and Uitterlinden, Andr{\'e} G and Marsman, Roos F and Pazoki, Raha and Bardai, Abdennasser and Koster, Rudolph W and Dehghan, Abbas and Hwang, Shih-Jen and Bhatnagar, Pallav and Post, Wendy and Hilton, Gina and Prineas, Ronald J and Li, Man and K{\"o}ttgen, Anna and Ehret, Georg and Boerwinkle, Eric and Coresh, Josef and Kao, W H Linda and Psaty, Bruce M and Tomaselli, Gordon F and Sotoodehnia, Nona and Siscovick, David S and Burke, Greg L and Marb{\'a}n, Eduardo and Spooner, Peter M and Cupples, L Adrienne and Jui, Jonathan and Gunson, Karen and Kesaniemi, Y Antero and Wilde, Arthur A M and Tardif, Jean-Claude and O{\textquoteright}Donnell, Christopher J and Bezzina, Connie R and Virmani, Renu and Stricker, Bruno H C H and Tan, Hanno L and Albert, Christine M and Chakravarti, Aravinda and Rioux, John D and Huikuri, Heikki V and Chugh, Sumeet S} } @article {1377, 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, Asa 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 {9002, title = {Meta-analyses identify DNA methylation associated with kidney function and damage.}, journal = {Nat Commun}, volume = {12}, year = {2021}, month = {2021 12 09}, pages = {7174}, abstract = {

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

}, keywords = {Adult, Aged, CpG Islands, DNA Methylation, Female, Glomerular Filtration Rate, Humans, Interferon Regulatory Factors, Kidney, Kidney Function Tests, LIM Domain Proteins, Male, Membrane Proteins, Middle Aged, Renal Insufficiency, Chronic, Transcription Factors}, issn = {2041-1723}, doi = {10.1038/s41467-021-27234-3}, author = {Schlosser, Pascal and Tin, Adrienne and Matias-Garcia, Pamela R and Thio, Chris H L and Joehanes, Roby and Liu, Hongbo and Weihs, Antoine and Yu, Zhi and Hoppmann, Anselm and Grundner-Culemann, Franziska and Min, Josine L and Adeyemo, Adebowale A and Agyemang, Charles and Arnl{\"o}v, Johan and Aziz, Nasir A and Baccarelli, Andrea and Bochud, Murielle and Brenner, Hermann and Breteler, Monique M B and Carmeli, Cristian and Chaker, Layal and Chambers, John C and Cole, Shelley A and Coresh, Josef and Corre, Tanguy and Correa, Adolfo and Cox, Simon R and de Klein, Niek and Delgado, Graciela E and Domingo-Relloso, Arce and Eckardt, Kai-Uwe and Ekici, Arif B and Endlich, Karlhans and Evans, Kathryn L and Floyd, James S and Fornage, Myriam and Franke, Lude and Fraszczyk, Eliza and Gao, Xu and G{\`a}o, Xin and Ghanbari, Mohsen and Ghasemi, Sahar and Gieger, Christian and Greenland, Philip and Grove, Megan L and Harris, Sarah E and Hemani, Gibran and Henneman, Peter and Herder, Christian and Horvath, Steve and Hou, Lifang and Hurme, Mikko A and Hwang, Shih-Jen and Jarvelin, Marjo-Riitta and Kardia, Sharon L R and Kasela, Silva and Kleber, Marcus E and Koenig, Wolfgang and Kooner, Jaspal S and Kramer, Holly and Kronenberg, Florian and Kuhnel, Brigitte and Lehtim{\"a}ki, Terho and Lind, Lars and Liu, Dan and Liu, Yongmei and Lloyd-Jones, Donald M and Lohman, Kurt and Lorkowski, Stefan and Lu, Ake T and Marioni, Riccardo E and M{\"a}rz, Winfried and McCartney, Daniel L and Meeks, Karlijn A C and Milani, Lili and Mishra, Pashupati P and Nauck, Matthias and Navas-Acien, Ana and Nowak, Christoph and Peters, Annette and Prokisch, Holger and Psaty, Bruce M and Raitakari, Olli T and Ratliff, Scott M and Reiner, Alex P and Rosas, Sylvia E and Sch{\"o}ttker, Ben and Schwartz, Joel and Sedaghat, Sanaz and Smith, Jennifer A and Sotoodehnia, Nona and Stocker, Hannah R and Stringhini, Silvia and Sundstr{\"o}m, Johan and Swenson, Brenton R and Tellez-Plaza, Maria and van Meurs, Joyce B J and van Vliet-Ostaptchouk, Jana V and Venema, Andrea and Verweij, Niek and Walker, Rosie M and Wielscher, Matthias and Winkelmann, Juliane and Wolffenbuttel, Bruce H R and Zhao, Wei and Zheng, Yinan and Loh, Marie and Snieder, Harold and Levy, Daniel and Waldenberger, Melanie and Susztak, Katalin and K{\"o}ttgen, Anna and Teumer, Alexander} }