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1. Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas

Author

Hughes, Odessica, Bentley, Amy R, Breeze, Charles E, Aguet, Francois, Xu, Xiaoguang, Nadkarni, Girish, Sun, Quan, Lin, Bridget M, Gilliland, Thomas, Meyer, Mariah C, Du, Jiawen, Raffield, Laura M, Kramer, Holly, Morton, Robert W, Gouveia, Mateus H, Atkinson, Elizabeth G, Valladares-Salgado, Adan, Wacher-Rodarte, Niels, Dueker, Nicole D, Guo, Xiuqing, Hai, Yang, Adeyemo, Adebowale, Best, Lyle G, Cai, Jianwen, Chen, Guanjie, Chong, Michael, Doumatey, Ayo, Eales, James, Goodarzi, Mark O, Ipp, Eli, Irvin, Marguerite Ryan, Jiang, Minzhi, Jones, Alana C, Kooperberg, Charles, Krieger, Jose E, Lange, Ethan M, Lanktree, Matthew B, Lash, James P, Lotufo, Paulo A, Loos, Ruth JF, My, Vy Thi Ha, Peralta-Romero, Jesús, Qi, Lihong, Raffel, Leslie J, Rich, Stephen S, Rodriquez, Erik J, Tarazona-Santos, Eduardo, Taylor, Kent D, Umans, Jason G, Wen, Jia, Young, Bessie A, Yu, Zhi, Zhang, Ying, Chen, Yii-Der Ida, Rundek, Tanja, Rotter, Jerome I, Cruz, Miguel, Fornage, Myriam, Lima-Costa, Maria Fernanda, Pereira, Alexandre C, Paré, Guillaume, Natarajan, Pradeep, Cole, Shelley A, Carson, April P, Lange, Leslie A, Li, Yun, Perez-Stable, Eliseo J, Do, Ron, Charchar, Fadi J, Tomaszewski, Maciej, Mychaleckyj, Josyf C, Rotimi, Charles, Morris, Andrew P, and Franceschini, Nora

Subjects
Biological Sciences, Genetics, Kidney Disease, Prevention, Human Genome, Renal and urogenital, Good Health and Well Being, Humans, Genome-Wide Association Study, Renal Insufficiency, Chronic, Glomerular Filtration Rate, Multifactorial Inheritance, Kidney, admixed populations, chronic kidney disease, eGFR, expression quantitative trait locus, fine-mapping, genome-wide association study, kidney function, multi-ancestry, polygenic scores
Abstract

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p

Published
2024

2. Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury

Author

Vlasschaert, Caitlyn, Robinson-Cohen, Cassianne, Chen, Jianchun, Akwo, Elvis, Parker, Alyssa C., Silver, Samuel A., Bhatraju, Pavan K., Poisner, Hannah, Cao, Shirong, Jiang, Ming, Wang, Yinqiu, Niu, Aolei, Siew, Edward, Van Amburg, Joseph C., Kramer, Holly J., Kottgen, Anna, Franceschini, Nora, Psaty, Bruce M., Tracy, Russell P., Alonso, Alvaro, Arking, Dan E., Coresh, Josef, Ballantyne, Christie M., Boerwinkle, Eric, Grams, Morgan, Zhang, Ming-Zhi, Kestenbaum, Bryan, Lanktree, Matthew B., Rauh, Michael J., Harris, Jr, Raymond C., and Bick, Alexander G.

Published
2024
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12. Kidney Volume and Risk of Incident Kidney Outcomes

Author

Wu, Jianhan, primary, Wang, Yifan, additional, Vlasschaert, Caitlyn, additional, Lali, Ricky, additional, Feiner, James, additional, Gaheer, Pukhraj, additional, Yang, Serena, additional, Perrot, Nicolas, additional, Chong, Michael, additional, Paré, Guillaume, additional, and Lanktree, Matthew B., additional

Published
2024
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14. Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

Köttgen, Anna, Cornec-Le Gall, Emilie, Halbritter, Jan, Kiryluk, Krzysztof, Mallett, Andrew J., Parekh, Rulan S., Rasouly, Hila Milo, Sampson, Matthew G., Tin, Adrienne, Antignac, Corinne, Ars, Elisabet, Bergmann, Carsten, Bleyer, Anthony J., Bockenhauer, Detlef, Devuyst, Olivier, Florez, Jose C., Fowler, Kevin J., Franceschini, Nora, Fukagawa, Masafumi, Gale, Daniel P., Gbadegesin, Rasheed A., Goldstein, David B., Grams, Morgan E., Greka, Anna, Gross, Oliver, Guay-Woodford, Lisa M., Harris, Peter C., Hoefele, Julia, Hung, Adriana M., Knoers, Nine V.A.M., Kopp, Jeffrey B., Kretzler, Matthias, Lanktree, Matthew B., Lipska-Ziętkiewicz, Beata S., Nicholls, Kathleen, Nozu, Kandai, Ojo, Akinlolu, Parsa, Afshin, Pattaro, Cristian, Pei, York, Pollak, Martin R., Rhee, Eugene P., Sanna-Cherchi, Simone, Savige, Judy, Sayer, John A., Scolari, Francesco, Sedor, John R., Sim, Xueling, Somlo, Stefan, Susztak, Katalin, Tayo, Bamidele O., Torra, Roser, van Eerde, Albertien M., Weinstock, André, Winkler, Cheryl A., Wuttke, Matthias, Zhang, Hong, King, Jennifer M., Cheung, Michael, Jadoul, Michel, Winkelmayer, Wolfgang C., and Gharavi, Ali G.

Published
2022
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16. Whole body resistance training on functional outcomes of patients with Stage 4 or 5 chronic kidney disease: A systematic review.

Author

Abrahim, Salma, Steele, Alexandra P., Voth, Jennifer, Krepinsky, Joan C., Lanktree, Matthew B., and Hawke, Thomas J.

Subjects
RESISTANCE training, CHRONIC kidney failure, FUNCTIONAL training, FUNCTIONAL status, SCIENTIFIC literature
Abstract

Chronic kidney disease (CKD) causes skeletal muscle wasting, resulting in reduced function and inability to live independently. This systematic review critically appraised the scientific literature regarding the effects of full‐body resistance training on clinically‐relevant functional capacity measures in CKD. The study population included studies of people with Stage 4 or 5 CKD and a mean age of 40+ years old. Eight databases were searched for eligible studies: Pubmed, Embase, Cochrane, CINAHL, Scopus, Web of Science, MEDLINE, and AGELINE. MeSH terms and keyword combinations were used for screening following the PRISMA conduct. Inclusion criteria were based on PICO principles and no date of publication filter was applied. The intervention was training 2 days/week of structured resistance exercises using major upper and lower muscle groups. Minimum intervention period was 7 weeks. Comparison groups maintained their habitual activity without structured exercise training. Outcome measures of interest were: 6‐min walk test, grip strength, timed up‐and‐go test, and sit‐to‐stand. Eight randomized controlled trials and one nonequivalent comparison‐group study fulfilled the inclusion criteria and underwent data extraction. All studies were of hemodialysis patients. The evidence indicates that full‐body resistance exercise significantly improved grip strength, timed up and go and sit to stand tests; metrics associated with enhanced quality and quantity of life. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations

Author

Franceschini, Nora, Fox, Ervin, Zhang, Zhaogong, Edwards, Todd L, Nalls, Michael A, Sung, Yun Ju, Tayo, Bamidele O, Sun, Yan V, Gottesman, Omri, Adeyemo, Adebawole, Johnson, Andrew D, Young, J Hunter, Rice, Ken, Duan, Qing, Chen, Fang, Li, Yun, Tang, Hua, Fornage, Myriam, Keene, Keith L, Andrews, Jeanette S, Smith, Jennifer A, Faul, Jessica D, Guangfa, Zhang, Guo, Wei, Liu, Yu, Murray, Sarah S, Musani, Solomon K, Srinivasan, Sathanur, Edwards, Digna R Velez, Wang, Heming, Becker, Lewis C, Bovet, Pascal, Bochud, Murielle, Broeckel, Ulrich, Burnier, Michel, Carty, Cara, Chasman, Daniel I, Ehret, Georg, Chen, Wei-Min, Chen, Guanjie, Chen, Wei, Ding, Jingzhong, Dreisbach, Albert W, Evans, Michele K, Guo, Xiuqing, Garcia, Melissa E, Jensen, Rich, Keller, Margaux F, Lettre, Guillaume, Lotay, Vaneet, Martin, Lisa W, Moore, Jason H, Morrison, Alanna C, Mosley, Thomas H, Ogunniyi, Adesola, Palmas, Walter, Papanicolaou, George, Penman, Alan, Polak, Joseph F, Ridker, Paul M, Salako, Babatunde, Singleton, Andrew B, Shriner, Daniel, Taylor, Kent D, Vasan, Ramachandran, Wiggins, Kerri, Williams, Scott M, Yanek, Lisa R, Zhao, Wei, Zonderman, Alan B, Becker, Diane M, Berenson, Gerald, Boerwinkle, Eric, Bottinger, Erwin, Cushman, Mary, Eaton, Charles, Nyberg, Fredrik, Heiss, Gerardo, Hirschhron, Joel N, Howard, Virginia J, Karczewsk, Konrad J, Lanktree, Matthew B, Liu, Kiang, Liu, Yongmei, Loos, Ruth, Margolis, Karen, Snyder, Michael, Consortium, the Asian Genetic Epidemiology Network, Go, Min Jin, Kim, Young Jin, Lee, Jong-Young, Jeon, Jae-Pil, Kim, Sung Soo, Han, Bok-Ghee, Cho, Yoon Shin, Sim, Xueling, Tay, Wan Ting, Ong, Rick Twee Hee, Seielstad, Mark, and Liu, Jian Jun

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Cardiovascular, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Africa, Black People, Blood Pressure, Cohort Studies, Databases, Genetic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Reproducibility of Results, Asian Genetic Epidemiology Network Consortium, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

Published
2013

25. Loci influencing blood pressure identified using a cardiovascular gene-centric array

Author

Ganesh, Santhi K, Tragante, Vinicius, Guo, Wei, Guo, Yiran, Lanktree, Matthew B, Smith, Erin N, Johnson, Toby, Castillo, Berta Almoguera, Barnard, John, Baumert, Jens, Chang, Yen-Pei Christy, Elbers, Clara C, Farrall, Martin, Fischer, Mary E, Franceschini, Nora, Gaunt, Tom R, Gho, Johannes MIH, Gieger, Christian, Gong, Yan, Isaacs, Aaron, Kleber, Marcus E, Leach, Irene Mateo, McDonough, Caitrin W, Meijs, Matthijs FL, Mellander, Olle, Molony, Cliona M, Nolte, Ilja M, Padmanabhan, Sandosh, Price, Tom S, Rajagopalan, Ramakrishnan, Shaffer, Jonathan, Shah, Sonia, Shen, Haiqing, Soranzo, Nicole, van der Most, Peter J, Van Iperen, Erik PA, Van Setten, Jessic A, Vonk, Judith M, Zhang, Li, Beitelshees, Amber L, Berenson, Gerald S, Bhatt, Deepak L, Boer, Jolanda MA, Boerwinkle, Eric, Burkley, Ben, Burt, Amber, Chakravarti, Aravinda, Chen, Wei, Cooper-DeHoff, Rhonda M, Curtis, Sean P, Dreisbach, Albert, Duggan, David, Ehret, Georg B, Fabsitz, Richard R, Fornage, Myriam, Fox, Ervin, Furlong, Clement E, Gansevoort, Ron T, Hofker, Marten H, Hovingh, G Kees, Kirkland, Susan A, Kottke-Marchant, Kandice, Kutlar, Abdullah, LaCroix, Andrea Z, Langaee, Taimour Y, Li, Yun R, Lin, Honghuang, Liu, Kiang, Maiwald, Steffi, Malik, Rainer, Murugesan, Gurunathan, Newton-Cheh, Christopher, O'Connell, Jeffery R, Onland-Moret, N Charlotte, Ouwehand, Willem H, Palmas, Walter, Penninx, Brenda W, Pepine, Carl J, Pettinger, Mary, Polak, Joseph F, Ramachandran, Vasan S, Ranchalis, Jane, Redline, Susan, Ridker, Paul M, Rose, Lynda M, Scharnag, Hubert, Schork, Nicholas J, Shimbo, Daichi, Shuldiner, Alan R, Srinivasan, Sathanur R, Stolk, Ronald P, Taylor, Herman A, Thorand, Barbara, Trip, Mieke D, van Duijn, Cornelia M, Verschuren, W Monique, Wijmenga, Cisca, Winkelmann, Bernhard R, Wyatt, Sharon, and Young, J Hunter

Subjects
Hypertension, Heart Disease, Human Genome, Genetics, Clinical Research, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Blood Pressure, Cardiovascular Diseases, Chromosome Mapping, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, White People, CARDIOGRAM, METASTROKE, LifeLines Cohort Study, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.

Published
2013

26. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

Author

Asselbergs, Folkert W, Guo, Yiran, van Iperen, Erik PA, Sivapalaratnam, Suthesh, Tragante, Vinicius, Lanktree, Matthew B, Lange, Leslie A, Almoguera, Berta, Appelman, Yolande E, Barnard, John, Baumert, Jens, Beitelshees, Amber L, Bhangale, Tushar R, Chen, Yii-Der Ida, Gaunt, Tom R, Gong, Yan, Hopewell, Jemma C, Johnson, Toby, Kleber, Marcus E, Langaee, Taimour Y, Li, Mingyao, Li, Yun R, Liu, Kiang, McDonough, Caitrin W, Meijs, Matthijs FL, Middelberg, Rita PS, Musunuru, Kiran, Nelson, Christopher P, O’Connell, Jeffery R, Padmanabhan, Sandosh, Pankow, James S, Pankratz, Nathan, Rafelt, Suzanne, Rajagopalan, Ramakrishnan, Romaine, Simon PR, Schork, Nicholas J, Shaffer, Jonathan, Shen, Haiqing, Smith, Erin N, Tischfield, Sam E, van der Most, Peter J, van Vliet-Ostaptchouk, Jana V, Verweij, Niek, Volcik, Kelly A, Zhang, Li, Bailey, Kent R, Bailey, Kristian M, Bauer, Florianne, Boer, Jolanda MA, Braund, Peter S, Burt, Amber, Burton, Paul R, Buxbaum, Sarah G, Chen, Wei, Cooper-DeHoff, Rhonda M, Cupples, L Adrienne, deJong, Jonas S, Delles, Christian, Duggan, David, Fornage, Myriam, Furlong, Clement E, Glazer, Nicole, Gums, John G, Hastie, Claire, Holmes, Michael V, Illig, Thomas, Kirkland, Susan A, Kivimaki, Mika, Klein, Ronald, Klein, Barbara E, Kooperberg, Charles, Kottke-Marchant, Kandice, Kumari, Meena, LaCroix, Andrea Z, Mallela, Laya, Murugesan, Gurunathan, Ordovas, Jose, Ouwehand, Willem H, Post, Wendy S, Saxena, Richa, Scharnagl, Hubert, Schreiner, Pamela J, Shah, Tina, Shields, Denis C, Shimbo, Daichi, Srinivasan, Sathanur R, Stolk, Ronald P, Swerdlow, Daniel I, Taylor, Herman A, Topol, Eric J, Toskala, Elina, van Pelt, Joost L, van Setten, Jessica, Yusuf, Salim, Whittaker, John C, Zwinderman, AH, Study, LifeLines Cohort, Anand, Sonia S, Balmforth, Anthony J, and Berenson, Gerald S

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Human Genome, Cardiovascular, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Cholesterol, HDL, Cholesterol, LDL, Female, Genome-Wide Association Study, Genotype, Humans, Lipids, Male, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Factors, Triglycerides, White People, LifeLines Cohort Study, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.

Published
2012

27. Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations

Author

Elbers, Clara C, Guo, Yiran, Tragante, Vinicius, van Iperen, Erik PA, Lanktree, Matthew B, Castillo, Berta Almoguera, Chen, Fang, Yanek, Lisa R, Wojczynski, Mary K, Li, Yun R, Ferwerda, Bart, Ballantyne, Christie M, Buxbaum, Sarah G, Chen, Yii-Der Ida, Chen, Wei-Min, Cupples, L Adrienne, Cushman, Mary, Duan, Yanan, Duggan, David, Evans, Michele K, Fernandes, Jyotika K, Fornage, Myriam, Garcia, Melissa, Garvey, W Timothy, Glazer, Nicole, Gomez, Felicia, Harris, Tamara B, Halder, Indrani, Howard, Virginia J, Keller, Margaux F, Kamboh, M Ilyas, Kooperberg, Charles, Kritchevsky, Stephen B, LaCroix, Andrea, Liu, Kiang, Liu, Yongmei, Musunuru, Kiran, Newman, Anne B, Onland-Moret, N Charlotte, Ordovas, Jose, Peter, Inga, Post, Wendy, Redline, Susan, Reis, Steven E, Saxena, Richa, Schreiner, Pamela J, Volcik, Kelly A, Wang, Xingbin, Yusuf, Salim, Zonderland, Alan B, Anand, Sonia S, Becker, Diane M, Psaty, Bruce, Rader, Daniel J, Reiner, Alex P, Rich, Stephen S, Rotter, Jerome I, Sale, Michèle M, Tsai, Michael Y, Borecki, Ingrid B, Hegele, Robert A, Kathiresan, Sekar, Nalls, Michael A, Taylor, Herman A, Hakonarson, Hakon, Sivapalaratnam, Suthesh, Asselbergs, Folkert W, Drenos, Fotios, Wilson, James G, and Keating, Brendan J

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Clinical Research, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Alleles, Asian People, Black People, Cholesterol, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Hispanic or Latino, Humans, Lipoproteins, HDL, Lipoproteins, LDL, Polymorphism, Single Nucleotide, Triglycerides, genetic variants, loci, lipid, genotyping, CD36 deficiency, General Science & Technology
Abstract

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.

Published
2012

28. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

Author

Lanktree, Matthew B, Guo, Yiran, Murtaza, Muhammed, Glessner, Joseph T, Bailey, Swneke D, Onland-Moret, N Charlotte, Lettre, Guillaume, Ongen, Halit, Rajagopalan, Ramakrishnan, Johnson, Toby, Shen, Haiqing, Nelson, Christopher P, Klopp, Norman, Baumert, Jens, Padmanabhan, Sandosh, Pankratz, Nathan, Pankow, James S, Shah, Sonia, Taylor, Kira, Barnard, John, Peters, Bas J, Maloney, Cliona M, Lobmeyer, Maximilian T, Stanton, Alice, Zafarmand, M Hadi, Romaine, Simon PR, Mehta, Amar, van Iperen, Erik PA, Gong, Yan, Price, Tom S, Smith, Erin N, Kim, Cecilia E, Li, Yun R, Asselbergs, Folkert W, Atwood, Larry D, Bailey, Kristian M, Bhatt, Deepak, Bauer, Florianne, Behr, Elijah R, Bhangale, Tushar, Boer, Jolanda MA, Boehm, Bernhard O, Bradfield, Jonathan P, Brown, Morris, Braund, Peter S, Burton, Paul R, Carty, Cara, Chandrupatla, Hareesh R, Chen, Wei, Connell, John, Dalgeorgou, Chrysoula, de Boer, Anthonius, Drenos, Fotios, Elbers, Clara C, Fang, James C, Fox, Caroline S, Frackelton, Edward C, Fuchs, Barry, Furlong, Clement E, Gibson, Quince, Gieger, Christian, Goel, Anuj, Grobbee, Diederik E, Hastie, Claire, Howard, Philip J, Huang, Guan-Hua, Johnson, W Craig, Li, Qing, Kleber, Marcus E, Klein, Barbara EK, Klein, Ronald, Kooperberg, Charles, Ky, Bonnie, LaCroix, Andrea, Lanken, Paul, Lathrop, Mark, Li, Mingyao, Marshall, Vanessa, Melander, Olle, Mentch, Frank D, Meyer, Nuala J, Monda, Keri L, Montpetit, Alexandre, Murugesan, Gurunathan, Nakayama, Karen, Nondahl, Dave, Onipinla, Abiodun, Rafelt, Suzanne, Newhouse, Stephen J, Otieno, F George, Patel, Sanjey R, Putt, Mary E, Rodriguez, Santiago, Safa, Radwan N, Sawyer, Douglas B, Schreiner, Pamela J, Simpson, Claire, Sivapalaratnam, Suthesh, Srinivasan, Sathanur R, and Suver, Christine

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adult, Black or African American, Asian People, Body Height, Cardiovascular System, Female, Gene Frequency, Genetic Heterogeneity, Genetic Loci, Genome-Wide Association Study, Hispanic or Latino, Humans, Interleukin-11, Male, Polymorphism, Single Nucleotide, Smad3 Protein, White People, Hugh Watkins on behalf of PROCARDIS, Meena Kumari on behalf of the Whitehall II Study and the WHII 50K Group, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.

Published
2011

29. Prognostic Utility of Total Kidney Volume for Chronic Kidney Disease Risk Prediction: An Observational and Mendelian Randomization Study

Author

Wu, Jianhan, primary, Wang, Yifan, additional, Vlasschaert, Caitlyn, additional, Lali, Ricky, additional, Feiner, James, additional, Gaheer, Pukhraj, additional, Yang, Serena, additional, Perrot, Nicolas, additional, Chong, Michael, additional, Lanktree, Matthew B., additional, and Paré, Guillaume, additional

Published
2023
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31. Clonal Hematopoiesis of Indeterminate Potential is Associated with Acute Kidney Injury

Author

Vlasschaert, Caitlyn, primary, Robinson-Cohen, Cassianne, additional, Kestenbaum, Bryan, additional, Silver, Samuel A, additional, Chen, Jian-Chun, additional, Akwo, Elvis, additional, Bhatraju, Pavan K., additional, Zhang, Ming-Zhi, additional, Cao, Shirong, additional, Jiang, Ming, additional, Wang, Yinqiu, additional, Niu, Aolei, additional, Siew, Edward, additional, Kramer, Holly, additional, Kottgen, Anna, additional, Franceschini, Nora, additional, Psaty, Bruce M., additional, Tracy, Russell, additional, Alonso, Alvaro, additional, Arking, Dan, additional, Coresh, Josef, additional, Ballantyne, Christie M., additional, Boerwinkle, Eric, additional, Grams, Morgan, additional, Lanktree, Matthew B, additional, Rauh, Michael J, additional, Harris, Raymond C, additional, and Bick, Alexander G, additional

Published
2023
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36. List of Contributors

Author

Ackerman, Michael J., primary, Annex, Brian H., additional, Bos, Johan Martijn, additional, Chung, Wendy K., additional, Dokun, Ayotunde O., additional, Hall, Jennifer L., additional, Hegele, Robert A., additional, Kathiresan, Sekar, additional, Kessler, Thorsten, additional, Kittner, Steven J., additional, Kraus, William E., additional, Lanktree, Matthew B., additional, Li, Josephine H., additional, Mitchell, Braxton D., additional, Munroe, Patricia B., additional, Orlando, Lori A., additional, Podgoreanu, Mihai V., additional, Rader, Daniel J., additional, Roden, Dan M., additional, Rosenberg, Steven, additional, Ruff, Christian T., additional, Sabatine, Marc S., additional, Schunkert, Heribert, additional, von Ameln, Simon, additional, Voora, Deepak, additional, Warren, Helen R., additional, Wingrove, James A., additional, and Wu, Rebekah R., additional

Published
2018
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38. Identifying gene–gene interactions that are highly associated with four quantitative lipid traits across multiple cohorts

Author

De, Rishika, Verma, Shefali S., Holzinger, Emily, Hall, Molly, Burt, Amber, Carrell, David S., Crosslin, David R., Jarvik, Gail P., Kuivaniemi, Helena, Kullo, Iftikhar J., Lange, Leslie A., Lanktree, Matthew B., Larson, Eric B., North, Kari E., Reiner, Alex P., Tragante, Vinicius, Tromp, Gerard, Wilson, James G., Asselbergs, Folkert W., Drenos, Fotios, Moore, Jason H., Ritchie, Marylyn D., Keating, Brendan, and Gilbert-Diamond, Diane

Published
2017
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40. A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic datasets

Author

Vlasschaert, Caitlyn, primary, Mack, Taralynn, additional, Heimlich, J. Brett, additional, Niroula, Abhishek, additional, Uddin, Mesbah, additional, Weinstock, Joshua, additional, Sharber, Brian, additional, Silver, Alexander J., additional, Xu, Yaomin, additional, Savona, Michael, additional, Gibson, Christopher, additional, Lanktree, Matthew B., additional, Rauh, Michael J., additional, Ebert, Benjamin L., additional, Natarajan, Pradeep, additional, Jaiswal, Siddhartha, additional, and Bick, Alexander G., additional

Published
2022
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41. Clonal Hematopoiesis of Indeterminate Potential and Kidney Function Decline in the General Population

Author

Kestenbaum, Bryan, primary, Bick, Alexander G., additional, Vlasschaert, Caitlyn, additional, Rauh, Michael J., additional, Lanktree, Matthew B., additional, Franceschini, Nora, additional, Shoemaker, Moore B., additional, Harris, Raymond C., additional, Psaty, Bruce M., additional, Köttgen, Anna, additional, Natarajan, Pradeep, additional, and Robinson-Cohen, Cassianne, additional

Published
2022
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42. Association between alcohol and cardiovascular disease : Mendelian randomisation analysis based on individual participant data

Author

IMPROVE study group, The InterAct Consortium, Holmes, Michael V, Dale, Caroline E, Zuccolo, Luisa, Silverwood, Richard J, Guo, Yiran, Ye, Zheng, Prieto-Merino, David, Dehghan, Abbas, Trompet, Stella, Wong, Andrew, Cavadino, Alana, Drogan, Dagmar, Padmanabhan, Sandosh, Li, Shanshan, Yesupriya, Ajay, Leusink, Maarten, Sundstrom, Johan, Hubacek, Jaroslav A, Pikhart, Hynek, Swerdlow, Daniel I, Panayiotou, Andrie G, Borinskaya, Svetlana A, Finan, Chris, Shah, Sonia, Kuchenbaecker, Karoline B, Shah, Tina, Engmann, Jorgen, Folkersen, Lasse, Eriksson, Per, Ricceri, Fulvio, Melander, Olle, Sacerdote, Carlotta, Gamble, Dale M, Rayaprolu, Sruti, Ross, Owen A, McLachlan, Stela, Vikhireva, Olga, Sluijs, Ivonne, Scott, Robert A, Adamkova, Vera, Flicker, Leon, van Bockxmeer, Frank M, Power, Christine, Marques-Vidal, Pedro, Meade, Tom, Marmot, Michael G, Ferro, Jose M, Paulos-Pinheiro, Sofia, Humphries, Steve E, Talmud, Philippa J, Leach, Irene Mateo, Verweij, Niek, Linneberg, Allan, Skaaby, Tea, Doevendans, Pieter A, Cramer, Maarten J, van der Harst, Pim, Klungel, Olaf H, Dowling, Nicole F, Dominiczak, Anna F, Kumari, Meena, Nicolaides, Andrew N, Weikert, Cornelia, Boeing, Heiner, Ebrahim, Shah, Gaunt, Tom R, Price, Jackie F, Lannfelt, Lars, Peasey, Anne, Kubinova, Ruzena, Pajak, Andrzej, Malyutina, Sofia, Voevoda, Mikhail I, Tamosiunas, Abdonas, Maitland-vanderZee, Anke H, Norman, Paul E, Hankey, Graeme J, Bergmann, Manuela M, Hofman, Albert, Franco, Oscar H, Cooper, Jackie, Palmen, Jutta, Spiering, Wilko, de Jong, Pim A, Kuh, Diana, Hardy, Rebecca, Uitterlinden, Andre G, Ikram, M Arfan, Ford, Ian, Hyppönen, Elina, Almeida, Osvaldo P, Wareham, Nicholas J, Khaw, Kay-Tee, Hamsten, Anders, Husemoen, Lise Lotte N, Tjønneland, Anne, Tolstrup, Janne S, Rimm, Eric, Beulens, Joline W J, Verschuren, W M Monique, Onland-Moret, N Charlotte, Hofker, Marten H, Wannamethee, S Goya, Whincup, Peter H, Morris, Richard, Vicente, Astrid M, Watkins, Hugh, Farrall, Martin, Jukema, J Wouter, Meschia, James, Cupples, L Adrienne, Sharp, Stephen J, Fornage, Myriam, Kooperberg, Charles, LaCroix, Andrea Z, Dai, James Y, Lanktree, Matthew B, Siscovick, David S, Jorgenson, Eric, Spring, Bonnie, Coresh, Josef, Li, Yun R, Buxbaum, Sarah G, Schreiner, Pamela J, Curtis, R, Y Tsai, Michael, Patel, Sanjay R, Redline, Susan, Johnson, Andrew D, Hoogeveen, Ron C, Hakonarson, Hakon, Rotter, Jerome I, Boerwinkle, Eric, de Bakker, Paul I W, Kivimaki, Mika, Asselbergs, Folkert W, Sattar, Naveed, Lawlor, Debbie A, Whittaker, John, Smith, George Davey, Mukamal, Kenneth, Psaty, Bruce M, Wilson, James G, Lange, Leslie A, Hamidovic, Ajna, Hingorani, Aroon D, Nordestgaard, Børge G, Bobak, Martin, Leon, David A, Langenberg, Claudia, Palmer, Tom M, Reiner, Alex P, Keating, Brendan J, Dudbridge, Frank, and Casas, Juan P

Published
2014

43. List of Contributors

Author

Assimes, Themistocles L., primary, Billatos, Ehab, additional, Bregendahl, Maria Esperanza, additional, Chahrour, Maria, additional, Conran, Carly, additional, Croteau-Chonka, Damien C., additional, Florez, Jose C., additional, Gesthalter, Yaron B., additional, Haga, Susanne B., additional, Hegele, Robert A., additional, Hicks, J. Kevin, additional, Jenkins, Jean, additional, Johnson, Samuel G., additional, Kathuria, Hasmeena, additional, Kuiper, Roland P., additional, Lanktree, Matthew B., additional, Liu, Wennuan, additional, Marcom, Paul K., additional, McGeachie, Michael J., additional, McLeod, Howard L., additional, Morgan, Thomas, additional, Munroe, Patricia B., additional, Na, Rong, additional, Orlando, Lori A., additional, Palaniappan, Latha, additional, Patel, Keyur, additional, Rodriguez, Laura Lyman, additional, Saxena, Akanksha, additional, Shackel, Nicholas A., additional, Tu, Thomas, additional, Udler, Miriam S., additional, van Kessel, Ad Geurts, additional, Warren, Helen R., additional, Weiss, Scott T., additional, Weren, Robbert D.A., additional, and Xu, Jianfeng, additional

Published
2017
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47. Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Köttgen, Anna, Cornec-Le Gall, Emilie, Halbritter, Jan, Kiryluk, Krzysztof, Mallett, Andrew J., Parekh, Rulan S., Rasouly, Hila Milo, Sampson, Matthew G., Tin, Adrienne, Antignac, Corinne, Ars, Elisabet, Bergmann, Carsten, Bleyer, Anthony J., Bockenhauer, Detlef, Devuyst, Olivier, Florez, Jose C., Fowler, Kevin J., Franceschini, Nora, Fukagawa, Masafumi, Gale, Daniel P., Gbadegesin, Rasheed A., Goldstein, David B., Grams, Morgan E., Greka, Anna, Gross, Oliver, Guay-Woodford, Lisa M., Harris, Peter C., Hoefele, Julia, Hung, Adriana M., Knoers, Nine V.A.M., Kopp, Jeffrey B., Kretzler, Matthias, Lanktree, Matthew B., Lipska-Ziętkiewicz, Beata S., Nicholls, Kathleen, Nozu, Kandai, Ojo, Akinlolu, Parsa, Afshin, Pattaro, Cristian, Pei, York, Pollak, Martin R., Rhee, Eugene P., Sanna-Cherchi, Simone, Savige, Judy, Sayer, John A., Scolari, Francesco, Sedor, John R., Sim, Xueling, Somlo, Stefan, Susztak, Katalin, Tayo, Bamidele O., Torra, Roser, van Eerde, Albertien M., Weinstock, André, Winkler, Cheryl A., Wuttke, Matthias, Zhang, Hong, King, Jennifer M., Cheung, Michael, Jadoul, Michel, Winkelmayer, Wolfgang C., Gharavi, Ali G., UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Köttgen, Anna, Cornec-Le Gall, Emilie, Halbritter, Jan, Kiryluk, Krzysztof, Mallett, Andrew J., Parekh, Rulan S., Rasouly, Hila Milo, Sampson, Matthew G., Tin, Adrienne, Antignac, Corinne, Ars, Elisabet, Bergmann, Carsten, Bleyer, Anthony J., Bockenhauer, Detlef, Devuyst, Olivier, Florez, Jose C., Fowler, Kevin J., Franceschini, Nora, Fukagawa, Masafumi, Gale, Daniel P., Gbadegesin, Rasheed A., Goldstein, David B., Grams, Morgan E., Greka, Anna, Gross, Oliver, Guay-Woodford, Lisa M., Harris, Peter C., Hoefele, Julia, Hung, Adriana M., Knoers, Nine V.A.M., Kopp, Jeffrey B., Kretzler, Matthias, Lanktree, Matthew B., Lipska-Ziętkiewicz, Beata S., Nicholls, Kathleen, Nozu, Kandai, Ojo, Akinlolu, Parsa, Afshin, Pattaro, Cristian, Pei, York, Pollak, Martin R., Rhee, Eugene P., Sanna-Cherchi, Simone, Savige, Judy, Sayer, John A., Scolari, Francesco, Sedor, John R., Sim, Xueling, Somlo, Stefan, Susztak, Katalin, Tayo, Bamidele O., Torra, Roser, van Eerde, Albertien M., Weinstock, André, Winkler, Cheryl A., Wuttke, Matthias, Zhang, Hong, King, Jennifer M., Cheung, Michael, Jadoul, Michel, Winkelmayer, Wolfgang C., and Gharavi, Ali G.

Published
2022

50. Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease

Author

Vlasschaert, Caitlyn, primary, McNaughton, Amy J.M., additional, Chong, Michael, additional, Cook, Elina K., additional, Hopman, Wilma, additional, Kestenbaum, Bryan, additional, Robinson-Cohen, Cassianne, additional, Garland, Jocelyn, additional, Moran, Sarah M., additional, Paré, Guillaume, additional, Clase, Catherine M., additional, Tang, Mila, additional, Levin, Adeera, additional, Holden, Rachel, additional, Rauh, Michael J., additional, and Lanktree, Matthew B., additional

Published
2022
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