Nora Franceschini1, Karin Haack, Laura Almasy, Sandra Laston, Elisa T Lee, Lyle G Best, Richard R Fabsitz, Jean W MacCluer, Barbara V Howard, Jason G Umans, Shelley A Cole. 1. Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina;, †Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas;, ‡Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma;, §Missouri Breaks Industries Research, Inc., Timber Lake, South Dakota;, ‖Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, Maryland;, ¶MedStar Health Research Institute, Hyattsville, Maryland, *Georgetown and Howard Universities Center for Clinical and Translational Science, Washington, DC.
Abstract
BACKGROUND AND OBJECTIVES: CKD disproportionally affects American Indians, who similar to other populations, show genetic susceptibility to kidney outcomes. Recent studies have identified several loci associated with kidney traits, but their relevance in American Indians is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study used data from a large, family-based genetic study of American Indians (the Strong Heart Family Study), which includes 94 multigenerational families enrolled from communities located in Oklahoma, the Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a population-based study of cardiovascular disease in American Indians. This study selected 25 single nucleotide polymorphisms in 23 loci identified from recently published kidney-related genome-wide association studies in individuals of European ancestry to evaluate their associations with kidney function (estimated GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study. This study also examined the association of single nucleotide polymorphisms in the APOL1 region with estimated GFR in 1121 Strong Heart Family Study participants. GFR was estimated using the abbreviated Modification of Diet in Renal Disease Equation. Additive genetic models adjusted for age and sex were used. RESULTS: This study identified significant associations of single nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2, PIP5K1B, and WDR72 (P<2.1 × 10(-3) to account for multiple testing). Single nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total variance and 2.9% of its heritability. An intronic variant of BCAS3 was significantly associated with urinary albumin to creatinine ratio. APOL1 single nucleotide polymorphisms were not associated with estimated GFR in a single variant test or haplotype analyses, and the at-risk variants identified in individuals with African ancestry were not detected in DNA sequencing of American Indians. CONCLUSION: This study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries.
BACKGROUND AND OBJECTIVES: CKD disproportionally affects American Indians, who similar to other populations, show genetic susceptibility to kidney outcomes. Recent studies have identified several loci associated with kidney traits, but their relevance in American Indians is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study used data from a large, family-based genetic study of American Indians (the Strong Heart Family Study), which includes 94 multigenerational families enrolled from communities located in Oklahoma, the Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a population-based study of cardiovascular disease in American Indians. This study selected 25 single nucleotide polymorphisms in 23 loci identified from recently published kidney-related genome-wide association studies in individuals of European ancestry to evaluate their associations with kidney function (estimated GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study. This study also examined the association of single nucleotide polymorphisms in the APOL1 region with estimated GFR in 1121 Strong Heart Family Study participants. GFR was estimated using the abbreviated Modification of Diet in Renal Disease Equation. Additive genetic models adjusted for age and sex were used. RESULTS: This study identified significant associations of single nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2, PIP5K1B, and WDR72 (P<2.1 × 10(-3) to account for multiple testing). Single nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total variance and 2.9% of its heritability. An intronic variant of BCAS3 was significantly associated with urinary albumin to creatinine ratio. APOL1 single nucleotide polymorphisms were not associated with estimated GFR in a single variant test or haplotype analyses, and the at-risk variants identified in individuals with African ancestry were not detected in DNA sequencing of American Indians. CONCLUSION: This study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries.
Authors: William M McClellan; David G Warnock; Suzanne Judd; Paul Muntner; Rachel E Patzer; Brian D Bradbury; Leslie A McClure; Britt B Newsome; George Howard Journal: Am J Kidney Dis Date: 2011-11-10 Impact factor: 8.860
Authors: Daniel I Chasman; Christian Fuchsberger; Cristian Pattaro; Alexander Teumer; Carsten A Böger; Karlhans Endlich; Matthias Olden; Ming-Huei Chen; Adrienne Tin; Daniel Taliun; Man Li; Xiaoyi Gao; Mathias Gorski; Qiong Yang; Claudia Hundertmark; Meredith C Foster; Conall M O'Seaghdha; Nicole Glazer; Aaron Isaacs; Ching-Ti Liu; Albert V Smith; Jeffrey R O'Connell; Maksim Struchalin; Toshiko Tanaka; Guo Li; Andrew D Johnson; Hinco J Gierman; Mary F Feitosa; Shih-Jen Hwang; Elizabeth J Atkinson; Kurt Lohman; Marilyn C Cornelis; Asa Johansson; Anke Tönjes; Abbas Dehghan; Jean-Charles Lambert; Elizabeth G Holliday; Rossella Sorice; Zoltan Kutalik; Terho Lehtimäki; Tõnu Esko; Harshal Deshmukh; Sheila Ulivi; Audrey Y Chu; Federico Murgia; Stella Trompet; Medea Imboden; Stefan Coassin; Giorgio Pistis; Tamara B Harris; Lenore J Launer; Thor Aspelund; Gudny Eiriksdottir; Braxton D Mitchell; Eric Boerwinkle; Helena Schmidt; Margherita Cavalieri; Madhumathi Rao; Frank Hu; Ayse Demirkan; Ben A Oostra; Mariza de Andrade; Stephen T Turner; Jingzhong Ding; Jeanette S Andrews; Barry I Freedman; Franco Giulianini; Wolfgang Koenig; Thomas Illig; Christa Meisinger; Christian Gieger; Lina Zgaga; Tatijana Zemunik; Mladen Boban; Cosetta Minelli; Heather E Wheeler; Wilmar Igl; Ghazal Zaboli; Sarah H Wild; Alan F Wright; Harry Campbell; David Ellinghaus; Ute Nöthlings; Gunnar Jacobs; Reiner Biffar; Florian Ernst; Georg Homuth; Heyo K Kroemer; Matthias Nauck; Sylvia Stracke; Uwe Völker; Henry Völzke; Peter Kovacs; Michael Stumvoll; Reedik Mägi; Albert Hofman; Andre G Uitterlinden; Fernando Rivadeneira; Yurii S Aulchenko; Ozren Polasek; Nick Hastie; Veronique Vitart; Catherine Helmer; Jie Jin Wang; Bénédicte Stengel; Daniela Ruggiero; Sven Bergmann; Mika Kähönen; Jorma Viikari; Tiit Nikopensius; Michael Province; Shamika Ketkar; Helen Colhoun; Alex Doney; Antonietta Robino; Bernhard K Krämer; Laura Portas; Ian Ford; Brendan M Buckley; Martin Adam; Gian-Andri Thun; Bernhard Paulweber; Margot Haun; Cinzia Sala; Paul Mitchell; Marina Ciullo; Stuart K Kim; Peter Vollenweider; Olli Raitakari; Andres Metspalu; Colin Palmer; Paolo Gasparini; Mario Pirastu; J Wouter Jukema; Nicole M Probst-Hensch; Florian Kronenberg; Daniela Toniolo; Vilmundur Gudnason; Alan R Shuldiner; Josef Coresh; Reinhold Schmidt; Luigi Ferrucci; David S Siscovick; Cornelia M van Duijn; Ingrid B Borecki; Sharon L R Kardia; Yongmei Liu; Gary C Curhan; Igor Rudan; Ulf Gyllensten; James F Wilson; Andre Franke; Peter P Pramstaller; Rainer Rettig; Inga Prokopenko; Jacqueline Witteman; Caroline Hayward; Paul M Ridker; Afshin Parsa; Murielle Bochud; Iris M Heid; W H Linda Kao; Caroline S Fox; Anna Köttgen Journal: Hum Mol Genet Date: 2012-09-08 Impact factor: 6.150
Authors: Christine A Stidley; Vallabh O Shah; Andrew S Narva; Diane Dalton; Jean W MacCluer; Arlene Bobelu; Marina Scavini; Thomas K Welty; Philip G Zager Journal: Am J Kidney Dis Date: 2002-02 Impact factor: 8.860
Authors: Carsten A Böger; Mathias Gorski; Man Li; Michael M Hoffmann; Chunmei Huang; Qiong Yang; Alexander Teumer; Vera Krane; Conall M O'Seaghdha; Zoltán Kutalik; H-Erich Wichmann; Thomas Haak; Eva Boes; Stefan Coassin; Josef Coresh; Barbara Kollerits; Margot Haun; Bernhard Paulweber; Anna Köttgen; Guo Li; Michael G Shlipak; Neil Powe; Shih-Jen Hwang; Abbas Dehghan; Fernando Rivadeneira; André Uitterlinden; Albert Hofman; Jacques S Beckmann; Bernhard K Krämer; Jacqueline Witteman; Murielle Bochud; David Siscovick; Rainer Rettig; Florian Kronenberg; Christoph Wanner; Ravi I Thadhani; Iris M Heid; Caroline S Fox; W H Kao Journal: PLoS Genet Date: 2011-09-29 Impact factor: 5.917
Authors: Cristian Pattaro; Anna Köttgen; Alexander Teumer; Maija Garnaas; Carsten A Böger; Christian Fuchsberger; Matthias Olden; Ming-Huei Chen; Adrienne Tin; Daniel Taliun; Man Li; Xiaoyi Gao; Mathias Gorski; Qiong Yang; Claudia Hundertmark; Meredith C Foster; Conall M O'Seaghdha; Nicole Glazer; Aaron Isaacs; Ching-Ti Liu; Albert V Smith; Jeffrey R O'Connell; Maksim Struchalin; Toshiko Tanaka; Guo Li; Andrew D Johnson; Hinco J Gierman; Mary Feitosa; Shih-Jen Hwang; Elizabeth J Atkinson; Kurt Lohman; Marilyn C Cornelis; Åsa Johansson; Anke Tönjes; Abbas Dehghan; Vincent Chouraki; Elizabeth G Holliday; Rossella Sorice; Zoltan Kutalik; Terho Lehtimäki; Tõnu Esko; Harshal Deshmukh; Sheila Ulivi; Audrey Y Chu; Federico Murgia; Stella Trompet; Medea Imboden; Barbara Kollerits; Giorgio Pistis; Tamara B Harris; Lenore J Launer; Thor Aspelund; Gudny Eiriksdottir; Braxton D Mitchell; Eric Boerwinkle; Helena Schmidt; Margherita Cavalieri; Madhumathi Rao; Frank B Hu; Ayse Demirkan; Ben A Oostra; Mariza de Andrade; Stephen T Turner; Jingzhong Ding; Jeanette S Andrews; Barry I Freedman; Wolfgang Koenig; Thomas Illig; Angela Döring; H-Erich Wichmann; Ivana Kolcic; Tatijana Zemunik; Mladen Boban; Cosetta Minelli; Heather E Wheeler; Wilmar Igl; Ghazal Zaboli; Sarah H Wild; Alan F Wright; Harry Campbell; David Ellinghaus; Ute Nöthlings; Gunnar Jacobs; Reiner Biffar; Karlhans Endlich; Florian Ernst; Georg Homuth; Heyo K Kroemer; Matthias Nauck; Sylvia Stracke; Uwe Völker; Henry Völzke; Peter Kovacs; Michael Stumvoll; Reedik Mägi; Albert Hofman; Andre G Uitterlinden; Fernando Rivadeneira; Yurii S Aulchenko; Ozren Polasek; Nick Hastie; Veronique Vitart; Catherine Helmer; Jie Jin Wang; Daniela Ruggiero; Sven Bergmann; Mika Kähönen; Jorma Viikari; Tiit Nikopensius; Michael Province; Shamika Ketkar; Helen Colhoun; Alex Doney; Antonietta Robino; Franco Giulianini; Bernhard K Krämer; Laura Portas; Ian Ford; Brendan M Buckley; Martin Adam; Gian-Andri Thun; Bernhard Paulweber; Margot Haun; Cinzia Sala; Marie Metzger; Paul Mitchell; Marina Ciullo; Stuart K Kim; Peter Vollenweider; Olli Raitakari; Andres Metspalu; Colin Palmer; Paolo Gasparini; Mario Pirastu; J Wouter Jukema; Nicole M Probst-Hensch; Florian Kronenberg; Daniela Toniolo; Vilmundur Gudnason; Alan R Shuldiner; Josef Coresh; Reinhold Schmidt; Luigi Ferrucci; David S Siscovick; Cornelia M van Duijn; Ingrid Borecki; Sharon L R Kardia; Yongmei Liu; Gary C Curhan; Igor Rudan; Ulf Gyllensten; James F Wilson; Andre Franke; Peter P Pramstaller; Rainer Rettig; Inga Prokopenko; Jacqueline C M Witteman; Caroline Hayward; Paul Ridker; Afshin Parsa; Murielle Bochud; Iris M Heid; Wolfram Goessling; Daniel I Chasman; W H Linda Kao; Caroline S Fox Journal: PLoS Genet Date: 2012-03-29 Impact factor: 5.917
Authors: Carsten A Böger; Ming-Huei Chen; Adrienne Tin; Matthias Olden; Anna Köttgen; Ian H de Boer; Christian Fuchsberger; Conall M O'Seaghdha; Cristian Pattaro; Alexander Teumer; Ching-Ti Liu; Nicole L Glazer; Man Li; Jeffrey R O'Connell; Toshiko Tanaka; Carmen A Peralta; Zoltán Kutalik; Jian'an Luan; Jing Hua Zhao; Shih-Jen Hwang; Ermeg Akylbekova; Holly Kramer; Pim van der Harst; Albert V Smith; Kurt Lohman; Mariza de Andrade; Caroline Hayward; Barbara Kollerits; Anke Tönjes; Thor Aspelund; Erik Ingelsson; Gudny Eiriksdottir; Lenore J Launer; Tamara B Harris; Alan R Shuldiner; Braxton D Mitchell; Dan E Arking; Nora Franceschini; Eric Boerwinkle; Josephine Egan; Dena Hernandez; Muredach Reilly; Raymond R Townsend; Thomas Lumley; David S Siscovick; Bruce M Psaty; Bryan Kestenbaum; Talin Haritunians; Sven Bergmann; Peter Vollenweider; Gerard Waeber; Vincent Mooser; Dawn Waterworth; Andrew D Johnson; Jose C Florez; James B Meigs; Xiaoning Lu; Stephen T Turner; Elizabeth J Atkinson; Tennille S Leak; Knut Aasarød; Frank Skorpen; Ann-Christine Syvänen; Thomas Illig; Jens Baumert; Wolfgang Koenig; Bernhard K Krämer; Olivier Devuyst; Josyf C Mychaleckyj; Cosetta Minelli; Stephan J L Bakker; Lyudmyla Kedenko; Bernhard Paulweber; Stefan Coassin; Karlhans Endlich; Heyo K Kroemer; Reiner Biffar; Sylvia Stracke; Henry Völzke; Michael Stumvoll; Reedik Mägi; Harry Campbell; Veronique Vitart; Nicholas D Hastie; Vilmundur Gudnason; Sharon L R Kardia; Yongmei Liu; Ozren Polasek; Gary Curhan; Florian Kronenberg; Inga Prokopenko; Igor Rudan; Johan Arnlöv; Stein Hallan; Gerjan Navis; Afshin Parsa; Luigi Ferrucci; Josef Coresh; Michael G Shlipak; Shelley B Bull; Nicholas J Paterson; H-Erich Wichmann; Nicholas J Wareham; Ruth J F Loos; Jerome I Rotter; Peter P Pramstaller; L Adrienne Cupples; Jacques S Beckmann; Qiong Yang; Iris M Heid; Rainer Rettig; Albert W Dreisbach; Murielle Bochud; Caroline S Fox; W H L Kao Journal: J Am Soc Nephrol Date: 2011-03 Impact factor: 14.978
Authors: H Zhang; M Koruyucu; F Seymen; Y Kasimoglu; J-W Kim; S Tinawi; C Zhang; M L Jacquemont; A R Vieira; J P Simmer; J C C Hu Journal: J Dent Res Date: 2019-02-19 Impact factor: 6.116
Authors: Gisele Vajgel; Suelen Cristina Lima; Diego Jeronimo S Santana; Camila B L Oliveira; Denise Maria N Costa; Pamela J Hicks; Maria Alina G M Cavalcante; Carl D Langefeld; Lucila Maria Valente; Sergio Crovella; Gianna Mastroianni Kirsztajn; Barry I Freedman; Paula Sandrin-Garcia Journal: J Rheumatol Date: 2019-11-15 Impact factor: 4.666
Authors: K A Katsura; J A Horst; D Chandra; T Q Le; Y Nakano; Y Zhang; O V Horst; L Zhu; M H Le; P K DenBesten Journal: Matrix Biol Date: 2014-07-04 Impact factor: 11.583
Authors: Tess Pallister; Amy Jennings; Robert P Mohney; Darioush Yarand; Massimo Mangino; Aedin Cassidy; Alexander MacGregor; Tim D Spector; Cristina Menni Journal: PLoS One Date: 2016-06-29 Impact factor: 3.240
Authors: Tilman Jobst-Schwan; Verena Klämbt; Maureen Tarsio; John F Heneghan; Amar J Majmundar; Shirlee Shril; Florian Buerger; Isabel Ottlewski; Boris E Shmukler; Rezan Topaloglu; Seema Hashmi; Farkhanda Hafeez; Francesco Emma; Marcella Greco; Guido F Laube; Hanan M Fathy; Martin Pohl; Jutta Gellermann; Danko Milosevic; Michelle A Baum; Shrikant Mane; Richard P Lifton; Patricia M Kane; Seth L Alper; Friedhelm Hildebrandt Journal: Kidney Int Date: 2019-10-22 Impact factor: 10.612
Authors: Sudha K Iyengar; John R Sedor; Barry I Freedman; W H Linda Kao; Matthias Kretzler; Benjamin J Keller; Hanna E Abboud; Sharon G Adler; Lyle G Best; Donald W Bowden; Allison Burlock; Yii-Der Ida Chen; Shelley A Cole; Mary E Comeau; Jeffrey M Curtis; Jasmin Divers; Christiane Drechsler; Ravi Duggirala; Robert C Elston; Xiuqing Guo; Huateng Huang; Michael Marcus Hoffmann; Barbara V Howard; Eli Ipp; Paul L Kimmel; Michael J Klag; William C Knowler; Orly F Kohn; Tennille S Leak; David J Leehey; Man Li; Alka Malhotra; Winfried März; Viji Nair; Robert G Nelson; Susanne B Nicholas; Stephen J O'Brien; Madeleine V Pahl; Rulan S Parekh; Marcus G Pezzolesi; Rebekah S Rasooly; Charles N Rotimi; Jerome I Rotter; Jeffrey R Schelling; Michael F Seldin; Vallabh O Shah; Adam M Smiles; Michael W Smith; Kent D Taylor; Farook Thameem; Denyse P Thornley-Brown; Barbara J Truitt; Christoph Wanner; E Jennifer Weil; Cheryl A Winkler; Philip G Zager; Robert P Igo; Robert L Hanson; Carl D Langefeld Journal: PLoS Genet Date: 2015-08-25 Impact factor: 5.917
Authors: Shih-Kai Wang; Yuanyuan Hu; Jie Yang; Charles E Smith; Stephanie M Nunez; Amelia S Richardson; Soumya Pal; Andrew C Samann; Jan C-C Hu; James P Simmer Journal: Mol Genet Genomic Med Date: 2015-03-29 Impact factor: 2.183