Youfang Liu1,2, Michelle S Yau3,4, Laura M Yerges-Armstrong1,2, David J Duggan1,2, Jordan B Renner1,2, Marc C Hochberg1,2, Braxton D Mitchell1,2, Rebecca D Jackson1,2, Joanne M Jordan1,2. 1. From the Thurston Arthritis Research Center, and the Department of Radiology, and the Departments of Medicine and Orthopaedics, University of North Carolina, Chapel Hill, North Carolina; Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine; Medical Care Clinical Center, Veterans Affairs Maryland Health Care System; Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Baltimore, Maryland; Institute for Aging Research, Hebrew SeniorLife; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; Translational Genomics Research Institute, Phoenix, Arizona; Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA. 2. Y. Liu, PhD, Thurston Arthritis Research Center, University of North Carolina; M.S. Yau, PhD, MPH, Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, and the Institute for Aging Research, Hebrew SeniorLife, and the Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School; L.M. Yerges-Armstrong, PhD, Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine; D.J. Duggan, PhD, Translational Genomics Research Institute; J.B. Renner, MD, Thurston Arthritis Research Center, and the Department of Radiology, University of North Carolina; M.C. Hochberg, MD, MPH, Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, and the Medical Care Clinical Center, Veterans Affairs Maryland Health Care System, and the Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center; B.D. Mitchell, PhD, MPH, Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center; R.D. Jackson, MD, Department of Internal Medicine, Ohio State University; J.M. Jordan, MD, MPH, Thurston Arthritis Research Center, University of North Carolina, and Departments of Medicine and Orthopaedics, University of North Carolina. 3. From the Thurston Arthritis Research Center, and the Department of Radiology, and the Departments of Medicine and Orthopaedics, University of North Carolina, Chapel Hill, North Carolina; Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine; Medical Care Clinical Center, Veterans Affairs Maryland Health Care System; Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Baltimore, Maryland; Institute for Aging Research, Hebrew SeniorLife; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; Translational Genomics Research Institute, Phoenix, Arizona; Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA. michelleyau@hsl.harvard.edu. 4. Y. Liu, PhD, Thurston Arthritis Research Center, University of North Carolina; M.S. Yau, PhD, MPH, Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, and the Institute for Aging Research, Hebrew SeniorLife, and the Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School; L.M. Yerges-Armstrong, PhD, Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine; D.J. Duggan, PhD, Translational Genomics Research Institute; J.B. Renner, MD, Thurston Arthritis Research Center, and the Department of Radiology, University of North Carolina; M.C. Hochberg, MD, MPH, Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, and the Medical Care Clinical Center, Veterans Affairs Maryland Health Care System, and the Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center; B.D. Mitchell, PhD, MPH, Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center; R.D. Jackson, MD, Department of Internal Medicine, Ohio State University; J.M. Jordan, MD, MPH, Thurston Arthritis Research Center, University of North Carolina, and Departments of Medicine and Orthopaedics, University of North Carolina. michelleyau@hsl.harvard.edu.
Abstract
OBJECTIVE: The etiology of knee osteoarthritis (OA), the most common form of arthritis, is complex and may differ by race or ethnicity. In recent years, genetic studies have identified many genetic variants associated with OA, but nearly all the studies were conducted in European whites and Asian Americans. Few studies have focused on the genetics of knee OA in African Americans. METHODS: We performed a genome-wide association study of radiographic knee OA in 1217 African Americans from 2 North American cohort studies: 590 subjects from the Johnston County Osteoarthritis Project and 627 subjects from the Osteoarthritis Initiative. Analyses were conducted in each cohort separately and combined in an inverse variance fixed effects metaanalysis, which were then included in pathway analyses. We additionally tested 12 single-nucleotide polymorphisms robustly associated with OA in European white populations for association in African Americans. RESULTS: We identified a genome-wide significant variant in LINC01006 (minor allele frequency 12%; p = 4.11 × 10-9) that is less common in European white populations (minor allele frequency < 3%). Five other independent loci reached suggestive significance (p < 1 × 10-6). In pathway analyses, dorsal/ventral neural tube patterning and iron ion transport pathways were significantly associated with knee OA in African Americans (false discovery rate < 0.05). We found no evidence that previously reported OA susceptibility variants in European whites were associated with knee OA in African Americans. CONCLUSION: These results highlight differences in the genetic architecture of knee OA between African American and European whites. This finding underscores the need to include more diverse populations in OA genetics studies.
OBJECTIVE: The etiology of knee osteoarthritis (OA), the most common form of arthritis, is complex and may differ by race or ethnicity. In recent years, genetic studies have identified many genetic variants associated with OA, but nearly all the studies were conducted in European whites and Asian Americans. Few studies have focused on the genetics of knee OA in African Americans. METHODS: We performed a genome-wide association study of radiographic knee OA in 1217 African Americans from 2 North American cohort studies: 590 subjects from the Johnston County Osteoarthritis Project and 627 subjects from the Osteoarthritis Initiative. Analyses were conducted in each cohort separately and combined in an inverse variance fixed effects metaanalysis, which were then included in pathway analyses. We additionally tested 12 single-nucleotide polymorphisms robustly associated with OA in European white populations for association in African Americans. RESULTS: We identified a genome-wide significant variant in LINC01006 (minor allele frequency 12%; p = 4.11 × 10-9) that is less common in European white populations (minor allele frequency < 3%). Five other independent loci reached suggestive significance (p < 1 × 10-6). In pathway analyses, dorsal/ventral neural tube patterning and iron ion transport pathways were significantly associated with knee OA in African Americans (false discovery rate < 0.05). We found no evidence that previously reported OA susceptibility variants in European whites were associated with knee OA in African Americans. CONCLUSION: These results highlight differences in the genetic architecture of knee OA between African American and European whites. This finding underscores the need to include more diverse populations in OA genetics studies.
Entities:
Keywords:
ETHNICITY; GENETICS; GENOME-WIDE ASSOCIATION STUDY; KNEE OSTEOARTHRITIS
Authors: Michelle S Yau; Laura M Yerges-Armstrong; Youfang Liu; Cora E Lewis; David J Duggan; Jordan B Renner; James Torner; David T Felson; Charles E McCulloch; C Kent Kwoh; Michael C Nevitt; Marc C Hochberg; Braxton D Mitchell; Joanne M Jordan; Rebecca D Jackson Journal: Arthritis Rheumatol Date: 2017-02 Impact factor: 10.995
Authors: P Heutink; J Zguricas; L van Oosterhout; G J Breedveld; L Testers; L A Sandkuijl; P J Snijders; J Weissenbach; D Lindhout; S E Hovius Journal: Nat Genet Date: 1994-03 Impact factor: 38.330
Authors: J Kettunen; M Perola; N G Martin; B K Cornes; S G Wilson; G W Montgomery; B Benyamin; J R Harris; D Boomsma; G Willemsen; J-J Hottenga; P E Slagboom; K Christensen; K O Kyvik; T I A Sørensen; N L Pedersen; P K E Magnusson; T Andrew; T D Spector; E Widen; K Silventoinen; J Kaprio; A Palotie; L Peltonen Journal: Int J Obes (Lond) Date: 2009-09-01 Impact factor: 5.095
Authors: Evangelos Evangelou; Ana M Valdes; Martha C Castano-Betancourt; M Doherty; Sally Doherty; Tonu Esko; Thorvaldur Ingvarsson; John P A Ioannidis; Margreet Kloppenburg; Andres Metspalu; Evangelia E Ntzani; Kalliope Panoutsopoulou; P Eline Slagboom; Lorraine Southam; Tim D Spector; Unnur Styrkarsdottir; Kari Stefanson; André G Uitterlinden; Margaret Wheeler; Eleftheria Zeggini; Ingrid Meulenbelt; Joyce B van Meurs Journal: Ann Rheum Dis Date: 2013-03-16 Impact factor: 19.103
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Authors: Daniel Richard; Zun Liu; Jiaxue Cao; Ata M Kiapour; Jessica Willen; Siddharth Yarlagadda; Evelyn Jagoda; Vijaya B Kolachalama; Jakob T Sieker; Gary H Chang; Pushpanathan Muthuirulan; Mariel Young; Anand Masson; Johannes Konrad; Shayan Hosseinzadeh; David E Maridas; Vicki Rosen; Roman Krawetz; Neil Roach; Terence D Capellini Journal: Cell Date: 2020-03-26 Impact factor: 41.582