9 results on '"Boer, C.G. (Cindy)"'
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2. Diversity, compositional and functional differences between gut microbiota of children and adults
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Radjabzadeh, D. (Djawad), Boer, C.G. (Cindy), Beth, S.A. (Sanne A.), van der Wal, P. (Pelle), Kiefte-de Jong, J.C. (Jessica), Jansen, M.A.E. (Michelle), Konstantinov, S.R. (Sergey), Peppelenbosch, M.P. (Maikel), Hays, J.P. (John P.), Jaddoe, V.W.V. (Vincent), Ikram, M.A. (Arfan), Rivadeneira, F. (Fernando), van Meurs, J.B.J. (Joyce B. J.), Uitterlinden, A.G. (André G.), Medina-Gomez, M.C. (Carolina), Moll, H.A. (Henriëtte), Kraaij, R. (Robert), Radjabzadeh, D. (Djawad), Boer, C.G. (Cindy), Beth, S.A. (Sanne A.), van der Wal, P. (Pelle), Kiefte-de Jong, J.C. (Jessica), Jansen, M.A.E. (Michelle), Konstantinov, S.R. (Sergey), Peppelenbosch, M.P. (Maikel), Hays, J.P. (John P.), Jaddoe, V.W.V. (Vincent), Ikram, M.A. (Arfan), Rivadeneira, F. (Fernando), van Meurs, J.B.J. (Joyce B. J.), Uitterlinden, A.G. (André G.), Medina-Gomez, M.C. (Carolina), Moll, H.A. (Henriëtte), and Kraaij, R. (Robert)
- Abstract
The gut microbiota has been shown to play diverse roles in human health and disease although the underlying mechanisms have not yet been fully elucidated. Large cohort studies can provide further understanding into inter-individual differences, with more precise characterization of the pathways by which the gut microbiota influences human physiology and disease processes. Here, we aimed to profile the stool microbiome of children and adults from two population-based cohort studies, comprising 2,111 children in the age-range of 9 to 12 years (the Generation R Study) and 1,427 adult individuals in the range of 46 to 88 years of age (the Rotterdam Study). For the two cohorts, 16S rRNA gene profile datasets derived from the Dutch population were generated. The comparison of the two cohorts showed that children had significantly lower gut microbiome diversity. Furthermore, we observed higher relative abundances of genus Bacteroides in children and higher relative abundances of genus Blautia in adults. Predicted functional metagenome analysis showed an overrepresentation of the glycan degradation pathways, riboflavin (vitamin B2), pyridoxine (vitamin B6) and folate (vitamin B9) biosynthesis pathways in children. In contrast, the gut microbiome of adults showed higher abundances of carbohydrate metabolism pathways, beta-lactam resistance, thiamine (vitamin B1) and pantothenic (vitamin B5) biosynthesis pathways. A predominance of catabolic pathways in children (valine, leucine and isoleucine degradation) as compared to biosynthetic pathways in adults (valine, leucine and isoleucine biosynthesis) suggests a functional microbiome switch to the latter in adult individuals. Overall, we identified compositional and functional differences in gut microbiome between children and adults in a population-based setting. These microbiome profiles can serve as reference for future studies on specific human disease susceptibility in childhood, adulthood and specific diseased populations.
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- 2020
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3. Intestinal microbiome composition and its relation to joint pain and inflammation
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Boer, C.G. (Cindy), Radjabzadeh, D. (Djawad), Medina-Gomez, M.C. (Carolina), Garmaeva, S. (Sanzhima), Schiphof, D. (Dieuwke), Arp, P.P. (Pascal), Koet, T. (Thomas), Kurilshikov, A. (Alexander), Fu, J. (Jingyuan), Ikram, M.A. (Arfan), Bierma-Zeinstra, S.M. (Sita), Uitterlinden, A.G. (André), Kraaij, R. (Robert), Zhernakova, A. (Alexandra), Meurs, J.B.J. (Joyce) van, Boer, C.G. (Cindy), Radjabzadeh, D. (Djawad), Medina-Gomez, M.C. (Carolina), Garmaeva, S. (Sanzhima), Schiphof, D. (Dieuwke), Arp, P.P. (Pascal), Koet, T. (Thomas), Kurilshikov, A. (Alexander), Fu, J. (Jingyuan), Ikram, M.A. (Arfan), Bierma-Zeinstra, S.M. (Sita), Uitterlinden, A.G. (André), Kraaij, R. (Robert), Zhernakova, A. (Alexandra), and Meurs, J.B.J. (Joyce) van
- Abstract
Macrophage-mediated inflammation is thought to have a causal role in osteoarthritis-related pain and severity, and has been suggested to be triggered by endotoxins produced by the gastrointestinal microbiome. Here we investigate the relationship between joint pain and the gastrointestinal microbiome composition, and osteoarthritis-related knee pain in the Rotterdam Study; a large population based cohort study. We show that abundance of Streptococcus species is associated with increased knee pain, which we validate by absolute quantification of Streptococcus species. In addition, we replicate these results in 867 Caucasian adults of the Lifelines-DEEP study. Finally we show evidence that this association is driven by local inflammation in the knee joint. Our results indicate the microbiome is a possible therapeutic target for osteoarthritis-related knee pain.
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- 2019
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4. Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain
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Suri, P. (Pradeep), Palmer, M.R. (Melody R.), Tsepilov, Y.A. (Yakov), Freidin, M.B. (Maxim B.), Boer, C.G. (Cindy), Yau, M.S. (Michelle S.), Evans, D.S. (Daniel), Gelemanovic, A. (Andrea), Bartz, T.M. (Traci M.), Nethander, M. (Maria), Arbeeva, L. (Liubov), Karssen, L.C. (Lennart), Neogi, T. (Tuhina), Campbell, A. (Archie), Mellström, D. (Dan), Ohlsson, C. (Claes), Marshall, L.M. (Lynn M.), Orwoll, E. (Eric), Uitterlinden, A. (Andre), Rotter, J.I. (Jerome I.), Lauc, G. (Gordan), Psaty, B.M. (Bruce M.), Karlsson, M. (Magnus), Lane, N.E., Jarvik, G.P. (Gail), Polasek, O. (Ozren), Hochberg, M.C. (Marc), Jordan, J.M. (Joanne), Meurs, J.B.J. (Joyce) van, Jackson, R.D. (Rebecca), Nielson, C. (Carrie), Mitchell, B.D. (Braxton), Smith, B.H. (Blair), Hayward, C. (Caroline), Smith, N.L. (Nicholas L.), Aulchenko, Y.S. (Yurii S.), Williams, F.M. (Frances), Suri, P. (Pradeep), Palmer, M.R. (Melody R.), Tsepilov, Y.A. (Yakov), Freidin, M.B. (Maxim B.), Boer, C.G. (Cindy), Yau, M.S. (Michelle S.), Evans, D.S. (Daniel), Gelemanovic, A. (Andrea), Bartz, T.M. (Traci M.), Nethander, M. (Maria), Arbeeva, L. (Liubov), Karssen, L.C. (Lennart), Neogi, T. (Tuhina), Campbell, A. (Archie), Mellström, D. (Dan), Ohlsson, C. (Claes), Marshall, L.M. (Lynn M.), Orwoll, E. (Eric), Uitterlinden, A. (Andre), Rotter, J.I. (Jerome I.), Lauc, G. (Gordan), Psaty, B.M. (Bruce M.), Karlsson, M. (Magnus), Lane, N.E., Jarvik, G.P. (Gail), Polasek, O. (Ozren), Hochberg, M.C. (Marc), Jordan, J.M. (Joanne), Meurs, J.B.J. (Joyce) van, Jackson, R.D. (Rebecca), Nielson, C. (Carrie), Mitchell, B.D. (Braxton), Smith, B.H. (Blair), Hayward, C. (Caroline), Smith, N.L. (Nicholas L.), Aulchenko, Y.S. (Yurii S.), and Williams, F.M. (Frances)
- Abstract
Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chr
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- 2018
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5. A DNA methylation biomarker of alcohol consumption
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Liu, C. (C.), Marioni, R.E. (Riccardo), Hedman, A.K. (Asa), Pfeiffer, L. (L.), Tsai, P.-C. (P. C.), Reynolds, L.M. (Lindsay), Just, A.C. (A. C.), Duan, Q. (Qing), Boer, C.G. (Cindy), Tanaka, T. (T.), Elks, C.E. (Cathy), Aslibekyan, S. (S.), Brody, J.A. (Jennifer A.), Kuhnel, B. (Brigitte), Herder, C. (Christian), Almli, L.M. (L. M.), Zhi, D. (D.), Wang, Y. (Y.), Huan, T. (T.), Yao, C. (C.), Mendelson, M.M. (M. M.), Joehanes, R. (Roby), Liang, L. (Liming), Love, S.-A. (S. A.), Guan, W. (Weihua), Shah, S. (S.), McRae, A.F. (A. F.), Kretschmer, A. (A.), Prokisch, H. (Holger), Strauch, K. (K.), Peters, A. (Annette), Visscher, P.M. (Peter), Wray, N.R. (Naomi), Guo, X. (Xiuqing), Wiggins, K.L. (Kerri), Smith, A.K. (A. K.), Binder, E.B. (Elisabeth), Ressler, K.J. (Kerry), Irvin, M.R. (M. R.), Absher, D.M. (D. M.), Hernandez, D.G. (Dena), Ferrucci, L. (Luigi), Bandinelli, S. (Stefania), Lohman, K. (K.), Ding, J. (J.), Trevisi, L. (L.), Gustafsson, S. (Stefan), Sandling, J.K. (Johanna), Stolk, L. (Lisette), Uitterlinden, A.G. (André), Yet, I. (Idil), Castillo-Fernandez, J.E. (J. E.), Spector, T.D. (Timothy), Schwartz, J.D. (J. D.), Vokonas, P. (P.), Kao, W.H.L. (Wen), Li, Y. (Y.), Fornage, M. (Myriam), Arnett, D.K. (Donna), Wareham, N.J. (Nick), Sotoodehnia, N. (Nona), Ong, K.K. (Ken), Meurs, J.B.J. (Joyce) van, Conneely, K.N. (Karen N.), Baccarelli, A.A. (A. A.), Deary, I.J. (Ian), Bell, J.T. (J. T.), North, K.E. (Kari), Liu, Y. (YongMei), Waldenberger, M. (M.), London, S.J. (S. J.), Ingelsson, E. (Erik), Levy, D. (D.), Liu, C. (C.), Marioni, R.E. (Riccardo), Hedman, A.K. (Asa), Pfeiffer, L. (L.), Tsai, P.-C. (P. C.), Reynolds, L.M. (Lindsay), Just, A.C. (A. C.), Duan, Q. (Qing), Boer, C.G. (Cindy), Tanaka, T. (T.), Elks, C.E. (Cathy), Aslibekyan, S. (S.), Brody, J.A. (Jennifer A.), Kuhnel, B. (Brigitte), Herder, C. (Christian), Almli, L.M. (L. M.), Zhi, D. (D.), Wang, Y. (Y.), Huan, T. (T.), Yao, C. (C.), Mendelson, M.M. (M. M.), Joehanes, R. (Roby), Liang, L. (Liming), Love, S.-A. (S. A.), Guan, W. (Weihua), Shah, S. (S.), McRae, A.F. (A. F.), Kretschmer, A. (A.), Prokisch, H. (Holger), Strauch, K. (K.), Peters, A. (Annette), Visscher, P.M. (Peter), Wray, N.R. (Naomi), Guo, X. (Xiuqing), Wiggins, K.L. (Kerri), Smith, A.K. (A. K.), Binder, E.B. (Elisabeth), Ressler, K.J. (Kerry), Irvin, M.R. (M. R.), Absher, D.M. (D. M.), Hernandez, D.G. (Dena), Ferrucci, L. (Luigi), Bandinelli, S. (Stefania), Lohman, K. (K.), Ding, J. (J.), Trevisi, L. (L.), Gustafsson, S. (Stefan), Sandling, J.K. (Johanna), Stolk, L. (Lisette), Uitterlinden, A.G. (André), Yet, I. (Idil), Castillo-Fernandez, J.E. (J. E.), Spector, T.D. (Timothy), Schwartz, J.D. (J. D.), Vokonas, P. (P.), Kao, W.H.L. (Wen), Li, Y. (Y.), Fornage, M. (Myriam), Arnett, D.K. (Donna), Wareham, N.J. (Nick), Sotoodehnia, N. (Nona), Ong, K.K. (Ken), Meurs, J.B.J. (Joyce) van, Conneely, K.N. (Karen N.), Baccarelli, A.A. (A. A.), Deary, I.J. (Ian), Bell, J.T. (J. T.), North, K.E. (Kari), Liu, Y. (YongMei), Waldenberger, M. (M.), London, S.J. (S. J.), Ingelsson, E. (Erik), and Levy, D. (D.)
- Abstract
The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal = 13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n = 6926) and identified 144 CpGs that provided substantial discrimination (area under the curve = 0.90-0.99) for current heavy alcohol intake (≥42 g per day in men and ≥28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1×10-7. Analysis of the monocyte-derived DNA (n = 1251) identified 62 alcohol-related CpGs at P<1×10-7. In whole-blood samples of people of European ancestry, we detected differen
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- 2018
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6. Genome-wide association study identifies nine novel loci for 2D:4D finger ratio, a putative retrospective biomarker of testosterone exposure in utero
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Warrington, N.M. (Nicole M.), Shevroja, E. (Enisa), Hemani, G., Hysi, P.G. (Pirro), Jiang, Y. (Yunxuan), Auton, A. (Adam), Boer, C.G. (Cindy), Mangino, M. (Massimo), Wang, C.A. (Carol A.), Kemp, J.P. (John), Mcmahon, G. (George), Medina-Gomez, M.C. (Carolina), Hickey, M. (Martha), Trajanoska, K. (Katerina), Wolke, D. (Dieter), Ikram, M.A. (Arfan), Montgomery, G.W. (Grant W.), Felix, J.F. (Janine F.), Wright, M.J. (Margaret J.), Mackey, D.A. (David), Jaddoe, V.W.V. (Vincent), Martin, N.G. (Nicholas), Tung, J.Y. (Joyce Y.), Smith, G.D. (George Davey), Pennell, C.E. (Craig), Spector, T.D. (Timothy), Meurs, J.B.J. (Joyce) van, Rivadeneira, F. (Fernando), Medland, S.E. (Sarah), Evans, D.M. (David M.), The 23and Me Research Team, (), Warrington, N.M. (Nicole M.), Shevroja, E. (Enisa), Hemani, G., Hysi, P.G. (Pirro), Jiang, Y. (Yunxuan), Auton, A. (Adam), Boer, C.G. (Cindy), Mangino, M. (Massimo), Wang, C.A. (Carol A.), Kemp, J.P. (John), Mcmahon, G. (George), Medina-Gomez, M.C. (Carolina), Hickey, M. (Martha), Trajanoska, K. (Katerina), Wolke, D. (Dieter), Ikram, M.A. (Arfan), Montgomery, G.W. (Grant W.), Felix, J.F. (Janine F.), Wright, M.J. (Margaret J.), Mackey, D.A. (David), Jaddoe, V.W.V. (Vincent), Martin, N.G. (Nicholas), Tung, J.Y. (Joyce Y.), Smith, G.D. (George Davey), Pennell, C.E. (Craig), Spector, T.D. (Timothy), Meurs, J.B.J. (Joyce) van, Rivadeneira, F. (Fernando), Medland, S.E. (Sarah), Evans, D.M. (David M.), and The 23and Me Research Team, ()
- Abstract
The ratio of the length of the index finger to that of the ring finger (2D:4D) is sexually dimorphic and is commonly used as a non-invasive biomarker of prenatal androgen exposure. Most association studies of 2D:4D ratio with a diverse range of sexspecific traits have typically involved small sample sizes and have been difficult to replicate, raising questions around the utility and precise meaning of the measure. In the largest genome-wide association meta-analysis of 2D:4D ratio to date (N=15 661, with replication N=75 821), we identified 11 loci (9 novel) explaining 3.8% of the variance in mean 2D:4D ratio. We also found weak evidence for association (b=0.06; P=0.02) between 2D:4D ratio and sensitivity to testosterone [length of the CAG microsatellite repeat in the androgen receptor (AR) gene] in females only. Furthermore, genetic variants associated with (adult) testosterone levels and/or sex hormone-binding globulin were not associated with 2D:4D ratio in our sample. Although we were unable to find strong evidence from our genetic study to support the hypothesis that 2D:4D ratio is a direct biomarker of prenatal exposure to androgens in healthy individuals, our findings do not explicitly exclude this possibility, and pathways involving testosterone may become apparent as the size of the discovery sample increases further. Our findings provide new insight into the underlying biology shaping 2D:4D variation in the general population.
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- 2018
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7. Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand
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Hollander, W. (Wouter) den, Boer, C.G. (Cindy G.), Hart, D.J. (Deborah), Yau, M.S. (Michelle S.), Ramos, Y.F.M. (Yolande F.M.), Metrustry, S. (Sarah), Broer, L. (Linda), Deelen, J. (Joris), Cupples, L.A. (Adrienne), Rivadeneira, F. (Fernando), Kloppenburg, M. (Margreet), Peters, M.A.D. (Marjolein), Spector, T.D. (Timothy), Hofman, A. (Albert), Slagboom, P.E. (Eline), Nelissen, R.G.H.H. (Rob), Uitterlinden, A.G. (André), Felson, D., Valdes, A.M. (Ana Maria), Meulenbelt, I. (Ingrid), Van Meurs, J.J.B. (Joyce J. B.), Hollander, W. (Wouter) den, Boer, C.G. (Cindy G.), Hart, D.J. (Deborah), Yau, M.S. (Michelle S.), Ramos, Y.F.M. (Yolande F.M.), Metrustry, S. (Sarah), Broer, L. (Linda), Deelen, J. (Joris), Cupples, L.A. (Adrienne), Rivadeneira, F. (Fernando), Kloppenburg, M. (Margreet), Peters, M.A.D. (Marjolein), Spector, T.D. (Timothy), Hofman, A. (Albert), Slagboom, P.E. (Eline), Nelissen, R.G.H.H. (Rob), Uitterlinden, A.G. (André), Felson, D., Valdes, A.M. (Ana Maria), Meulenbelt, I. (Ingrid), and Van Meurs, J.J.B. (Joyce J. B.)
- Abstract
Objective Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the elderly. Of all the joints, genetic predisposition is strongest for OA of the hand; however, only few genetic risk loci for hand OA have been identified. Our aim was to identify novel genes associated with hand OA and examine the underlying mechanism. Methods We performed a genome-wide association study of a quantitative measure of hand OA in 12 784 individuals (discovery: 8743, replication: 4011). Genome-wide significant signals were followed up by analysing gene and allele-specific expression in a RNA sequencing dataset (n=96) of human articular cartilage. Results We found two significantly associated loci in the discovery set: at chr12 (p=3.5 × 10 -10) near the matrix Gla protein (MGP) gene and at chr12 (p=6.1×10 -9) near the CCDC91 gene. The DNA variant near t
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- 2017
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8. Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
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Medina-Gomez, M.C. (Carolina), Kemp, J.P. (John), Dimou, N.L. (Niki L.), Kreiner, E. (Eskil), Chesi, A. (Alessandra), Zemel, B.S. (Babette S.), Bønnelykke, K. (Klaus), Boer, C.G. (Cindy G.), Ahluwalia, T.S. (Tarunveer Singh), Bisgaard, H. (Hans), Evangelou, E. (Evangelos), Heppe, D.H.M. (Denise), Bonewald, L.F. (Lynda F.), Gorski, J.P. (Jeffrey P.), Ghanbari, M. (Mohsen), Demissie, S. (Serkalem), Duque, G. (Gustavo), Maurano, M.T. (Matthew T.), Kiel, D.P. (Douglas P.), Hsu, Y.-H. (Yi-Hsiang), Eerden, B.C.J. (Bram) van der, Ackert-Bicknell, C. (Cheryl), Reppe, S. (Sjur), Gautvik, K.M. (Kaare), Raastad, T. (Truls), Karasik, D. (David), Peppel, J. (Jeroen) van de, Jaddoe, V.W.V. (Vincent), Uitterlinden, A.G. (André), Tobias, J.H. (Jon), Grant, S.F.A. (Struan), Bagos, P.G. (Pantelis G.), Evans, D.M. (David), Rivadeneira Ramirez, F. (Fernando), Medina-Gomez, M.C. (Carolina), Kemp, J.P. (John), Dimou, N.L. (Niki L.), Kreiner, E. (Eskil), Chesi, A. (Alessandra), Zemel, B.S. (Babette S.), Bønnelykke, K. (Klaus), Boer, C.G. (Cindy G.), Ahluwalia, T.S. (Tarunveer Singh), Bisgaard, H. (Hans), Evangelou, E. (Evangelos), Heppe, D.H.M. (Denise), Bonewald, L.F. (Lynda F.), Gorski, J.P. (Jeffrey P.), Ghanbari, M. (Mohsen), Demissie, S. (Serkalem), Duque, G. (Gustavo), Maurano, M.T. (Matthew T.), Kiel, D.P. (Douglas P.), Hsu, Y.-H. (Yi-Hsiang), Eerden, B.C.J. (Bram) van der, Ackert-Bicknell, C. (Cheryl), Reppe, S. (Sjur), Gautvik, K.M. (Kaare), Raastad, T. (Truls), Karasik, D. (David), Peppel, J. (Jeroen) van de, Jaddoe, V.W.V. (Vincent), Uitterlinden, A.G. (André), Tobias, J.H. (Jon), Grant, S.F.A. (Struan), Bagos, P.G. (Pantelis G.), Evans, D.M. (David), and Rivadeneira Ramirez, F. (Fernando)
- Abstract
Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% for TBLH-BMD, and 39% for TB-LM, with a shared genetic component of 43%. We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: _WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5_. Variants in the _TOM1L2/SREBF1_ locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that _SREBF1_ is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.
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- 2017
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9. Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis
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Castaño Betancourt, M.C. (Martha), Evans, D.S. (Daniel), Ramos, Y.F.M. (Yolande), Boer, C.G. (Cindy G.), Metrustry, S. (Sarah), Liu, Y. (Youfang), Hollander, W. (Wouter) den, Rooij, J.G.J. (Jeroen) van, Kraus, V.B. (Virginia B.), Yau, M.S. (Michelle S.), Mitchell, B.D. (Braxton), Muir, K. (Kenneth), Hofman, A. (Albert), Doherty, M. (Michael), Doherty, S. (Sally), Zhang, W. (Weiya), Kraaij, R. (Robert), Rivadeneira Ramirez, F. (Fernando), Barrett-Connor, E. (Elizabeth), MacIewicz, R.A. (Rose), Arden, N.K. (Nigel), Nelissen, R.G.H.H. (Rob), Kloppenburg, M. (Margreet), Jordan, J.M. (Joanne M.), Nevitt, M.C. (Michael), Slagboom, P.E. (Eline), Hart, D. (Deborah), Lafeber, F.P.J.G. (Floris), Styrkarsdottir, U. (Unnur), Zeggini, E. (Eleftheria), Evangelou, E. (Evangelos), Spector, T.D. (Timothy), Uitterlinden, A.G. (André), Lane, N.E., Meulenbelt, I. (Ingrid), Valdes, A.M. (Ana Maria), Meurs, J.B.J. (Joyce) van, Castaño Betancourt, M.C. (Martha), Evans, D.S. (Daniel), Ramos, Y.F.M. (Yolande), Boer, C.G. (Cindy G.), Metrustry, S. (Sarah), Liu, Y. (Youfang), Hollander, W. (Wouter) den, Rooij, J.G.J. (Jeroen) van, Kraus, V.B. (Virginia B.), Yau, M.S. (Michelle S.), Mitchell, B.D. (Braxton), Muir, K. (Kenneth), Hofman, A. (Albert), Doherty, M. (Michael), Doherty, S. (Sally), Zhang, W. (Weiya), Kraaij, R. (Robert), Rivadeneira Ramirez, F. (Fernando), Barrett-Connor, E. (Elizabeth), MacIewicz, R.A. (Rose), Arden, N.K. (Nigel), Nelissen, R.G.H.H. (Rob), Kloppenburg, M. (Margreet), Jordan, J.M. (Joanne M.), Nevitt, M.C. (Michael), Slagboom, P.E. (Eline), Hart, D. (Deborah), Lafeber, F.P.J.G. (Floris), Styrkarsdottir, U. (Unnur), Zeggini, E. (Eleftheria), Evangelou, E. (Evangelos), Spector, T.D. (Timothy), Uitterlinden, A.G. (André), Lane, N.E., Meulenbelt, I. (Ingrid), Valdes, A.M. (Ana Maria), and Meurs, J.B.J. (Joyce) van
- Abstract
Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547
- Published
- 2016
- Full Text
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