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4. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Author

Boer, Cindy G., primary, Hatzikotoulas, Konstantinos, additional, Southam, Lorraine, additional, Stefánsdóttir, Lilja, additional, Zhang, Yanfei, additional, Coutinho de Almeida, Rodrigo, additional, Wu, Tian T., additional, Zheng, Jie, additional, Hartley, April, additional, Teder-Laving, Maris, additional, Skogholt, Anne Heidi, additional, Terao, Chikashi, additional, Zengini, Eleni, additional, Alexiadis, George, additional, Barysenka, Andrei, additional, Bjornsdottir, Gyda, additional, Gabrielsen, Maiken E., additional, Gilly, Arthur, additional, Ingvarsson, Thorvaldur, additional, Johnsen, Marianne B., additional, Jonsson, Helgi, additional, Kloppenburg, Margreet, additional, Luetge, Almut, additional, Lund, Sigrun H., additional, Mägi, Reedik, additional, Mangino, Massimo, additional, Nelissen, Rob R.G.H.H., additional, Shivakumar, Manu, additional, Steinberg, Julia, additional, Takuwa, Hiroshi, additional, Thomas, Laurent F., additional, Tuerlings, Margo, additional, Babis, George C., additional, Cheung, Jason Pui Yin, additional, Kang, Jae Hee, additional, Kraft, Peter, additional, Lietman, Steven A., additional, Samartzis, Dino, additional, Slagboom, P. Eline, additional, Stefansson, Kari, additional, Thorsteinsdottir, Unnur, additional, Tobias, Jonathan H., additional, Uitterlinden, André G., additional, Winsvold, Bendik, additional, Zwart, John-Anker, additional, Davey Smith, George, additional, Sham, Pak Chung, additional, Thorleifsson, Gudmar, additional, Gaunt, Tom R., additional, Morris, Andrew P., additional, Valdes, Ana M., additional, Tsezou, Aspasia, additional, Cheah, Kathryn S.E., additional, Ikegawa, Shiro, additional, Hveem, Kristian, additional, Esko, Tõnu, additional, Wilkinson, J. Mark, additional, Meulenbelt, Ingrid, additional, Lee, Ming Ta Michael, additional, van Meurs, Joyce B.J., additional, Styrkársdóttir, Unnur, additional, Zeggini, Eleftheria, additional, Loughlin, John, additional, Arden, Nigel, additional, Birrell, Fraser, additional, Carr, Andrew, additional, Deloukas, Panos, additional, Doherty, Michael, additional, McCaskie, Andrew W., additional, Ollier, William E.R., additional, Rai, Ashok, additional, Ralston, Stuart H., additional, Spector, Tim D., additional, Wallis, Gillian A., additional, Martinsen, Amy E., additional, Willer, Cristen, additional, Fors, Egil Andreas, additional, Mundal, Ingunn, additional, Hagen, Knut, additional, Nilsen, Kristian Bernhard, additional, Lie, Marie Udnesseter, additional, Børte, Sigrid, additional, Brumpton, Ben, additional, Nielsen, Jonas Bille, additional, Fritsche, Lars G., additional, Zhou, Wei, additional, Heuch, Ingrid, additional, Storheim, Kjersti, additional, Tyrpenou, Evangelos, additional, Koukakis, Athanasios, additional, Chytas, Dimitrios, additional, Evangelopoulos, Dimitrios Stergios, additional, Efstathios, Chronopoulos, additional, Pneumaticos, Spiros, additional, Nikolaou, Vasileios S., additional, Malizos, Konstantinos, additional, Anastasopoulou, Lydia, additional, Abecasis, Goncalo, additional, Baras, Aris, additional, Cantor, Michael, additional, Coppola, Giovanni, additional, Deubler, Andrew, additional, Economides, Aris, additional, Lotta, Luca A., additional, Overton, John D., additional, Reid, Jeffrey G., additional, Shuldiner, Alan, additional, Karalis, Katia, additional, Siminovitch, Katherine, additional, Beechert, Christina, additional, Forsythe, Caitlin, additional, Fuller, Erin D., additional, Gu, Zhenhua, additional, Lattari, Michael, additional, Lopez, Alexander, additional, Schleicher, Thomas D., additional, Padilla, Maria Sotiropoulos, additional, Widom, Louis, additional, Wolf, Sarah E., additional, Pradhan, Manasi, additional, Manoochehri, Kia, additional, Bai, Xiaodong, additional, Balasubramanian, Suganthi, additional, Boutkov, Boris, additional, Eom, Gisu, additional, Habegger, Lukas, additional, Hawes, Alicia, additional, Krasheninina, Olga, additional, Lanche, Rouel, additional, Mansfield, Adam J., additional, Maxwell, Evan K., additional, Nafde, Mona, additional, O’Keeffe, Sean, additional, Orelus, Max, additional, Panea, Razvan, additional, Polanco, Tommy, additional, Rasool, Ayesha, additional, Salerno, William, additional, Staples, Jeffrey C., additional, Li, Dadong, additional, Sharma, Deepika, additional, Banerjee, Ilanjana, additional, Bovijn, Jonas, additional, Locke, Adam, additional, Verweij, Niek, additional, Haas, Mary, additional, Hindy, George, additional, De, Tanima, additional, Akbari, Parsa, additional, Sosina, Olukayode, additional, Ferreira, Manuel A.R., additional, Jones, Marcus B., additional, Mighty, Jason, additional, LeBlanc, Michelle G., additional, and Mitnaul, Lyndon J., additional

Published
2021
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7. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Author

Boer, Cindy G., Hatzikotoulas, Konstantinos, Southam, Lorraine, Stefánsdóttir, Lilja, Zhang, Yanfei, Coutinho de Almeida, Rodrigo, Wu, Tian T., Zheng, Jie, Hartley, April, Teder-Laving, Maris, Skogholt, Anne Heidi, Terao, Chikashi, Zengini, Eleni, Alexiadis, George, Barysenka, Andrei, Bjornsdottir, Gyda, Gabrielsen, Maiken E., Gilly, Arthur, Ingvarsson, Thorvaldur, Johnsen, Marianne B., Jonsson, Helgi, Kloppenburg, Margreet, Luetge, Almut, Lund, Sigrun H., Mägi, Reedik, Mangino, Massimo, Nelissen, Rob R.G.H.H., Shivakumar, Manu, Steinberg, Julia, Takuwa, Hiroshi, Thomas, Laurent F., Tuerlings, Margo, Loughlin, John, Arden, Nigel, Birrell, Fraser, Carr, Andrew, Deloukas, Panos, Doherty, Michael, McCaskie, Andrew W., Ollier, William E.R., Rai, Ashok, Ralston, Stuart H., Spector, Tim D., Wallis, Gillian A., Martinsen, Amy E., Willer, Cristen, Verweij, Niek, Kraft, Peter, Uitterlinden, André G., van Meurs, Joyce B.J., Styrkarsdottir, U, Zeggini, E, Boer, Cindy G., Hatzikotoulas, Konstantinos, Southam, Lorraine, Stefánsdóttir, Lilja, Zhang, Yanfei, Coutinho de Almeida, Rodrigo, Wu, Tian T., Zheng, Jie, Hartley, April, Teder-Laving, Maris, Skogholt, Anne Heidi, Terao, Chikashi, Zengini, Eleni, Alexiadis, George, Barysenka, Andrei, Bjornsdottir, Gyda, Gabrielsen, Maiken E., Gilly, Arthur, Ingvarsson, Thorvaldur, Johnsen, Marianne B., Jonsson, Helgi, Kloppenburg, Margreet, Luetge, Almut, Lund, Sigrun H., Mägi, Reedik, Mangino, Massimo, Nelissen, Rob R.G.H.H., Shivakumar, Manu, Steinberg, Julia, Takuwa, Hiroshi, Thomas, Laurent F., Tuerlings, Margo, Loughlin, John, Arden, Nigel, Birrell, Fraser, Carr, Andrew, Deloukas, Panos, Doherty, Michael, McCaskie, Andrew W., Ollier, William E.R., Rai, Ashok, Ralston, Stuart H., Spector, Tim D., Wallis, Gillian A., Martinsen, Amy E., Willer, Cristen, Verweij, Niek, Kraft, Peter, Uitterlinden, André G., van Meurs, Joyce B.J., Styrkarsdottir, U, and Zeggini, E

Abstract

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

Published
2021

14. Interferon-gamma and interleukin-4 gene polymorphisms in Caucasian idiopathic inflammatory myopathy patients in UK

Author

Chinoy, Hector, Salway, Fiona, John, Sally, Fertig, Noreen, Tait, Brian D., Oddis, Chester V., Ollier, William E.R., and Cooper, Robert G.

Subjects
Muscle diseases -- Genetic aspects, Muscle diseases -- Research, Interferon gamma -- Genetic aspects, Interferon gamma -- Research, Interleukin-4 -- Genetic aspects, Interleukin-4 -- Research, Genetic polymorphisms -- Research, Health
Published
2007

22. Should patients with recent onset rheumatoid arthritis be offered genetic screening?

Author

Symmons, Deborah P.M., Ollier, William E.R., Brennan, Paul, and Silman, Alan J.

Subjects
Rheumatoid arthritis -- Genetic aspects, Genetic screening -- Planning, HLA class II antigens -- Health aspects, Health
Abstract

It does not appear appropriate to offer routine genetic screening for rheumatoid arthritis (RA) until more is known of the results' implications and the tests are more reliable. Researchers have found a strong association between RA and a section of chromosome six called the HLA complex that codes for immune responses and contains a sequence called the shared epitope. However, studies are inconclusive as to whether patients who test positive for this genetic complex will develop a worse form of this disease or would benefit from early treatment.

Published
1996

25. Analysis of candidate susceptibility genes in canine diabetes

Author

Short, Andrea D., Catchpole, Brian, Kennedy, Lorna J., Barnes, Annette, Fretwell, Neale, Jones, Chris, Thomson, Wendy, and Ollier, William E.R.

Subjects
Dogs -- Genetic aspects, Single nucleotide polymorphisms -- Analysis, Diabetes -- Analysis, Biological sciences
Abstract

The study results from a single-nucleotide polymorphism (SNP)-based analysis of canine diabetes mellitus (DM) in a diabetic cohort which identified 11, 10 haplotype associated with diabetes in the Cavalier King Charles Spaniel are reported.

Published
2007

26. DLA-DRB1, DQA1, and DQB1 alleles and haplotypes in North American gray wolves

Author

Kennedy, Lorna J., Angles, John M., Barnes, Annette, Carmichael, Lindsey E., Radford, Alan D., Ollier, William E.R., and Happ, George M.

Subjects
Allelomorphism -- Research, Histocompatibility -- Analysis, Wolves -- Genetic aspects, Dogs -- Genetic aspects, Biological sciences
Abstract

The determination of the nature and degree of polymorphism for major histocompatibility complex class II loci DLA-DRB1, DQA1, and DQB1 for the Alaskan and Canadian gray wolves in several geographically separated regions is presented. It indicates that the wolf ancestors of Asian and European dogs might had different gene pools, reflected in the DLA alleles present in dog breeds.

Published
2007

27. Hardy-Weinberg expectations in canine breeds: Implications for genetic studies

Author

Short, Andrea D., Kennedy, Lorna J., Barnes, Annette, Fretwell, Neale, Jones, Chris, Thomson, Wendy, and Ollier, William E.R.

Subjects
Dogs -- Genetic aspects, Hardy-Weinberg formula -- Analysis, Biological sciences
Abstract

Studies are conducted to examine whether breeds and subbreeds comply with Hardy-Weinberg equilibrium (HWE) as a useful indicator of genotype frequencies within a population. Results indicate that canine case-control association studies would be reasonable if performed within defined breeds.

Published
2007

28. Lack of influence of non-inherited maternal HLA-DR alleles on susceptibility to rheumatoid arthritis

Author

Silman, Alan J., Hay, Elaine M., Worthington, Jane, Thomson, Wendy, Pepper, Lynne, Davidson, Jude, Dyer, Phil A., and Ollier, William E.R.

Subjects
HLA class II antigens -- Physiological aspects, Disease susceptibility -- Research, Rheumatoid arthritis, Health
Abstract

Non-inherited maternal HLA-DR alleles may not increase susceptibility to rheumatoid arthritis (RA). The HLA-DR bands on human chromosomes have been associated in some studies to be related to maternal transfer as well as paternal transfer of a genetic risk factor for RA. In a study of families from a registry of RA patients, non-inherited maternal antigens (NIMA) from DR genes and non-inherited paternal antigens (NIPA) from DR genes were compared on DNA from 74 rheumatoid factor positive individuals from 39 families with more than one member with RA and their first-degree relatives. There was no increase in frequency of NIMA DR varieties of genes when compared with NIPA DR gene varieties. Since there are plausible arguments for these findings which do not exclude the hypotheses concerning both parents contribution to RA susceptibility, further research needs to be done.

Published
1995

30. Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies

Author

Rodríguez-Fontenla, Cristina, Calaza, Manuel, Evangelou, Evangelos, Valdés, Ana M., Arden, Nigel, Blanco García, Francisco J, Carr, Andrew, Chapman, Kay, Deloukas, Panos, Doherty, Michael, Esko, Tonu, Garcés Aletá, Carlos M., Gómez-Reino Carnota, Juan J., Helgadottir, Hafids, Hofman, Albert, Jonsdottir, Ingilef, Kerkhof, Henneke J.M., Kloppenburg, Margreet, McCaskie, Andrew, Ntzani, Evangelia E., Ollier, William E.R., Oreiro, Natividad, Panoutsopoulo, Kalliope, Ralston, Stuart H., Ramos, Yolande F. M., Riancho, José A., Rivadeneira, Fernando, Slagboom, Eline, Styrkarsdottir, Unnur, Thorsteindottir, Unnur, Thorleifsson, Gudmar, Tsezou, Aspasia, Uitterlinden, André G., Wallis, Gillian A., Wilkinson, J. Mark, Zhai, Yanyan, Felson, David T., Ioannidis, John P.A., Loughlin, John, Metspalu, Andres, Meulenbelt, Ingrid, Stefansson, Kari, van Meurs, Joyce B., Zeggini, Eleftheria, Spector, Timothy D., González, Antonio, Rodríguez-Fontenla, Cristina, Calaza, Manuel, Evangelou, Evangelos, Valdés, Ana M., Arden, Nigel, Blanco García, Francisco J, Carr, Andrew, Chapman, Kay, Deloukas, Panos, Doherty, Michael, Esko, Tonu, Garcés Aletá, Carlos M., Gómez-Reino Carnota, Juan J., Helgadottir, Hafids, Hofman, Albert, Jonsdottir, Ingilef, Kerkhof, Henneke J.M., Kloppenburg, Margreet, McCaskie, Andrew, Ntzani, Evangelia E., Ollier, William E.R., Oreiro, Natividad, Panoutsopoulo, Kalliope, Ralston, Stuart H., Ramos, Yolande F. M., Riancho, José A., Rivadeneira, Fernando, Slagboom, Eline, Styrkarsdottir, Unnur, Thorsteindottir, Unnur, Thorleifsson, Gudmar, Tsezou, Aspasia, Uitterlinden, André G., Wallis, Gillian A., Wilkinson, J. Mark, Zhai, Yanyan, Felson, David T., Ioannidis, John P.A., Loughlin, John, Metspalu, Andres, Meulenbelt, Ingrid, Stefansson, Kari, van Meurs, Joyce B., Zeggini, Eleftheria, Spector, Timothy D., and González, Antonio

Abstract

[Abstract] Objective: To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. Methods: A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10(-5) were considered significant. Results: SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10(-5) , odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06-1.17) and rs1241164 (P = 1.47 × 10(-5) , OR 0.82, 95% CI 0.74-0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10(-5) , OR 0.87, 95% CI 0.82-0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10(-5) , OR 0.85, 95% CI 0.79-0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. Conclusion: Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated.

Published
2013

31. A Meta-Analysis of Genome-Wide Association Studies Identifies Novel Variants Associated with Osteoarthritis of the Hip

Author

Evangelou, Evangelos, Kerkhof, Hanneke J., Styrkarsdottir, Unnur, Ntzani, Evangelia E., Bos, Steffan D., Esko, Tonu, Evans, Daniel S., Metrustry, Sarah, Panoutsopoulou, Kalliope, Ramos, Yolande F. M., Thorleifsson, Gudmar, Tsilidis, Konstantinos K., Arden, Nigel, Aslam, Nadim, Bellamy, Nicholas, Birrell, Fraser, Blanco García, Francisco J, Carr, Andrew, Chapman, Kay, Day-Williams, Aaaron G., Deloukas, Panos, Doherty, Michael, Engström, Gunnar, Helgadottir, Hafdis T., Hofman, Albert, Ingvarsson, Thorvaldur, Jonsson, Helgi, Keis, Aime, Keurentjes, J. Christiaan, Kloppenburg, Margreet, Lind, Penelope A., McCaskie, Andrew, Martin, Nicholas G., Milani, Lili, Montgomery, Grant W., Nelissen, Rob G.H.H., Nevitt, Michael C., Nilsson, Peter M., Ollier, William E.R., Parimi, Neeta, Rai, Ashok, Ralston, Stuart H., Reed, Mike R., Riancho, José A., Rivadeneira, Fernando, Rodríguez-Fontenla, Cristina, Southam, Lorraine, Thorsteindottir, Unnur, Tsezou, Aspasia, Wallis, Gillian A., Wilkinson, J. Mark, González, Antonio, Lane, Nancy E., Lohmander, L. Stefan, Loughlin, John, Metspalu, Andres, Uitterlinden, André G., Jonsdottir, Ingileif, Stefansson, Kari, Slagboom, P. Eline, Zeggini, Eleftheria, Meulebelt, Ingrid, Ionnidis, John P.A., Spector, Tim D., van Meurs, Joyce B.J., Valdes, Ana M., Evangelou, Evangelos, Kerkhof, Hanneke J., Styrkarsdottir, Unnur, Ntzani, Evangelia E., Bos, Steffan D., Esko, Tonu, Evans, Daniel S., Metrustry, Sarah, Panoutsopoulou, Kalliope, Ramos, Yolande F. M., Thorleifsson, Gudmar, Tsilidis, Konstantinos K., Arden, Nigel, Aslam, Nadim, Bellamy, Nicholas, Birrell, Fraser, Blanco García, Francisco J, Carr, Andrew, Chapman, Kay, Day-Williams, Aaaron G., Deloukas, Panos, Doherty, Michael, Engström, Gunnar, Helgadottir, Hafdis T., Hofman, Albert, Ingvarsson, Thorvaldur, Jonsson, Helgi, Keis, Aime, Keurentjes, J. Christiaan, Kloppenburg, Margreet, Lind, Penelope A., McCaskie, Andrew, Martin, Nicholas G., Milani, Lili, Montgomery, Grant W., Nelissen, Rob G.H.H., Nevitt, Michael C., Nilsson, Peter M., Ollier, William E.R., Parimi, Neeta, Rai, Ashok, Ralston, Stuart H., Reed, Mike R., Riancho, José A., Rivadeneira, Fernando, Rodríguez-Fontenla, Cristina, Southam, Lorraine, Thorsteindottir, Unnur, Tsezou, Aspasia, Wallis, Gillian A., Wilkinson, J. Mark, González, Antonio, Lane, Nancy E., Lohmander, L. Stefan, Loughlin, John, Metspalu, Andres, Uitterlinden, André G., Jonsdottir, Ingileif, Stefansson, Kari, Slagboom, P. Eline, Zeggini, Eleftheria, Meulebelt, Ingrid, Ionnidis, John P.A., Spector, Tim D., van Meurs, Joyce B.J., and Valdes, Ana M.

Abstract

[Abstract] OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. METHODS: We performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. RESULTS: We accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis). CONCLUSIONS: Novel genetic loci for hip OA were found in this meta-analysis of GWAS.

Published
2013

32. A Variant in MCF2L Is Associated with Osteoarthritis

Author

Day-Williams, Aaron G., primary, Southam, Lorraine, additional, Panoutsopoulou, Kalliope, additional, Rayner, Nigel W., additional, Esko, Tonu, additional, Estrada, Karol, additional, Helgadottir, Hafdis T., additional, Hofman, Albert, additional, Ingvarsson, Throvaldur, additional, Jonsson, Helgi, additional, Keis, Aime, additional, Kerkhof, Hanneke J.M., additional, Thorleifsson, Gudmar, additional, Arden, Nigel K., additional, Carr, Andrew, additional, Chapman, Kay, additional, Deloukas, Panos, additional, Loughlin, John, additional, McCaskie, Andrew, additional, Ollier, William E.R., additional, Ralston, Stuart H., additional, Spector, Timothy D., additional, Wallis, Gillian A., additional, Wilkinson, J. Mark, additional, Aslam, Nadim, additional, Birell, Fraser, additional, Carluke, Ian, additional, Joseph, John, additional, Rai, Ashok, additional, Reed, Mike, additional, Walker, Kirsten, additional, Doherty, Sally A., additional, Jonsdottir, Ingileif, additional, Maciewicz, Rose A., additional, Muir, Kenneth R., additional, Metspalu, Andres, additional, Rivadeneira, Fernando, additional, Stefansson, Kari, additional, Styrkarsdottir, Unnur, additional, Uitterlinden, Andre G., additional, van Meurs, Joyce B.J., additional, Zhang, Weiya, additional, Valdes, Ana M., additional, Doherty, Michael, additional, and Zeggini, Eleftheria, additional

Published
2011
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47. Positive selection in autoimmunity: Abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis

Author

Albani, Salvatore, primary, Keystone, Edward C., additional, Nelson, J. Lee, additional, Ollier, William E.R., additional, La Cava, Antonio, additional, Montemayor, Ann C., additional, Weber, Deborah A., additional, Montecucco, Carlomaurizio, additional, Martini, Alberto, additional, and Carson, Dennis A., additional

Published
1995
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49. Genome-wide association study identifies 74 loci associated with educational attainment

Author

Okbay, Aysu, Beauchamp, Jonathan P., Fontana, Mark A., Lee, James J., Pers, Tune H., Rietveld, Cornelius A., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Meddens, S. Fleur W., Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Abdellaoui, Abdel, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Furlotte, Nicholas A., Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, van der Lee, Sven J., de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., van der Most, Peter J., Oldmeadow, Christopher, Payton, Antony, Pervjakova, Natalia, Peyrot, Wouter J., Qian, Yong, Raitakari, Olli, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate, Teumer, Alexander, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Westra, Harm-Jan, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klaus, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eibich, Peter, Eisele, Lewin, Eklund, Niina, Evans68, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Joshi, Peter K., Jugessur, Astanand, Kaakinen, Marika A., Kähönen, Mika, Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A.L.M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Kutalik, Zoltan, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C.M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Meddens, Gerardus A., McMahon, George, Meisinger, Christa, Meitinger, Thomas, Milaneschi, Yusplitri, Milani, Lili, Montgomery, Grant W., Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E.R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, van Rooij, Frank J.A., Venturini, Cristina, Vinkhuyzen, Anna A.E., Völker, Uwe, Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johannes, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klaus, Bertram, Lars, Bisgaard, Hans, Boomsma, Dorret I., Borecki, Ingrid B., Bultmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., van Duijn, Cornelia M., Eriksson, Johan G., Franke, Barbara, Franke, Lude, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J.F., Gudnason, Vilmundur, van der Harst, Pim, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L.R., Lehtimäki, Terho, Lehrer, Steven F., Magnusson, Patrik K.E., Martin, Nicholas G., McGue, Matt, Metspalu, Andres, Pendleton, Neil, Penninx, Brenda W.J.H., Perola, Markus, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I.A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Tung, Joyce Y., Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Yang, Jian, Johannesson, Magnus, Visscher, Peter M., Esko, Tõnu, Koellinger, Philipp D., Cesarini, David, and Benjamin, Daniel J.

Abstract

Summary Educational attainment (EA) is strongly influenced by social and other environmental factors, but genetic factors are also estimated to account for at least 20% of the variation across individuals1. We report the results of a genome-wide association study (GWAS) for EA that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication in an independent sample of 111,349 individuals from the UK Biobank. We now identify 74 genome-wide significant loci associated with number of years of schooling completed. Single-nucleotide polymorphisms (SNPs) associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioral phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because EA is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric disease.

Published
2016
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50. Dogslife: A web-based longitudinal study of Labrador Retriever health in the UK.

Author

Clements, Dylan N., Handel, Ian G., Rose, Erica, Querry, Damon, Pugh, Carys A., Ollier, William E.R., Morgan, Kenton L., Kennedy, Lorna J., Sampson, Jeffery, Summers, Kim M., and de Bronsvoort, B. Mark C.

Subjects
LABRADOR retriever, HEALTH, DISEASES, COHORT analysis
Abstract

Background: Dogslife is the first large-scale internet-based longitudinal study of canine health. The study has been designed to examine how environmental and genetic factors influence the health and development of a birth cohort of UK-based pedigree Labrador Retrievers. Results: In the first 12 months of the study 1,407 Kennel Club (KC) registered eligible dogs were recruited, at a mean age of 119 days of age (SD 69 days, range 3 days - 504 days). Recruitment rates varied depending upon the study team's ability to contact owners. Where owners authorised the provision of contact details 8.4% of dogs were recruited compared to 1.3% where no direct contact was possible. The proportion of dogs recruited was higher for owners who transferred the registration of their puppy from the breeder to themselves with the KC, and for owners who were sent an e-mail or postcard requesting participation in the project. Compliance with monthly updates was highly variable. For the 280 dogs that were aged 400 days or more on the 30th June 2011, we estimated between 39% and 45% of owners were still actively involved in the project. Initial evaluation suggests that the cohort is representative of the general population of the KC registered Labrador Retrievers eligible to enrol with the project. Clinical signs of illnesses were reported in 44.3% of Labrador Retrievers registered with Dogslife (median age of first illness 138 days), although only 44.1% of these resulted in a veterinary presentation (median age 316 days). Conclusions: The web-based platform has enabled the recruitment of a representative population of KC registered Labrador Retrievers, providing the first large-scale longitudinal population-based study of dog health. The use of multiple different methods (e-mail, post and telephone) of contact with dog owners was essential to maximise recruitment and retention of the cohort [ABSTRACT FROM AUTHOR]

Published
2013
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