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101. Efficacy of intra-articular injections of platelet-rich plasma as a symptom- and disease-modifying treatment for knee osteoarthritis - the RESTORE trial protocol

Author: Paterson, KL, Hunter, DJ, Metcalf, BR, Eyles, J, Duong, V, Kazsa, J, Wang, Y, Buchbinder, R, Cicuttini, F, Forbes, A, Harris, A, Yu, SP, Wang, BH, Connell, D, Linklater, J, Bennell, KL, Paterson, KL, Hunter, DJ, Metcalf, BR, Eyles, J, Duong, V, Kazsa, J, Wang, Y, Buchbinder, R, Cicuttini, F, Forbes, A, Harris, A, Yu, SP, Wang, BH, Connell, D, Linklater, J, and Bennell, KL
Abstract: BACKGROUND: Knee osteoarthritis (OA) causes substantial pain, physical dysfunction and impaired quality of life. There is no cure for knee OA, and for some people, the disease may involve progressive symptomatic and structural deterioration over time. Platelet-rich plasma (PRP) is a therapeutic agent that aims to address underlying biological processes responsible for OA pathogenesis. As such, it has the potential to improve both symptoms and joint structure. The aim of this clinical trial is to determine whether a series of injections of PRP into the knee joint will lead to a significantly greater reduction in knee pain, and less loss of medial tibial cartilage volume over 12 months when compared to a series of placebo saline injections in people with knee OA. METHODS: This will be a two-group, superiority, randomised, participant-, interventionist- and assessor-blinded, placebo-controlled trial. Two hundred and eighty-eight participants aged over 50 years with painful knee OA and mild to moderate structural change on x-ray (Kellgren and Lawrence grade 2 and 3) will be randomly allocated to receive either three PRP injections or three normal saline injections into the knee joint at weekly intervals. The primary outcomes will be 12-month change in average overall knee pain severity (numeric rating scale) and medial tibial cartilage volume (magnetic resonance imaging (MRI)). Secondary outcomes include additional measures of knee pain and other symptoms, function in daily living and sport and recreation, quality of life, participant-perceived global ratings of change, and other MRI structural outcomes including meniscal and cartilage morphology, synovitis, effusion, bone marrow lesions and cartilage defects. A range of additional measures will be recorded, and a separate health economic evaluation will be performed. DISCUSSION: The findings from this study will help determine whether PRP improves both clinical and structural knee OA outcomes over 12 months when compar
Published: 2018

102. Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY

Author: Hunter, DJ, Hinman, RS, Bowden, JL, Egerton, T, Briggs, AM, Bunker, SJ, Kasza, J, Forbes, AB, French, SD, Pirotta, M, Schofield, DJ, Zwar, NA, Bennell, KL, Hunter, DJ, Hinman, RS, Bowden, JL, Egerton, T, Briggs, AM, Bunker, SJ, Kasza, J, Forbes, AB, French, SD, Pirotta, M, Schofield, DJ, Zwar, NA, and Bennell, KL
Abstract: BACKGROUND: To increase the uptake of key clinical recommendations for non-surgical management of knee osteoarthritis (OA) and improve patient outcomes, we developed a new model of service delivery (PARTNER model) and an intervention to implement the model in the Australian primary care setting. We will evaluate the effectiveness and cost-effectiveness of this model compared to usual general practice care. METHODS: We will conduct a mixed-methods study, including a two-arm, cluster randomised controlled trial, with quantitative, qualitative and economic evaluations. We will recruit 44 general practices and 572 patients with knee OA in urban and regional practices in Victoria and New South Wales. The interventions will target both general practitioners (GPs) and their patients at the practice level. Practices will be randomised at a 1:1 ratio. Patients will be recruited if they are aged ≥45 years and have experienced knee pain ≥4/10 on a numerical rating scale for more than three months. Outcomes are self-reported, patient-level validated measures with the primary outcomes being change in pain and function at 12 months. Secondary outcomes will be assessed at 6 and 12 months. The implementation intervention will support and provide education to intervention group GPs to deliver effective management for patients with knee OA using tailored online training and electronic medical record support. Participants with knee OA will have an initial GP visit to confirm their diagnosis and receive management according to GP intervention or control group allocation. As part of the intervention group GP management, participants with knee OA will be referred to a centralised multidisciplinary service: the PARTNER Care Support Team (CST). The CST will be trained in behaviour change support and evidence-based knee OA management. They will work with patients to develop a collaborative action plan focussed on key self-management behaviours, and communicate with the patients' GPs. Patien
Published: 2018

103. Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY (vol 19, 132, 2018)

Author: Hunter, DJ, Hinman, RS, Bowden, JL, Egerton, T, Briggs, AM, Bunker, SJ, Kasza, J, Forbes, AB, French, SD, Pirotta, M, Schofield, DJ, Zwar, NA, Bennell, KL, Hunter, DJ, Hinman, RS, Bowden, JL, Egerton, T, Briggs, AM, Bunker, SJ, Kasza, J, Forbes, AB, French, SD, Pirotta, M, Schofield, DJ, Zwar, NA, and Bennell, KL
Abstract: After the publication of this protocol [1], our collaborator Prima Health solutions advised us of their intent to withdraw from the study.
Published: 2018

104. A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer: Results from the Breast and Prostate Cancer Cohort Consortium

Author: Barrdahl, M, Canzian, F, Gaudet, MM, Gapstur, SM, Trichopoulou, A, Tsilidis, K, van Gils, CH, Borgquist, S, Weiderpass, E, Khaw, K-T, Giles, GG, Milne, RL, Le Marchand, L, Haiman, C, Lindstrom, S, Kraft, P, Hunter, DJ, Ziegler, R, Chanock, SJ, Yang, XR, Buring, JE, Lee, I-M, Kaaks, R, Campa, D, Barrdahl, M, Canzian, F, Gaudet, MM, Gapstur, SM, Trichopoulou, A, Tsilidis, K, van Gils, CH, Borgquist, S, Weiderpass, E, Khaw, K-T, Giles, GG, Milne, RL, Le Marchand, L, Haiman, C, Lindstrom, S, Kraft, P, Hunter, DJ, Ziegler, R, Chanock, SJ, Yang, XR, Buring, JE, Lee, I-M, Kaaks, R, and Campa, D
Abstract: We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin-like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A-rs2382112 (ORhom = 3.05, 95%CI = 1.72-5.44, Phom = 1.47 × 10-4 ), MAST2-rs12124649 (ORhom = 1.73, 95% CI =1.18-2.54, Phom = 5.24 × 10-3 ), and INSR-rs10500204 (ORhom = 1.96, 95% CI = 1.44-2.67, Phom =1.68 × 10-5 ) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR-rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case-only analyses using the homozygous minor versus homozygous major model (ORhom = 1.78, 95% CI = 1.30-2.44, Phom = 3.23 × 10-4 ). The SNP INSR-rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A-allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further.
Published: 2018

105. Identification of nine new susceptibility loci for endometrial cancer

Author: O'Mara, TA, Glubb, DM, Amant, F, Annibali, D, Ashton, K, Attia, J, Auer, PL, Beckmann, MW, Black, A, Bolla, MK, Brauch, H, Brenner, H, Brinton, L, Buchanan, DD, Burwinkel, B, Chang-Claude, J, Chanock, SJ, Chen, C, Chen, MM, Cheng, THT, Clarke, CL, Clendenning, M, Cook, LS, Couch, FJ, Cox, A, Crous-Bous, M, Czene, K, Day, F, Dennis, J, Depreeuw, J, Doherty, JA, Dork, T, Dowdy, SC, Duerst, M, Ekici, AB, Fasching, PA, Fridley, BL, Friedenreich, CM, Fritschi, L, Fung, J, Garcia-Closas, M, Gaudet, MM, Giles, GG, Goode, EL, Gorman, M, Haiman, CA, Hall, P, Hankison, SE, Healey, CS, Hein, A, Hillemanns, P, Hodgson, S, Hoivik, EA, Holliday, EG, Hopper, JL, Hunter, DJ, Jones, A, Krakstad, C, Kristensen, VN, Lambrechts, D, Le Marchand, L, Liang, X, Lindblom, A, Lissowska, J, Long, J, Lu, L, Magliocco, AM, Martin, L, McEvoy, M, Meindl, A, Michailidou, K, Milne, RL, Mints, M, Montgomery, GW, Nassir, R, Olsson, H, Orlow, I, Otton, G, Palles, C, Perry, JRB, Peto, J, Pooler, L, Prescott, J, Proietto, T, Rebbeck, TR, Risch, HA, Rogers, PAW, Ruebner, M, Runnebaum, I, Sacerdote, C, Sarto, GE, Schumacher, F, Scott, RJ, Setiawan, VW, Shah, M, Sheng, X, Shu, X-O, Southey, MC, Swerdlow, AJ, Tham, E, Trovik, J, Turman, C, Tyrer, JP, Vachon, C, Vanden Berg, D, Vanderstichele, A, Wang, Z, Webb, PM, Wentzensen, N, Werner, HMJ, Winham, SJ, Wolk, A, Xia, L, Xiang, Y-B, Yang, HP, Yu, H, Zheng, W, Pharoah, PDP, Dunning, AM, Kraft, P, De Vivo, I, Tomlinson, I, Easton, DF, Spurdle, AB, Thompson, DJ, O'Mara, TA, Glubb, DM, Amant, F, Annibali, D, Ashton, K, Attia, J, Auer, PL, Beckmann, MW, Black, A, Bolla, MK, Brauch, H, Brenner, H, Brinton, L, Buchanan, DD, Burwinkel, B, Chang-Claude, J, Chanock, SJ, Chen, C, Chen, MM, Cheng, THT, Clarke, CL, Clendenning, M, Cook, LS, Couch, FJ, Cox, A, Crous-Bous, M, Czene, K, Day, F, Dennis, J, Depreeuw, J, Doherty, JA, Dork, T, Dowdy, SC, Duerst, M, Ekici, AB, Fasching, PA, Fridley, BL, Friedenreich, CM, Fritschi, L, Fung, J, Garcia-Closas, M, Gaudet, MM, Giles, GG, Goode, EL, Gorman, M, Haiman, CA, Hall, P, Hankison, SE, Healey, CS, Hein, A, Hillemanns, P, Hodgson, S, Hoivik, EA, Holliday, EG, Hopper, JL, Hunter, DJ, Jones, A, Krakstad, C, Kristensen, VN, Lambrechts, D, Le Marchand, L, Liang, X, Lindblom, A, Lissowska, J, Long, J, Lu, L, Magliocco, AM, Martin, L, McEvoy, M, Meindl, A, Michailidou, K, Milne, RL, Mints, M, Montgomery, GW, Nassir, R, Olsson, H, Orlow, I, Otton, G, Palles, C, Perry, JRB, Peto, J, Pooler, L, Prescott, J, Proietto, T, Rebbeck, TR, Risch, HA, Rogers, PAW, Ruebner, M, Runnebaum, I, Sacerdote, C, Sarto, GE, Schumacher, F, Scott, RJ, Setiawan, VW, Shah, M, Sheng, X, Shu, X-O, Southey, MC, Swerdlow, AJ, Tham, E, Trovik, J, Turman, C, Tyrer, JP, Vachon, C, Vanden Berg, D, Vanderstichele, A, Wang, Z, Webb, PM, Wentzensen, N, Werner, HMJ, Winham, SJ, Wolk, A, Xia, L, Xiang, Y-B, Yang, HP, Yu, H, Zheng, W, Pharoah, PDP, Dunning, AM, Kraft, P, De Vivo, I, Tomlinson, I, Easton, DF, Spurdle, AB, and Thompson, DJ
Abstract: Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
Published: 2018

106. Directors of public health as 'a protected species': qualitative study of the changing role of public health professionals in England following the 2013 reforms.

Author: Jehu, LM, Visram, S, Marks, L, Hunter, DJ, Davis, H, Mason, A, Liu, D, Smithson, J, Jehu, LM, Visram, S, Marks, L, Hunter, DJ, Davis, H, Mason, A, Liu, D, and Smithson, J
Abstract: Background: The Health and Social Care Act 2012 gave councils in England responsibility for improving the health of their populations. Public health teams were transferred from the National Health Service (NHS), accompanied by a ring-fenced public health grant. This study examines the changing role of these teams within local government. Methods: In-depth case study research was conducted within 10 heterogeneous councils. Initial interviews (n = 90) were carried out between October 2015 and March 2016, with follow-up interviews (n = 21) 12 months later. Interviewees included elected members, directors of public health (DsPH) and other local authority officers, plus representatives from NHS commissioners, the voluntary sector and Healthwatch. Results: Councils welcomed the contribution of public health professionals, but this was balanced against competing demands for financial resources and democratic leverage. DsPH-seen by some as a 'protected species'-were relying increasingly on negotiating and networking skills to fulfil their role. Both the development of the existing specialist public health workforce and recruitment to, and development of, the future workforce were uncertain. This poses both threats and opportunities. Conclusions: Currently the need for staff to retain specialist skills and maintain UKPH registration is respected. However, action is needed to address how future public health professionals operating within local government will be recruited and developed.
Published: 2018

107. Large-scale transcriptome-wide association study identifies new prostate cancer risk regions

Author: Mancuso, N, Gayther, S, Dominguez, MG, Roobol - Bouts, Monique, Menegaux, F, Khaw, KTH, Cannon-Albright, L, Pandha, H, Thibodeau, SN, Hunter, DJ, Kraft, P, Mancuso, N, Gayther, S, Dominguez, MG, Roobol - Bouts, Monique, Menegaux, F, Khaw, KTH, Cannon-Albright, L, Pandha, H, Thibodeau, SN, Hunter, DJ, and Kraft, P
Published: 2018

108. Efficacy of bisphosphonates in specific knee osteoarthritis subpopulations: protocol for an OA Trial Bank systematic review and individual patient data meta-analysis

Author: Deveza, LA, Bierma - Zeinstra, Sita, van Spil, WE, Oo, WM, Saragiotto, B T, Neogi, T, van Middelkoop, Marienke, Hunter, DJ, Deveza, LA, Bierma - Zeinstra, Sita, van Spil, WE, Oo, WM, Saragiotto, B T, Neogi, T, van Middelkoop, Marienke, and Hunter, DJ
Published: 2018

109. A call for action to establish a research agenda for building a future health workforce in Europe

Author: Kuhlmann, E, Batenburg, R, Wismar, M, Dussault, G, Maier, CB, Glinos, IA, Azzopardi-Muscat, N, Bond, C, Burau, V, Correia, T, Groenewegen, PP, Hansen, J, Hunter, DJ, Khan, U, Kluge, HH, Kroezen, Marieke, Leone, C, Santric-Milicevic, M, Sermeus, W, Ungureanu, M, Kuhlmann, E, Batenburg, R, Wismar, M, Dussault, G, Maier, CB, Glinos, IA, Azzopardi-Muscat, N, Bond, C, Burau, V, Correia, T, Groenewegen, PP, Hansen, J, Hunter, DJ, Khan, U, Kluge, HH, Kroezen, Marieke, Leone, C, Santric-Milicevic, M, Sermeus, W, and Ungureanu, M
Published: 2018

110. Association of weather factors with the risk of pain exacerbations in people with hip osteoarthritis.

Author: Fu, K, Metcalf, B, Bennell, KL, Zhang, Y, Deveza, LA, Robbins, SR, Ferreira, ML, Hunter, DJ, Bennell, K L, Deveza, L A, Robbins, S R, Ferreira, M L, and Hunter, D J
Subjects: METEOROLOGICAL databases, ATMOSPHERIC pressure, WEATHER, HUMIDITY, PAIN, HIP osteoarthritis
Abstract: Objectives: Our objective was to evaluate the association of weather factors with the risk of pain exacerbations in people with symptomatic hip osteoarthritis (OA). Method: Eligible participants with symptomatic hip OA were instructed to log on to the study website and complete questionnaires every 10 days and additionally whenever they considered they were experiencing a pain exacerbation (case period) during the 90 day follow-up. Pain exacerbation was defined as an increase of two points in pain intensity on an 11-point numeric rating scale (0-10) during the follow-up compared with baseline. Each case period was anchored to four control periods within a 35 day interval using a time-stratified approach. Weather data were obtained for both periods from the publicly available meteorological database of the Australian Bureau of Meteorology. We examined the association of weather factors across 72 h before the index date with the risk of pain exacerbation, using conditional logistic regression. Results: Among 252 participants recruited, 129 participants had at least one episode of pain exacerbation and were included in the analysis. A significant dose-response relationship was found between average daily temperature variation in the prior 72 h and risk of pain exacerbations (p = 0.04 for linear trend). There was no significant association between maximum daily temperature, minimum daily temperature, relative humidity, precipitation, or barometric pressure and hip pain exacerbations. Conclusion: The overall results suggest that only daily temperature variation among different weather factors was associated with hip pain exacerbations in people with symptomatic hip OA. [ABSTRACT FROM AUTHOR]
Published: 2021
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111. Erratum: Genomewide meta-analysis identifies loci associated with IGF-I and IGEBP-3 levels with impact on age-related traits

Author: Teumer, A, Qi, Q, Nethander, M, Aschard, H, Bandinelli, S, Beekman, M, Berndt, SI, Bidlingmaier, M, Broer, L, Cappola, A, Ceda, GP, Chanock, S, Chen, M-H, Chen, TC, Chen, Y-DI, Chung, J, Miglianico, DGF, Eriksson, J, Ferrucci, L, Friedrich, N, Gnewuch, C, Goodarzi, MO, Grarup, N, Guo, T, Hammer, E, Hayes, RB, Hicks, AA, Hofman, A, Houwing-Duistermaat, JJ, Hu, F, Hunter, DJ, Husemoen, LL, Isaacs, A, Jacobs, KB, Janssen, JAMJL, Jansson, J-O, Jehmlich, N, Johnson, S, Juul, A, Karlsson, M, Kilpelainen, TO, Kovacs, P, Kraft, P, Li, C, Linneberg, A, Liu, Y, Loos, RJF, Lorentzon, M, Lu, Y, Maggio, M, Magi, R, Meigs, J, Mellstrom, D, Nauck, M, Newman, AB, Pollak, MN, Pramstaller, PP, Prokopenko, I, Psaty, BM, Reincke, M, Rimm, EB, Rotter, JI, Pierre, SA, Schurmann, C, Seshadri, S, Sjogren, K, Slagboom, PE, Strickler, HD, Stumvoll, M, Suh, Y, Sun, Q, Zhang, C, Svensson, J, Tanaka, T, Tare, A, Tonjes, A, Uh, H-W, Van Duijn, CM, Van Heemst, D, Vandenput, L, Vasan, RS, Volker, U, Willems, SM, Ohlsson, C, Wallaschofski, H, and Kaplan, RC
Subjects: Science & Technology, Geriatrics & Gerontology, Cell Biology, 11 Medical And Health Sciences, 06 Biological Sciences, Life Sciences & Biomedicine, Developmental Biology
Abstract: In the article, ‘Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits’, the published Table 1 was incorrect, due to an error.
Published: 2017

112. Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148

Author: Fang, J, Jia, J, Makowski, M, Xu, M, Wang, Z, Zhang, T, Hoskins, Jw, Choi, J, Han, Y, Zhang, M, Thomas, J, Kovacs, M, Collins, I, Dzyadyk, M, Thompson, A, O'Neill, M, Das, S, Lan, Q, Koster, R, Solomon, Rs, Kraft, P, Wolpin, Bm, Jansen, Pwtc, Olson, S, Mcglynn, Ka, Kanetsky, Pa, Chatterjee, N, Barrett, Jh, Dunning, Am, Taylor, Jc, Newton Bishop, Ja, Bishop, Dt, Andresson, T, Petersen, Gm, Amos, Ci, Iles, Mm, Nathanson, Kl, Landi, Mt, Vermeulen, M, Brown, Km, Amundadottir, Lt, Canzian, F, Kooperberg, C, Arslan, Aa, Bracci, Pm, Buring, J, Duell, Ej, Gallinger, S, Jacobs, Ej, Kamineni, A, Van Den Eeden, S, Klein, Ap, Kolonel, Ln, Li, D, Olson, Sh, Risch, Ha, Sesso, Hd, Visvanathan, K, Zheng, W, Albanes, D, Austin, Ma, Boutron Ruault, Mc, Bueno de Mesquita, Hb, Cotterchio, M, Gaziano, Jm, Giovannucci, El, Goggins, M, Gross, M, Hassan, M, Helzlsouer, Kj, Holly, Ea, Hunter, Dj, Jenab, M, Kaaks, R, Key, Tj, Khaw, Kt, Krogh, V, Kurtz, Rc, Lacroix, A, Le Marchand, L, Mannisto, S, Patel, Av, Peeters, Phm, Riboli, E, Shu, Xo, Sund, M, Thornquist, M, Tjønneland, A, Tobias, Gs, Trichopoulos, D, Wactawski Wende, J, Yu, H, Yu, K, Zeleniuch Jacquotte, A, Hoover, R, Hartge, P, Fuchs, C, Chanock, Sj, Stevens, V, Caporaso, Ne, Brennan, P, Mckay, J, Wu, X, Hung, Rj, Mclaughlin, Jr, Bickeboller, H, Risch, A, Wichmann, E, Houlston, R, Mann, G, Hopper, J, Aitken, J, Armstrong, B, Giles, G, Holland, E, Kefford, R, Cust, A, Jenkins, M, Schmid, H, Puig, S, Aguilera, P, Badenas, C, Barreiro, A, Carrera, C, Gabriel, D, Xavier, Pg, Iglesias Garcia, P, Malvehy, J, Mila, M, Pigem, R, Potrony, M, Batille, Ja, Marti, Gt, Hayward, N, Martin, N, Montgomery, G, Duffy, D, Whiteman, D, Gregor, Sm, Calista, D, Landi, G, Minghetti, P, Arcangeli, F, Bertazzi, Pa, Ghiorzo, Paola, Bianchi, Giovanna, Pastorino, Lorenza, Bruno, William, Andreotti, Virginia, Queirolo, P, Spagnolo, Francesco, Mackie, R, Lang, J, Gruis, N, van Nieuwpoort, Fa, Out, C, Bergman, W, Kukutsch, N, Bavinck, Jnb, Bakker, B, van der Stoep, N, Ter Huurne, J, van der Rhee, H, Bekkenk, M, Snels, D, van Praag, M, Brochez, L, Gerritsen, R, Crijns, M, Vasen, H, Janssen, B, Ingvar, C, Olsson, H, Jonsson, G, Borg, A, Harbst, K, Nielsen, K, Zander, As, Molvern, A, Helsing, P, Andresen, Pa, Rootwelt, H, Akslen, La, Bressac de Paillerets, B, Demenais, F, Avril, Mf, Chaudru, V, Jeannin, P, Lesueur, F, Maubec, E, Mohamdi, H, Bossard, M, Vaysse, A, Boitier, F, Caron, O, Caux, F, Dalle, S, Dereure, O, Leroux, D, Martin, L, Mateus, C, Robert, C, Stoppa Lyonnet, D, Thomas, L, Wierzbicka, E, Elder, D, Ming, M, Mitra, N, Debniak, T, Lubinski, J, Hocevar, M, Novakovic, S, Peric, B, Skerl, P, Hansson, J, Hoiom, V, Freidman, E, Azizi, E, Baron Epel, O, Scope, A, Pavlotsky, F, Cohen Manheim, I, Laitman, Y, Harland, M, Randerson Moor, J, Laye, J, Davies, J, Nsengimana, J, O'Shea, S, Chan, M, Gascoyne, J, Tucker, Ma, Goldstein, Am, and Yang, X. r.
Subjects: 0301 basic medicine, Male, Lung Neoplasms, Skin Neoplasms, General Physics and Astronomy, Genome-wide association study, VARIANTS, Histones, Skin cancer, RNA, Small Interfering, Melanoma, Telomerase, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Pancreas cancer, Regulation of gene expression, Genetics, Zinc finger, Gene knockdown, Multidisciplinary, Proteomics and Chromatin Biology, TRICL Consortium, Chromosome Mapping, GenoMEL Consortium, PANCREATIC-CANCER, Multidisciplinary Sciences, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Science & Technology - Other Topics, Chromosomes, Human, Pair 5, Female, Lung cancer, Signal Transduction, SUSCEPTIBILITY LOCI, Science, Locus (genetics), Single-nucleotide polymorphism, PROMOTES GROWTH, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, LUNG-CANCER, Testicular Neoplasms, Cell Line, Tumor, MD Multidisciplinary, Humans, Genetic Predisposition to Disease, QUANTITATIVE PROTEOMICS, GENOME-WIDE ASSOCIATION, Gene, PanScan Consortium, Càncer de pell, Càncer de pàncrees, Alleles, Science & Technology, Kirurgi, HUMAN-CELLS, Telomere Homeostasis, Correction, General Chemistry, Molecular biology, TERT-CLPTM1L LOCUS, Telomere, Pancreatic Neoplasms, 030104 developmental biology, Genetic Loci, TELOMERE LENGTH, Càncer de pulmó, Surgery, Genètica, Genome-Wide Association Study, Transcription Factors
Abstract: Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele., Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.
Published: 2017

113. Body mass index and breast cancer survival: a Mendelian randomization analysis

Author: Guo, Q, Burgess, S, Turman, C, Bolla, MK, Wang, Q, Lush, M, Abraham, J, Aittomäki, K, Andrulis, IL, Apicella, C, Arndt, V, Barrdahl, M, Benitez, J, Berg, CD, Blomqvist, C, Bojesen, SE, Bonanni, B, Brand, JS, Brenner, H, Broeks, A, Burwinkel, B, Caldas, C, Campa, D, Canzian, F, Chang-Claude, J, Chanock, SJ, Chin, S-F, Couch, FJ, Cox, A, Cross, SS, Cybulski, C, Czene, K, Darabi, H, Devilee, P, Diver, WR, Dunning, AM, Earl, HM, Eccles, DM, Ekici, AB, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Flesch-Janys, D, Flyger, H, Gapstur, SM, Gaudet, MM, Giles, GG, Glendon, G, Grip, M, Gronwald, J, Haeberle, L, Haiman, CA, Hall, P, Hamann, U, Hankinson, S, Hartikainen, JM, Hein, A, Hiller, L, Hogervorst, FB, Holleczek, B, Hooning, MJ, Hoover, RN, Humphreys, K, Hunter, DJ, Hüsing, A, Jakubowska, A, Jukkola-Vuorinen, A, Kaaks, R, Kabisch, M, Kataja, V, Investigators, Kconfab/Aocs, Knight, JA, Koppert, LB, Kosma, V-M, Kristensen, VN, Lambrechts, D, Le Marchand, L, Li, J, Lindblom, A, Lindström, S, Lissowska, J, Lubinski, J, Machiela, MJ, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Martens, JWM, McLean, C, Menéndez, P, Milne, RL, Mulligan, A, Muranen, TA, Nevanlinna, H, Neven, P, Nielsen, SF, Nordestgaard, BG, Olson, JE, Perez, JIA, Peterlongo, P, Phillips, K-A, Poole, CJ, Pylkäs, K, Radice, P, Rahman, N, Rüdiger, T, Rudolph, A, Sawyer, EJ, Schumacher, F, Seibold, P, Seynaeve, C, Shah, M, Smeets, A, Southey, MC, Tollenaar, RAEM, Tomlinson, I, Tsimiklis, H, Ulmer, H-U, Vachon, C, Van Den Ouweland, AMW, Veer, LJ, Wildiers, H, Willett, W, Winqvist, R, Zamora, MP, Chenevix-Trench, G, Dörk, T, Easton, DF, García-Closas, M, Kraft, P, Hopper, JL, Zheng, W, Schmidt, MK, Pharoah, PDP, Medical Oncology, and Surgery
Subjects: Genetic Variation, Breast Neoplasms, Mendelian Randomization Analysis, Body mass index, Breast cancer survival, Epidemiology, Genetics, Mendelian randomization, Polymorphism, Single Nucleotide, Risk Assessment, Survival Analysis, White People, Causality, Europe, RC0254, Meta-Analysis as Topic, Receptors, Estrogen, SDG 3 - Good Health and Well-being, Risk Factors, breast cancer survival, Humans, Female, epidemiology, genetics, Cancer
Abstract: Background There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. Methods We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01–1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89–1.13, P = 0.95). Conclusions Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.
Published: 2017

114. Biological interpretation of genome-wide association studies using predicted gene functions

Author: Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L, Chu AY, Estrada K, Luan J, Kutalik Z, Amin N, Buchkovich ML, Croteau Chonka DC, Day FR, Duan Y, Fall T, Fehrmann R, Ferreira T, Jackson AU, Karjalainen J, Lo KS, Locke AE, Mägi R, Mihailov E, Porcu E, Randall JC, Scherag A, Vinkhuyzen AA, Winkler TW, Workalemahu T, Zhao JH, Absher D, Albrecht E, Anderson D, Baron J, Beekman M, Demirkan A, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Fraser RM, Goel A, Gong J, Justice E, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Mangino M, Mateo Leach I, Medina Gomez C, Nalls MA, Nyholt DR, Palmer CD, Pasko D, Pechlivanis S, Prokopenko I, Ried JS, Ripke S, Shungin D, Stancáková A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Setten J, Van Vliet Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Afzal U, Ärnlöv J, Arscott GM, Bandinelli S, Barrett A, Bellis C, Bennett AJ, Berne C, Blüher M, Bolton JL, Böttcher Y, Boyd HA, Bruinenberg M, Buckley BM, Buyske S, Caspersen IH, Chines PS, Clarke R, Claudi Boehm S, Cooper M, Daw EW, De Jong A, Deelen J, Delgado G, Denny JC, Dhonukshe Rutten R, Dimitriou M, Doney AS, Dörr M, Eklund N, Eury E, Folkersen L, Garcia ME, Geller F, Giedraitis V, Go AS, Grallert H, Grammer TB, Gräßler J, Grönberg H, de Groot LC, Groves CJ, Haessler J, Haller T, Hallmans G, Hannemann A, Hartman CA, Hassinen M, Hayward C, Heard Costa NL, Helmer Q, Hemani G, Henders AK, Hillege HL, Hlatky MA, Hoffmann W, Hoffmann P, Holmen O, Houwing Duistermaat JJ, Illig T, Isaacs A, James AL, Jeff J, Johansen B, Johansson Å, Jolley J, Juliusdottir T, Junttila J, Kho AN, Kinnunen L, Klopp N, Kocher T, Kratzer W, Lichtner P, Lind L, Lindström J, Lobbens S, Lorentzon M, Lu Y, Lyssenko V, Magnusson PK, Mahajan A, Maillard M, McArdle WL, McKenzie CA, McLachlan S, McLaren PJ, Menni C, Merger S, Milani L, 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Borecki IB, McCarthy MI, Metspalu A, Stefansson K, Uitterlinden AG, van Duijn CM, Willer CJ, Price AL, Lettre G, Loos RJ, Weedon MN, Ingelsson E, O'Connell JR, Abecasis GR, Chasman DI, Goddard ME, Visscher PM, Frayling T.M., Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Wood, AR., Esko, T., Yang, J., Vedantam, S., Pers, TH., Gustafsson, S., Chu, AY., Estrada, K., Luan£££Jian'an£££ J., Kutalik£££Zoltán£££ Z., Amin, N., Buchkovich, ML., Croteau-Chonka, DC., Day, FR., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, AU., Karjalainen, J., Lo, KS., Locke, AE., Mägi, R., Mihailov, E., Porcu, E., Randall, JC., Scherag, A., Vinkhuyzen, AA., Westra, HJ., Winkler, TW., Workalemahu, T., Zhao, JH., Absher, D., Albrecht, E., 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Garcia, ME., Geller, F., Giedraitis, V., Go, AS., Grallert, H., Grammer, TB., Gräßler, J., Grönberg, H., de Groot LC., Groves, CJ., Haessler, J., Haller, T., Hallmans, G., Hannemann, A., Hartman, CA., Hassinen, M., Hayward, C., Heard-Costa, NL., Helmer, Q., Hemani, G., Henders, AK., Hillege, HL., Hlatky, MA., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, JJ., Illig, T., Isaacs, A., James, AL., Jeff, J., Johansen, B., Johansson£££Åsa£££ Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, AN., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, PK., Mahajan, A., Maillard, M., McArdle, WL., McKenzie, CA., McLachlan, S., McLaren, PJ., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, KL., Morken, MA., Müller, G., Müller-Nurasyid, M., Musk, AW., Narisu, N., Nauck, M., Nolte, IM., Nöthen, MM., Oozageer, L., Pilz, S., Rayner, NW., Renstrom, F., Robertson, NR., Rose, LM., 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V., Samani, NJ., Saramies, J., Sarzynski, MA., Schwarz, PE., Sebert, S., Sever, P., Shuldiner, AR., Sinisalo, J., Steinthorsdottir, V., Stolk, RP., Tardif, JC., Tönjes, A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, MC., Amouyel, P., Asselbergs, FW., Assimes, TL., Bochud, M., Boehm, BO., Boerwinkle, E., Bottinger, EP., Bouchard, C., Cauchi, S., Chambers, JC., Chanock, SJ., Cooper, RS., de Bakker PI., Dedoussis, G., Ferrucci, L., Franks, PW., Froguel, P., Groop, LC., Haiman, CA., Hamsten, A., Hayes, MG., Hui, J., Hunter, DJ., Hveem, K., Jukema, JW., Kaplan, RC., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., Martin, NG., März, W., Melbye, M., Moebus, S., Munroe, PB., Njølstad, I., Oostra, BA., Palmer, CN., Pedersen, NL., Perola, M., Pérusse, L., Peters, U., Powell, JE., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, PM., Rivadeneira, F., Rotter, JI., Saaristo, TE., Saleheen, D., Schlessinger, D., Slagboom, PE., Snieder, H., Spector, TD., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., van der Harst, P., Völzke, H., Walker, M., Wareham, NJ., Watkins, H., Wichmann, HE., Wilson, JF., Zanen, P., Deloukas, P., Heid, IM., Lindgren, CM., Mohlke, KL., Speliotes, EK., Thorsteinsdottir, U., Barroso£££Inês£££ I., Fox, CS., North, KE., Strachan, DP., Beckmann, JS., Berndt, SI., Boehnke, M., Borecki, IB., McCarthy, MI., Metspalu, A., Stefansson, K., Uitterlinden, AG., van Duijn CM., Franke, L., Willer, CJ., Price, AL., Lettre, G., Loos, RJ., Weedon, MN., Ingelsson, E., O'Connell, JR., Abecasis, GR., Chasman, DI., Goddard, ME., Visscher, PM., Hirschhorn, JN., Frayling, TM., Clinicum, Jaakko Kaprio / Principal Investigator, Department of Public Health, Institute for Molecular Medicine Finland, Genetic Epidemiology, Pers, T, Karjalainen, J, Chan, Y, Westra, H, Wood, A, Yang, J, Lui, J, Vedantam, S, Gustafsson, S, Esko, T, Frayling, T, Speliotes, E, Boehnke, M, Raychaudhuri, S, Fehrmann, R, Hirschhorn, J, Franke, L, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Ferreira, T, Jackson, A, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, E, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, van der Laan, S, van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De 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Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, van Dijk, S, van Schoor, N, van der Velde, N, van Heemst, D, van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, I, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, de Faire, U, den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, van Duijn, C, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Pers, Th, Karjalainen, Jm, Westra, Hj, Wood, Ar, Lui, Jc, Speliotes, Ek, Hirschhorn, Jn, and Faculty of Health Sciences
Subjects: Cell type, Candidate gene, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, LOCI, General Physics and Astronomy, Genome-wide association study, Disease, Computational biology, Biology, Research Support, General Biochemistry, Genetics and Molecular Biology, Article, DISEASE, N.I.H, CANDIDATE GENES, Genome-Wide Association Study/methods, Software, HEIGHT, Research Support, N.I.H., Extramural, Genetics, Journal Article, NETWORK, Non-U.S. Gov't, Gene, COMMON, Intramural, ARCHITECTURE, Biochemistry, Genetics and Molecular Biology (all), Multidisciplinary, IDENTIFICATION, ta1184, Research Support, Non-U.S. Gov't, Gene sets, Extramural, General Chemistry, ta3121, Research Support, N.I.H., Intramural, Phenotype, 3142 Public health care science, environmental and occupational health, Biological sciences, DATA SETS, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Identification (biology), INTEGRATION, Genome-Wide Association Study
Abstract: Article, The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes., published version, http://purl.org/eprint/status/PeerReviewed
Published: 2015

115. Effectiveness of an electronic patient-centred self-management tool for gout sufferers: A cluster randomised controlled trail protocol

Author: Day, RO, Frensham, LJ, Nguyen, AD, Baysari, MT, Aung, E, Lau, AYS, Zwar, N, Reath, J, Laba, T, Li, L, McLachlan, A, Runciman, WB, Buchbinder, R, Clay-Williams, R, Coiera, E, Braithwaite, J, McNeil, HP, Hunter, DJ, Pile, KJ, Portek, I, Williams, KM, Westbrook, JI, Day, RO, Frensham, LJ, Nguyen, AD, Baysari, MT, Aung, E, Lau, AYS, Zwar, N, Reath, J, Laba, T, Li, L, McLachlan, A, Runciman, WB, Buchbinder, R, Clay-Williams, R, Coiera, E, Braithwaite, J, McNeil, HP, Hunter, DJ, Pile, KJ, Portek, I, Williams, KM, and Westbrook, JI
Abstract: Introduction Gout is increasing despite effective therapies to lower serum urate concentrations to 0.36 mmol/L or less, which, if sustained, significantly reduces acute attacks of gout. Adherence to urate-lowering therapy (ULT) is poor, with rates of less than 50% 1 year after initiation of ULT. Attempts to increase adherence in gout patients have been disappointing. We aim to evaluate the effectiveness of use of a personal, self-management, a'smartphone' application (app) to achieve target serum urate concentrations in people with gout. We hypothesise that personalised feedback of serum urate concentrations will improve adherence to ULT. Methods and analysisSetting and design Primary care. A prospective, cluster randomised (by general practitioner (GP) practices), controlled trial. Participants GP practices will be randomised to either intervention or control clusters with their patients allocated to the same cluster. Intervention The intervention group will have access to the Healthy.me app tailored for the self-management of gout. The control group patients will have access to the same app modified to remove all functions except the Gout Attack Diary. Primary and secondary outcomes The proportion of patients whose serum urate concentrations are less than or equal to 0.36 mmol/L after 6 months. Secondary outcomes will be proportions of patients achieving target urate concentrations at 12 months, ULT adherence rates, serum urate concentrations at 6 and 12 months, rates of attacks of gout, quality of life estimations and process and economic evaluations. The study is designed to detect a ≥30% improvement in the intervention group above the expected 50% achievement of target serum urate at 6 months in the control group: power 0.80, significance level 0.05, assumed a'dropout' rate 20%. Ethics and dissemination This study has been approved by the University of New South Wales Human Research Ethics Committee. Study findings will be disseminated in international conferen
Published: 2017

116. Platelet-Rich Plasma for the Management of Hip and Knee Osteoarthritis

Author: Bennell, KL, Hunter, DJ, Paterson, KL, Bennell, KL, Hunter, DJ, and Paterson, KL
Abstract: PURPOSE OF REVIEW: Knee and hip osteoarthritis (OA) are major public health problems worldwide causing pain, disability and impaired quality of life. This narrative paper discusses platelet-rich plasma (PRP) as a treatment for hip and knee OA, with a focus on evidence from randomised controlled trials (RCTs). RECENT FINDINGS: Since the first RCT of PRP in 2012, there has been 15 RCTs in knee OA and three in hip OA, mostly comparing PRP to another intra-articular injection therapy, hyaluronic acid. All studies are of low to moderate methodological quality and use variable PRP protocols. In general, results showed that PRP is a safe treatment with potential to provide symptomatic benefit for OA at least in the short term (up to 12 months). Younger patients with less severe disease may be more responsive. There are no RCTs investigating the effects of PRP on OA structural changes. No definitive conclusions can be made about the effects of PRP in OA given methodological concerns and considerable heterogeneity between studies. Further high-quality research is needed to establish the clinical and cost-effectiveness of PRP, the patients most likely to benefit and the optimal PRP protocol.
Published: 2017

117. Efficacy of adding a physiotherapy rehabilitation programme to arthroscopic management of femoroacetabular impingement syndrome: a randomised controlled trial (FAIR)

Author: Bennell, KL, Spiers, L, Takla, A, O'Donnell, J, Kasza, J, Hunter, DJ, Hinman, RS, Bennell, KL, Spiers, L, Takla, A, O'Donnell, J, Kasza, J, Hunter, DJ, and Hinman, RS
Abstract: OBJECTIVES: Although several rehabilitation programmes following hip arthroscopy for femoracetabular impingement (FAI) syndrome have been described, there are no clinical trials evaluating whether formal physiotherapy-prescribed rehabilitation improves recovery compared with self-directed rehabilitation. The objective of this study was to evaluate the efficacy of adding a physiotherapist-prescribed rehabilitation programme to arthroscopic surgery for FAI syndrome. DESIGN: Randomised controlled trial. METHODS: People aged ≥16 years with FAI syndrome scheduled for hip arthroscopy were recruited and randomly allocated to physiotherapy (PT) or control. The PT group received seven PT sessions (one preoperative and six postoperative) incorporating education, manual therapy and a progressive rehabilitation programme of home, aquatic and gym exercises while the control group did not undertake PT rehabilitation. Measurements were taken at baseline (2 weeks presurgery) and 14 and 24 weeks postsurgery. The primary outcomes were the International Hip Outcome Tool (iHOT-33) and the sport subscale of the Hip Outcome Score (HOS) at week 14. RESULTS: Due to slower than expected recruitment and funding constraints, recruitment was ceased after 23 months. Thirty participants (14 PT and 16 control) were randomised and 28 (14 PT and 14 control; 93%) and 22 (11 PT and 11 control; 73%) completed week 14 and 24 measurements, respectively. For the 14-week primary outcomes, the PT group showed significantly greater improvements on the iHOT-33 (mean difference 14.2 units; 95% CI 1.2 to 27.2) and sport subscale of the HOS (13.8 units; 95% CI 0.3 to 27.3). There were no significant between-group differences at week 24. CONCLUSIONS: An individual PT treatment and rehabilitation programme may augment improvements in patient-reported outcomes following arthroscopy for FAI syndrome. However, given the small sample size, larger trials are needed to validate the findings. TRIAL REGISTRATION NUMBER
Published: 2017

118. No abatement of steroid injections for tennis elbow in Australian General Practice: A 15-year observational study with random general practitioner sampling

Author: Kumar, S, Vicenzino, B, Britt, H, Pollack, AJ, Hall, M, Bennell, KL, Hunter, DJ, Kumar, S, Vicenzino, B, Britt, H, Pollack, AJ, Hall, M, Bennell, KL, and Hunter, DJ
Abstract: OBJECTIVE: Evaluate general practitioner (GP) management of tennis elbow (TE) in Australia. METHODS: Data about the management of TE by GPs from 2000 to 2015 were extracted from the Bettering the Evaluation of Care of Health program database. Patient and GP characteristics and encounter management data were classified by the International Classification of Primary Care, version 2, and reported using descriptive statistics with point estimates and 95% confidence intervals. RESULTS: TE was managed by GPs 242,000 times per year on average. Patients were mainly female (52.3%), aged between 35 and 64 years (mean: 49.3 yrs), had higher relative risks of concomitant disorders (e.g. carpal tunnel syndrome and other tendonitis) and their TE was 10 times more likely to be work related than problems managed for patients who did not have TE. Use of diagnostic tests was low, implying a clinical examination based diagnosis of TE. Management was by procedural treatments (36 per 100 TE problems), advice, education or counselling (25 per 100), and referral to other health care providers (14 per 100, mainly to physiotherapy). The rate of local injection did not change over the 15 years and was performed at similar rates as physiotherapy referral. CONCLUSION: The high risk of comorbidities and work relatedness and no abatement in the reasonably high rate of local injections (which is contrary to the evidence from clinical trials) provides support for the development and dissemination of TE clinical guidelines for GPs.
Published: 2017

119. Telephone Coaching to Enhance a Home-Based Physical Activity Program for Knee Osteoarthritis: A Randomized Clinical Trial

Author: Bennell, KL, Campbell, PK, Egerton, T, Metcalf, B, Kasza, J, Forbes, A, Bills, C, Gale, J, Harris, A, Kolt, GS, Bunker, SJ, Hunter, DJ, Brand, CA, Hinman, RS, Bennell, KL, Campbell, PK, Egerton, T, Metcalf, B, Kasza, J, Forbes, A, Bills, C, Gale, J, Harris, A, Kolt, GS, Bunker, SJ, Hunter, DJ, Brand, CA, and Hinman, RS
Abstract: OBJECTIVE: To investigate whether simultaneous telephone coaching improves the clinical effectiveness of a physiotherapist-prescribed home-based physical activity program for knee osteoarthritis (OA). METHODS: A total of 168 inactive adults ages ≥50 years with knee pain on a numeric rating scale ≥4 (NRS; range 0-10) and knee OA were recruited from the community and randomly assigned to a physiotherapy (PT) and coaching group (n = 84) or PT-only (n = 84) group. All participants received five 30-minute consultations with a physiotherapist over 6 months for education, home exercise, and physical activity advice. PT+coaching participants also received 6-12 telephone coaching sessions by clinicians trained in behavioral-change support for exercise and physical activity. Primary outcomes were pain (NRS) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC; score range 0-68]) at 6 months. Secondary outcomes were these same measures at 12 and 18 months, as well as physical activity, exercise adherence, other pain and function measures, and quality of life. Analyses were intent-to-treat with multiple imputation for missing data. RESULTS: A total of 142 (85%), 136 (81%), and 128 (76%) participants completed 6-, 12-, and 18-month measurements, respectively. The change in NRS pain (mean difference 0.4 unit [95% confidence interval (95% CI) -0.4, 1.3]) and in WOMAC function (1.8 [95% CI -1.9, 5.5]) did not differ between groups at 6 months, with both groups showing clinically relevant improvements. Some secondary outcomes related to physical activity and exercise behavior favored PT+coaching at 6 months but generally not at 12 or 18 months. There were no between-group differences in most other outcomes. CONCLUSION: The addition of simultaneous telephone coaching did not augment the pain and function benefits of a physiotherapist-prescribed home-based physical activity program.
Published: 2017

120. Protocol for a multi-centre randomised controlled trial comparing arthroscopic hip surgery to physiotherapy-led care for femoroacetabular impingement (FAI): the Australian FASHIoN trial

Author: Murphy, NJ, Eyles, J, Bennell, KL, Bohensky, M, Burns, A, Callaghan, FM, Dickenson, E, Fary, C, Grieve, SM, Griffin, DR, Hall, M, Hobson, R, Kim, YJ, Linklater, JM, Lloyd, DG, Molnar, R, O'Connell, RL, O'Donnell, J, O'Sullivan, M, Randhawa, S, Reichenbach, S, Saxby, DJ, Singh, P, Spiers, L, Phong, T, Wrigley, TV, Hunter, DJ, Murphy, NJ, Eyles, J, Bennell, KL, Bohensky, M, Burns, A, Callaghan, FM, Dickenson, E, Fary, C, Grieve, SM, Griffin, DR, Hall, M, Hobson, R, Kim, YJ, Linklater, JM, Lloyd, DG, Molnar, R, O'Connell, RL, O'Donnell, J, O'Sullivan, M, Randhawa, S, Reichenbach, S, Saxby, DJ, Singh, P, Spiers, L, Phong, T, Wrigley, TV, and Hunter, DJ
Abstract: BACKGROUND: Femoroacetabular impingement syndrome (FAI), a hip disorder affecting active young adults, is believed to be a leading cause of hip osteoarthritis (OA). Current management approaches for FAI include arthroscopic hip surgery and physiotherapy-led non-surgical care; however, there is a paucity of clinical trial evidence comparing these approaches. In particular, it is unknown whether these management approaches modify the future risk of developing hip OA. The primary objective of this randomised controlled trial is to determine if participants with FAI who undergo hip arthroscopy have greater improvements in hip cartilage health, as demonstrated by changes in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to those who undergo physiotherapy-led non-surgical management. METHODS: This is a pragmatic, multi-centre, two-arm superiority randomised controlled trial comparing hip arthroscopy to physiotherapy-led management for FAI. A total of 140 participants with FAI will be recruited from the clinics of participating orthopaedic surgeons, and randomly allocated to receive either surgery or physiotherapy-led non-surgical care. The surgical intervention involves arthroscopic FAI surgery from one of eight orthopaedic surgeons specialising in this field, located in three different Australian cities. The physiotherapy-led non-surgical management is an individualised physiotherapy program, named Personalised Hip Therapy (PHT), developed by a panel to represent the best non-operative care for FAI. It entails at least six individual physiotherapy sessions over 12 weeks, and up to ten sessions over six months, provided by experienced musculoskeletal physiotherapists trained to deliver the PHT program. The primary outcome measure is the change in dGEMRIC score of a ROI containing both acetabular and femoral head cartilages at the chondrolabral transitional zone of the mid-sagittal plane be
Published: 2017

121. Efficacy of combined conservative therapies on clinical outcomes in patients with thumb base osteoarthritis: protocol for a randomised, controlled trial (COMBO)

Author: Deveza, LA, Hunter, DJ, Wajon, A, Bennell, KL, Vicenzino, B, Hodges, P, Eyles, JP, Jongs, R, Riordan, EA, Duong, V, Min Oo, W, O'Connell, R, Meneses, SRF, Deveza, LA, Hunter, DJ, Wajon, A, Bennell, KL, Vicenzino, B, Hodges, P, Eyles, JP, Jongs, R, Riordan, EA, Duong, V, Min Oo, W, O'Connell, R, and Meneses, SRF
Abstract: INTRODUCTION: Management of thumb base osteoarthritis (OA) using a combination of therapies is common in clinical practice; however, evidence for the efficacy of this approach is lacking. The aim of this study is to determine the effect of a combination of conservative therapies for the treatment of thumb base OA compared with an education control group. METHODS AND ANALYSIS: This is a randomised, controlled, single-centre, two-arm superiority trial with 1:1 allocation ratio; with assessor and statistician blinded. Participants are blinded to the trial's hypothesis and to the interventions received by the opposite group. A total of 204 participants will be recruited from the community and randomised using a computer-generated schedule. The intervention group will receive education for joint protection and OA, a splint for the base of the thumb, hand exercises and topical diclofenac sodium 1% gel over 6 weeks. The control group will receive education for joint protection and OA alone. Main inclusion criteria are pain ≥40 mm (Visual Analogue Scale, 0-100) at the base of the thumb, impairment in hand function ≥6 (Functional Index for Hand Osteoarthritis, 0-30) and radiographic thumb base OA (Kellgren Lawrence grade ≥2). Participants currently receiving any of the intervention components will be excluded. Outcomes will be measured at 2, 6 and 12 weeks. The primary outcome is change in pain and hand function from baseline to 6 weeks. Other outcomes include changes in grip and pinch strength, quality of life, presence of joint swelling and tenderness, duration of joint stiffness, patient's global assessment and use of rescue medication. Analysis will be performed according to the intention-to-treat principle. Adverse events will be monitored throughout the study. ETHICS AND DISSEMINATION: This protocol is approved by the local ethics committee (HREC/15/HAWKE/479). Dissemination will occur through presentations at international conferences and publication in peer-reviewed
Published: 2017

122. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, V A, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renstrom, F, Wu, J, Qi, QB, Ahmad, Shahzad, Alfred, T, Amin, Najaf, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Harder, MN, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikainen, LP, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Mueller-Nurasyid, M, Navarro, P, Perusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stancakova, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N (Niek), Vink, JM, Vitart, V, Wu, Fenny, Yengo, L, Zhang, WH, Zhao, JH, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Hottenga, JJ, Huang, J, Hung, J, Hutri-Kahonen, N, Ingelsson, E, James, AL, Jansson, JO, Jarvelin, MR, Jhun, MA, Jorgensen, ME, Juonala, M, Kahonen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Kramer, BK, Kuusisto, J, Kvaloy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Mannikko, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellstrom, D, Menni, C, Montgomery, GW, Musk, AW, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, s, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE (Eline), Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, André, Vandenput, L, Vohl, MC, Volzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, M.C., Baldassarre, D, Balkau, B, Bandinelli, S, Boger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, YDI, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, de Faire, U, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, HJ, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Jukema, W, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimaki, T, Le Marchand, L, Marz, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sorensen, TIA, Strauch, K, Tiemeier, Henning, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, Duijn, Cornelia, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpelainen, TO, Liu, CT, Borecki, IB, North, KE, Cupples, LA, Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, V A, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renstrom, F, Wu, J, Qi, QB, Ahmad, Shahzad, Alfred, T, Amin, Najaf, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Harder, MN, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikainen, LP, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Mueller-Nurasyid, M, Navarro, P, Perusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stancakova, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N (Niek), Vink, JM, Vitart, V, Wu, Fenny, Yengo, L, Zhang, WH, Zhao, JH, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Hottenga, JJ, Huang, J, Hung, J, Hutri-Kahonen, N, Ingelsson, E, James, AL, Jansson, JO, Jarvelin, MR, Jhun, MA, Jorgensen, ME, Juonala, M, Kahonen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Kramer, BK, Kuusisto, J, Kvaloy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Mannikko, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellstrom, D, Menni, C, Montgomery, GW, Musk, AW, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, s, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE (Eline), Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, André, Vandenput, L, Vohl, MC, Volzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, M.C., Baldassarre, D, Balkau, B, Bandinelli, S, Boger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, YDI, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, de Faire, U, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, HJ, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Jukema, W, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimaki, T, Le Marchand, L, Marz, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sorensen, TIA, Strauch, K, Tiemeier, Henning, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, Duijn, Cornelia, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpelainen, TO, Liu, CT, Borecki, IB, North, KE, and Cupples, LA
Published: 2017

123. OARSI recommendations for the management of hip and knee osteoarthritis: part III: Changes in evidence following systematic cumulative update of research published through January 2009

Author: Zhang, W, Nuki, G, Moskowitz, RW, Abramson, S, Altman, RD, Arden, NK, Bierma-Zeinstra, S, Brandt, KD, Croft, P, Doherty, M, Dougados, M, Hochberg, M, Hunter, DJ, Kwoh, K, Lohmander, LS, and Tugwell, P
Abstract: OBJECTIVE: To update evidence for available therapies in the treatment of hip and knee osteoarthritis (OA) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009. METHODS: A systematic literature search was undertaken using MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index and the Cochrane Library. The quality of studies was assessed. Effect sizes (ESs) and numbers needed to treat were calculated for efficacy. Relative risks, hazard ratios (HRs) or odds ratios were estimated for side effects. Publication bias and heterogeneity were examined. Sensitivity analysis was undertaken to compare the evidence pooled in different years and different qualities. Cumulative meta-analysis was used to examine the stability of evidence. RESULTS: Sixty-four systematic reviews, 266 randomised controlled trials (RCTs) and 21 new economic evaluations (EEs) were published between 2006 and 2009. Of 51 treatment modalities, new data on efficacy have been published for more than half (26/39, 67%) of those for which research evidence was available in 2006. Among non-pharmacological therapies, ES for pain relief was unchanged for self-management, education, exercise and acupuncture. However, with new evidence the ES for pain relief for weight reduction reached statistical significance, increasing from 0.13 [95% confidence interval (CI) -0.12, 0.36] in 2006 to 0.20 (95% CI 0.00, 0.39) in 2009. By contrast, the ES for electromagnetic therapy which was large in 2006 (ES=0.77, 95% CI 0.36, 1.17) was no longer significant (ES=0.16, 95% CI -0.08, 0.39). Among pharmacological therapies, the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs, diacerhein and intra-articular (IA) corticosteroid was not greatly changed. The ES for pain relief with acetaminophen diminished numerically, but not significantly, from 0.21 (0.02, 0.41) to 0.14 (0.05, 0.22) and was no longer significant when analysis was restricted to high quality trials (ES=0.10, 95% CI -0.0, 0.23). New evidence for increased risks of hospitalisation due to perforation, peptic ulceration and bleeding with acetaminophen >3g/day have been published (HR=1.20, 95% CI 1.03, 1.40). ES for pain relief from IA hyaluronic acid, glucosamine sulphate, chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias. Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo. CONCLUSION: Publication of a large amount of new research evidence has resulted in changes in the calculated risk-benefit ratio for some treatments for OA. Regular updating of research evidence can help to guide best clinical practice.
Published: 2016

124. Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Author: Gusev, A, Shi, H, Kichaev, G, Pomerantz, M, Li, F, Long, HW, Ingles, SA, Kittles, RA, Strom, SS, Rybicki, BA, Nemesure, B, Isaacs, WB, Zheng, W, Pettaway, CA, Yeboah, ED, Tettey, Y, Biritwum, RB, Adjei, AA, Tay, E, Truelove, A, Niwa, S, Chokkalingam, AP, John, EM, Murphy, AB, Signorello, LB, Carpten, J, Leske, MC, Wu, S-Y, Hennis, AJM, Neslund-Dudas, C, Hsing, AW, Chu, L, Goodman, PJ, Klein, EA, Witte, JS, Casey, G, Kaggwa, S, Cook, MB, Stram, DO, Blot, WJ, Eeles, RA, Easton, D, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Muir, K, Giles, GG, Southey, MC, Fitzgerald, LM, Gronberg, H, Wiklund, F, Aly, M, Henderson, BE, Schleutker, J, Wahlfors, T, Tammela, TLJ, Nordestgaard, BG, Key, TJ, Travis, RC, Neal, DE, Donovan, JL, Hamdy, FC, Pharoah, P, Pashayan, N, Khaw, K-T, Stanford, JL, Thibodeau, SN, McDonnell, SK, Schaid, DJ, Maier, C, Vogel, W, Luedeke, M, Herkommer, K, Kibel, AS, Cybulski, C, Wokolorczyk, D, Kluzniak, W, Cannon-Albright, L, Teerlink, C, Brenner, H, Dieffenbach, AK, Arndt, V, Park, JY, Sellers, TA, Lin, H-Y, Slavov, C, Kaneva, R, Mitev, V, Batra, J, Spurdle, A, Clements, JA, Teixeira, MR, Pandha, H, Michael, A, Paulo, P, Maia, S, Kierzek, A, Conti, DV, Albanes, D, Berg, C, Berndt, SI, Campa, D, Crawford, ED, Diver, WR, Gapstur, SM, Gaziano, JM, Giovannucci, E, Hoover, R, Hunter, DJ, Johansson, M, Kraft, P, Le Marchand, L, Lindstrom, S, Navarro, C, Overvad, K, Riboli, E, Siddiq, A, Stevens, VL, Trichopoulos, D, Vineis, P, Yeager, M, Trynka, G, Raychaudhuri, S, Schumacher, FR, Price, AL, Freedman, ML, Haiman, CA, Pasaniuc, B, Cook, M, Guy, M, Govindasami, K, Leongamornlert, D, Sawyer, EJ, Wilkinson, R, Saunders, EJ, Tymrakiewicz, M, Dadaev, T, Morgan, A, Fisher, C, Hazel, S, Livni, N, Lophatananon, A, Pedersen, J, Hopper, JL, Adolfson, J, Stattin, P, Johansson, J-E, Cavalli-Bjoerkman, C, Karlsson, A, Broms, M, Auvinen, A, Kujala, P, Maeaettaenen, L, Murtola, T, Taari, K, Weischer, M, Nielsen, SF, Klarskov, P, Roder, A, Iversen, P, Wallinder, H, Gustafsson, S, Cox, A, Brown, P, George, A, Marsden, G, Lane, A, Davis, M, Tillmans, L, Riska, S, Wang, L, Rinckleb, A, Lubiski, J, Stegmaier, C, Pow-Sang, J, Park, H, Radlein, S, Rincon, M, Haley, J, Zachariah, B, Kachakova, D, Popov, E, Mitkova, A, Vlahova, A, Dikov, T, Christova, S, Heathcote, P, Wood, G, Malone, G, Saunders, P, Eckert, A, Yeadon, T, Kerr, K, Collins, A, Turner, M, Srinivasan, S, Kedda, M-A, Alexander, K, Omara, T, Wu, H, Henrique, R, Pinto, P, Santos, J, Barros-Silva, J, and Consortium, PRACTICAL
Subjects: urologic and male genital diseases
Abstract: Although genome-wide association studies have identified over 100 risk loci that explain ~33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
Published: 2016

125. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

Author: Bailey, JNC, Loomis, SJ, Kang, JH, Allingham, RR, Gharahkhani, P, Khor, CC, Burdon, KP, Aschard, H, Chasman, DI, Igo, RP, Hysi, PG, Glastonbury, CA, Ashley-Koch, A, Brilliant, M, Brown, AA, Budenz, DL, Buil, A, Cheng, CY, Choi, H, Christen, WG, Curhan, G, De Vivo, I, Fingert, JH, Foster, PJ, Fuchs, C, Gaasterland, D, Gaasterland, T, Hewitt, AW, Hu, F, Hunter, DJ, Khawaja, AP, Lee, RK, Li, Z, Lichter, PR, Mackey, DA, McGuffin, P, Mitchell, P, Moroi, SE, Perera, SA, Pepper, KW, Qi, Q, Realini, T, Richards, JE, Ridker, PM, Rimm, E, Ritch, R, Ritchie, M, Schuman, JS, Scott, WK, Singh, K, Sit, AJ, Song, YE, Tamimi, RM, Topouzis, F, Viswanathan, AC, Verma, SS, Vollrath, D, Wang, JJ, Weisschuh, N, Wissinger, B, Wollstein, G, Wong, TY, Yaspan, BL, Zack, DJ, Zhang, K, Weinreb, RN, Pericak-Vance, MA, Small, K, Hammond, CJ, Aung, T, Liu, Y, Vithana, EN, MacGregor, S, Craig, JE, Kraft, P, Howell, G, Hauser, MA, and Pasquale, LR
Subjects: ANZRAG Consortium
Abstract: © 2016 Nature America, Inc. Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10 -11) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10 -10); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10 -10). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.
Published: 2016

126. Is synovitis detected on non-contrast-enhanced magnetic resonance imaging associated with serum biomarkers and clinical signs of effusion? Data from the Osteoarthritis Initiative

Author: Deveza, LA, primary, Kraus, VB, additional, Collins, JE, additional, Guermazi, A, additional, Roemer, FW, additional, Nevitt, MC, additional, and Hunter, DJ, additional
Published: 2017
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127. OP0171 Signal intensity alteration within infrapatellar fat pad predicts total knee arthroplasty within four years: data from the osteoarthritis initiative

Author: Wang, K, primary, Ding, C, additional, Hannon, MJ, additional, Chen, Z, additional, Kwoh, C, additional, and Hunter, DJ, additional
Published: 2017
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128. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

Author: D. L. Cousminer, D. J. Berry, N. J. Timpson, W. Ang, E. Thiering, E. M. Byrne, H. R. Taal, V. Huikari, J. P. Bradfield, M. Kerkhof, M. M. Groen Blokhuis, E. Kreiner Moller, M. Marinelli, C. Holst, J. T. Leinonen, J. R. B. Perry, I. Surakka, O. Pietilainen, J. Kettunen, V. Anttila, M. Kaakinen, U. Sovio, A. Pouta, S. Das, V. Lagou, C. Power, I. Prokopenko, D. M. Evans, J. P. Kemp, B. St Pourcain, S. Ring, A. Palotie, E. Kajantie, C. Osmond, T. Lehtimaki, J. S. Viikari, M. Kahonen, N. M. Warrington, S. J. Lye, L. J. Palmer, C. M. T. Tiesler, C. Flexeder, G. W. Montgomery, S. E. Medland, A. Hofman, H. Hakonarson, M. Guxens, M. Bartels, V. Salomaa, J. M. Murabito, J. Kaprio, T. I. A. Sorensen, F. Ballester, H. Bisgaard, D. I. Boomsma, G. H. Koppelman, S. F. A. Grant, V. W. V. Jaddoe, N. G. Martin, J. Heinrich, C. E. Pennell, O. T. Raitakari, J. G. Eriksson, G. D. Smith, E. Hypponen, M. R. Jarvelin, M. I. McCarthy, S. Ripatti, E. Widen, Adair LS, Ang W, Atalay M, van Beijsterveldt T, Bergen N, Benke K, Berry DJ, Boomsma DI, Bradfield JP, Charoen P, Coin L, Cooper C, Cousminer DL, Das S, Davis OS, Dedoussis GV, Elliott P, Estivill X, Evans DM, Feenstra B, Flexeder C, Frayling T, Freathy RM, Gaillard R, Geller F, Gillman M, Grant SF, Groen Blokhuis M, Goh LK, Guxens M, Hakonarson H, Hattersley AT, Haworth CM, Hadley D, Hedebrand J, Heinrich J, Hinney A, Hirschhorn JN, Hocher B, Holloway JW, Holst C, Hottenga JJ, Horikoshi M, Huikari V, Hypponen E, Iñiguez C, Jaddoe VW, Jarvelin MR, Kaakinen M, Kilpeläinen TO, Kirin M, Kowgier M, Lakka HM, Lakka TA, Lange LA, Lawlor DA, Lehtimäki T, Lewin A, Lindgren C, Lindi V, Maggi R, Marsh J, McCarthy MI, Melbye M, Middeldorp C, Millwood I, Mohlke KL, Mook Kanamori DO, Murray JC, Nivard M, Nohr EA, Ntalla I, Oken E, Ong KK, O'Reilly PF, Palmer LJ, Panoutsopoulou K, Pararajasingham J, Pearson ER, Pennell CE, Power C, Price TS, Prokopenko I, Raitakari OT, Rodriguez A, Salem RM, Saw SM, Scherag A, Sebert S, Siitonen N, Simell O, Sørensen TI, Sovio U, Pourcain BS, Strachan DP, Sunyer J, Taal HR, Teo YY, Thiering E, Tiesler C, Timpson NJ, Uitterlinden AG, Valcárcel B, Warrington NM, White S, Widén E, Willemsen G, Wilson JF, Yaghootkar H, Zeggini E, Elks CE, Perry JR, Sulem P, Chasman DI, Franceschini N, He C, Lunetta KL, Visser JA, Byrne EM, Gudbjartsson DF, Esko T, Koller DL, Kutalik Z, Lin P, Mangino M, Marongiu M, McArdle PF, Smith AV, Stolk L, van Wingerden SH, Zhao JH, Albrecht E, Corre T, Ingelsson E, Hayward C, Magnusson PK, Smith EN, Ulivi S, Warrington M, Zgaga L, Alavere H, Amin N, Aspelund T, Bandinelli S, Barroso I, Berenson GS, Bergmann S, Blackburn H, Boerwinkle E, Buring JE, Busonero F, Campbell H, Chanock SJ, Chen W, Cornelis MC, Couper D, Coviello AD, de Faire U, de Geus EJ, Deloukas P, Döring A, Davey Smith G, Easton DF, Eiriksdottir G, Emilsson V, Eriksson J, Ferrucci L, Folsom AR, Foroud T, Garcia M, GASPARINI, PAOLO, Gieger C, Gudnason V, Hall P, Hankinson SE, Ferreli L, Heath AC, Hernandez DG, Hofman A, Hu FB, Illig T, Järvelin MR, Johnson AD, Karasik D, Khaw KT, Kiel DP, Kolcic I, Kraft P, Launer LJ, Laven JS, Li S, Liu J, Levy D, Martin NG, McArdle WL, Mooser V, Murray SS, Nalls MA, Navarro P, Nelis M, Ness AR, Northstone K, Oostra BA, Peacock M, Palotie A, Paré G, Parker AN, Pedersen NL, Peltonen L, Pharoah P, Polasek O, Plump AS, Pouta A, Porcu E, Rafnar T, Rice JP, Ring SM, Rivadeneira F, Rudan I, Sala C, Salomaa V, Sanna S, Schlessinger D, Schork NJ, Scuteri A, Segrè AV, Shuldiner AR, Soranzo N, Srinivasan SR, Tammesoo ML, Tikkanen E, Toniolo D, Tsui K, Tryggvadottir L, Tyrer J, Uda M, van Dam RM, van Meurs JB, Vollenweider P, Waeber G, Wareham NJ, Waterworth DM, Weedon MN, Wichmann HE, Wright AF, Young L, Zhai G, Zhuang WV, Bierut LJ, Boyd HA, Crisponi L, Demerath EW, van Duijn CM, Econs MJ, Harris TB, Hunter DJ, Loos RJ, Metspalu A, Montgomery GW, Ridker PM, Spector TD, Streeten EA, Stefansson K, Thorsteinsdottir U, Widen E, Murabito JM, Murray A., D'ADAMO, ADAMO PIO, Cousminer, Diana L, Berry, Diane J, Timpson, Nicholas J, Ang, Wei, Hyppönen, Elina, Widen, Elisabéth, ReproGen Consortium, Early Growth Genetics (EGG) Consortium, Pediatrics, Epidemiology, Internal Medicine, D. L., Cousminer, D. J., Berry, N. J., Timpson, W., Ang, E., Thiering, E. M., Byrne, H. R., Taal, V., Huikari, J. P., Bradfield, M., Kerkhof, M. M., Groen Blokhui, E., Kreiner Moller, M., Marinelli, C., Holst, J. T., Leinonen, J. R. B., Perry, I., Surakka, O., Pietilainen, J., Kettunen, V., Anttila, M., Kaakinen, U., Sovio, A., Pouta, S., Da, V., Lagou, C., Power, I., Prokopenko, D. M., Evan, J. P., Kemp, B., St Pourcain, S., Ring, A., Palotie, E., Kajantie, C., Osmond, T., Lehtimaki, J. S., Viikari, M., Kahonen, N. M., Warrington, S. J., Lye, L. J., Palmer, C. M. T., Tiesler, C., Flexeder, G. W., Montgomery, S. E., Medland, A., Hofman, H., Hakonarson, M., Guxen, M., Bartel, V., Salomaa, J. M., Murabito, J., Kaprio, T. I. A., Sorensen, F., Ballester, H., Bisgaard, D. I., Boomsma, G. H., Koppelman, S. F. A., Grant, V. W. V., Jaddoe, N. G., Martin, J., Heinrich, C. E., Pennell, O. T., Raitakari, J. G., Eriksson, G. D., Smith, E., Hypponen, M. R., Jarvelin, M. I., Mccarthy, S., Ripatti, E., Widen, Adair, L, Ang, W, Atalay, M, van Beijsterveldt, T, Bergen, N, Benke, K, Berry, Dj, Boomsma, Di, Bradfield, Jp, Charoen, P, Coin, L, Cooper, C, Cousminer, Dl, Das, S, Davis, O, Dedoussis, Gv, Elliott, P, Estivill, X, Evans, Dm, Feenstra, B, Flexeder, C, Frayling, T, Freathy, Rm, Gaillard, R, Geller, F, Gillman, M, Grant, Sf, Groen Blokhuis, M, Goh, Lk, Guxens, M, Hakonarson, H, Hattersley, At, Haworth, Cm, Hadley, D, Hedebrand, J, Heinrich, J, Hinney, A, Hirschhorn, Jn, Hocher, B, Holloway, Jw, Holst, C, Hottenga, Jj, Horikoshi, M, Huikari, V, Hypponen, E, Iñiguez, C, Jaddoe, Vw, Jarvelin, Mr, Kaakinen, M, Kilpeläinen, To, Kirin, M, Kowgier, M, Lakka, Hm, Lakka, Ta, Lange, La, Lawlor, Da, Lehtimäki, T, Lewin, A, Lindgren, C, Lindi, V, Maggi, R, Marsh, J, Mccarthy, Mi, Melbye, M, Middeldorp, C, Millwood, I, Mohlke, Kl, Mook Kanamori, Do, Murray, Jc, Nivard, M, Nohr, Ea, Ntalla, I, Oken, E, Ong, Kk, O'Reilly, Pf, Palmer, Lj, Panoutsopoulou, K, Pararajasingham, J, Pearson, Er, Pennell, Ce, Power, C, Price, T, Prokopenko, I, Raitakari, Ot, Rodriguez, A, Salem, Rm, Saw, Sm, Scherag, A, Sebert, S, Siitonen, N, Simell, O, Sørensen, Ti, Sovio, U, Pourcain, B, Strachan, Dp, Sunyer, J, Taal, Hr, Teo, Yy, Thiering, E, Tiesler, C, Timpson, Nj, Uitterlinden, Ag, Valcárcel, B, Warrington, Nm, White, S, Widén, E, Willemsen, G, Wilson, Jf, Yaghootkar, H, Zeggini, E, Elks, Ce, Perry, Jr, Sulem, P, Chasman, Di, Franceschini, N, He, C, Lunetta, Kl, Visser, Ja, Byrne, Em, Gudbjartsson, Df, Esko, T, Koller, Dl, Kutalik, Z, Lin, P, Mangino, M, Marongiu, M, Mcardle, Pf, Smith, Av, Stolk, L, van Wingerden, Sh, Zhao, Jh, Albrecht, E, Corre, T, Ingelsson, E, Hayward, C, Magnusson, Pk, Smith, En, Ulivi, S, Warrington, M, Zgaga, L, Alavere, H, Amin, N, Aspelund, T, Bandinelli, S, Barroso, I, Berenson, G, Bergmann, S, Blackburn, H, Boerwinkle, E, Buring, Je, Busonero, F, Campbell, H, Chanock, Sj, Chen, W, Cornelis, Mc, Couper, D, Coviello, Ad, D'Adamo, ADAMO PIO, de Faire, U, de Geus, Ej, Deloukas, P, Döring, A, Davey Smith, G, Easton, Df, Eiriksdottir, G, Emilsson, V, Eriksson, J, Ferrucci, L, Folsom, Ar, Foroud, T, Garcia, M, Gasparini, Paolo, Gieger, C, Gudnason, V, Hall, P, Hankinson, Se, Ferreli, L, Heath, Ac, Hernandez, Dg, Hofman, A, Hu, Fb, Illig, T, Järvelin, Mr, Johnson, Ad, Karasik, D, Khaw, Kt, Kiel, Dp, Kolcic, I, Kraft, P, Launer, Lj, Laven, J, Li, S, Liu, J, Levy, D, Martin, Ng, Mcardle, Wl, Mooser, V, Murray, S, Nalls, Ma, Navarro, P, Nelis, M, Ness, Ar, Northstone, K, Oostra, Ba, Peacock, M, Palotie, A, Paré, G, Parker, An, Pedersen, Nl, Peltonen, L, Pharoah, P, Polasek, O, Plump, A, Pouta, A, Porcu, E, Rafnar, T, Rice, Jp, Ring, Sm, Rivadeneira, F, Rudan, I, Sala, C, Salomaa, V, Sanna, S, Schlessinger, D, Schork, Nj, Scuteri, A, Segrè, Av, Shuldiner, Ar, Soranzo, N, Srinivasan, Sr, Tammesoo, Ml, Tikkanen, E, Toniolo, D, Tsui, K, Tryggvadottir, L, Tyrer, J, Uda, M, van Dam, Rm, van Meurs, Jb, Vollenweider, P, Waeber, G, Wareham, Nj, Waterworth, Dm, Weedon, Mn, Wichmann, He, Wright, Af, Young, L, Zhai, G, Zhuang, Wv, Bierut, Lj, Boyd, Ha, Crisponi, L, Demerath, Ew, van Duijn, Cm, Econs, Mj, Harris, Tb, Hunter, Dj, Loos, Rj, Metspalu, A, Montgomery, Gw, Ridker, Pm, Spector, Td, Streeten, Ea, Stefansson, K, Thorsteinsdottir, U, Widen, E, Murabito, Jm, Murray, A., Hedebrand, Johannes (Beitragende*r), Hinney, Anke (Beitragende*r), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Faculteit Medische Wetenschappen/UMCG, Groningen Research Institute of Pharmacy, and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: Male, Netherlands Twin Register (NTR), Genetic Linkage, Medizin, Gene Expression, Genome-wide association study, VARIANTS, Body Mass Index, 0302 clinical medicine, genetic linkage, Transforming Growth Factor beta, Neoplasms, molecular biology, genetics, Child, Genetics (clinical), Adiposity, 2. Zero hunger, 0303 health sciences, adiposity, Mitogen-Activated Protein Kinase 3, Association Studies Articles, Age Factors, ACHONDROPLASIA, General Medicine, Genome-Wide Association Study, pubertal height growth, pubertal timing, Phenotype, OBESITY, Menarche, body height, Female, Signal Transduction, medicine.medical_specialty, age factors, CHROMOSOME 16P11.2, Adolescent, BIRTH, Quantitative Trait Loci, 030209 endocrinology & metabolism, Context (language use), Biology, Childhood obesity, MENARCHE, Young Adult, 03 medical and health sciences, AGE, SDG 3 - Good Health and Well-being, Prepuberty, Internal medicine, Genetics, medicine, Humans, Molecular Biology, 030304 developmental biology, Sign, FACTOR RECEPTOR-3, MUTATIONS, Puberty, ta3121, medicine.disease, Obesity, Body Height, Genetic architecture, Endocrinology, POPULATION COHORT, gene expression, Body mass index, Follow-Up Studies
Abstract: The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P
Published: 2013

129. Two susceptibility loci identified for prostate cancer aggressiveness

Author: Berndt, Si, Wang, Z, Yeager, M, Alavanja, Mc, Albanes, D, Amundadottir, L, Andriole, G, Beane Freeman, L, Campa, D, Cancel-Tassin, G, Canzian, F, Cornu, Jn, Cussenot, O, Diver, Wr, Gapstur, Sm, Grönberg, H, Haiman, Ca, Henderson, B, Hutchinson, A, Hunter, Dj, Key, Tj, Kolb, S, Koutros, S, Kraft, P, Le Marchand, L, Lindström, S, Machiela, Mj, Ostrander, Ea, Riboli, E, Schumacher, F, Siddiq, A, Stanford, Jl, Stevens, Vl, Travis, Rc, Tsilidis, Kk, Virtamo, J, Weinstein, S, Wilkund, F, Xu, J, Lilly Zheng, S, Yu, K, Wheeler, W, Zhang, H, African, Ancestry Prostate Cancer GWAS Consortium, Sampson, J, Black, A, Jacobs, K, Hoover, Rn, Tucker, M, Chanock, Sj. Ingles SA, Kittles, Ra, Strom, Ss, Rybicki, Ba, Nemesure, B, Isaacs, Wb, Zheng, W, Pettaway, Ca, Yeboah, Ed, Tettey, Y, Biritwum, Rb, Adjei, Aa, Tay, E, Truelove, A, Niwa, S, Chokkalingam, Ap, John, Em, Murphy, Ab, Signorello, Lb, Carpten, J, Leske, Mc, Wu, Sy, Hennis, Aj, Neslund-Dudas, C, Hsing, Aw, Chu, L, Goodman, Pj, Klein, Ea, Witte, Js, Casey, G, Kaggwa, S, Cook, Mb, Stram, Do, and Blot, Wj.
Subjects: Oncology, Male, Aging, GLEASON SCORE, LINKAGE SCAN, General Physics and Astronomy, Genome-wide association study, Disease, Bioinformatics, Prostate cancer, SEQUENCE VARIANTS, Medicine, 2.1 Biological and endogenous factors, GTPASE-ACTIVATING PROTEIN, Aetiology, POPULATION, Cancer, RISK, education.field_of_study, African Ancestry Prostate Cancer GWAS Consortium, Multidisciplinary, Prostate Cancer, 3. Good health, Multidisciplinary Sciences, Science & Technology - Other Topics, Urologic Diseases, medicine.medical_specialty, Population, Article, General Biochemistry, Genetics and Molecular Biology, GENOME-WIDE ASSOCIATION, BASE-LINE CHARACTERISTICS, COHORT, METAANALYSIS, Internal medicine, Genetics, SNP, Humans, Neoplasm Invasiveness, Genetic Predisposition to Disease, education, Pathological, Science & Technology, business.industry, Vascular disease, Prevention, Human Genome, Case-control study, Prostatic Neoplasms, General Chemistry, medicine.disease, Genetic Loci, Case-Control Studies, Neoplasm Grading, business
Abstract: Most men diagnosed with prostate cancer will experience indolent disease; hence, discovering genetic variants that distinguish aggressive from nonaggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49 × 10(-9)) and rs78943174 at 3q26.31 (NAALADL2, P=4.18 × 10(-8)). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85 × 10(-5)) with no association for nonaggressive prostate cancer compared with controls (P=0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation.
Published: 2015

130. Large-Scale Genomic Analyses Link Reproductive Aging to Hypothalamic Signaling, Breast Cancer Susceptibility, and BRCA1-Mediated DNA Repair EDITORIAL COMMENT

Author: Day, FR, Ruth, KS, Thompson, DJ, Lunetta, KL, Pervjakova, N, Chasman, DI, Stolk, Lisette, Finucane, HK, Sulem, P, Bulik-Sullivan, B, Esko, T, Johnson, AD, Elks, CE, Franceschini, N, He, C, Altmaier, E, Brody, JA, Franke, LL, Huffman, JE, Keller, MF, McArdle, PF, Nutile, T, Porcu, E, Robino, A, Rose, LM, Schick, UM, Smith, JA, Teumer, A, Traglia, M, Vuckovic, D, Yao, J, Zhao, W, Albrecht, E, Amin, Najaf, Corre, T, Hottenga, JJ (Jouke Jan), Mangino, M, Smith, AV, Tanaka, T, Abecasis, GR, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Arndt, V, Arnold, AM, Barbieri, C, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bernstein, L, Bielinski, SJ, Blomqvist, C, Boerwinkle, E, Bogdanova, NV, Bojesen, SE, Bolla, MK, Borresen-Dale, AL, Boutin, TS, Brauch, H, Brenner, H, Bruning, T, Burwinkel, B, Campbell, A (Archie), Campbell, H, Chanock, SJ, Chapman, JR, Chen, YDI, Chenevix-Trench, G, Couch, FJ, Coviello, AD, Cox, A, Czene, K, Darabi, H, de Vivo, I, Demerath, EW, Dennis, J, Devilee, P, Dork, T, dos-Santos-Silva, I, Dunning, AM, Eicher, JD, Fasching, PA, Faul, JD, Figueroa, J, Flesch-Janys, D, Gandin, I, Garcia, ME, Garcia-Closas, M, Giles, GG, Girotto, GG, Goldberg, MS, Gonzalez-Neira, A, Goodarzi, MO, Grove, ML, Gudbjartsson, DF, Guenel, P, Guo, XQ, Haiman, CA, Hall, P, Hamann, U, Henderson, BE, Hocking, LJ, Hofman, Bert, Homuth, G, Hooning, Maartje, Hopper, JL, Hu, FB, Huang, JY, Humphreys, K, Hunter, DJ, Jakubowska, A, Jones, SE, Kabisch, M, Karasik, D, Knight, JA, Kolcic, I, Kooperberg, C, Kosma, VM, Kriebel, J, Kristensen, V, Lambrechts, D, Langenberg, C, Li, JM, Li, X, Lindstrom, S, Liu, YM, Luan, JA, Lubinski, J, Magi, R, Mannermaa, A, Manz, J, Margolin, S, Marten, J, Martin, NG, Masciullo, C, Meindl, A, Michailidou, K, Mihailov, E, Milani, L, Milne, RL, Muller-Nurasyid, M, Nalls, M, Neale, BM, Nevanlinna, H, Neven, P, Newman, AB, Nordestgaard, BG, Olson, JE, Padmanabhan, S, Peterlongo, P, Peters, U, Petersmann, A, Peto, J, Pharoah, PDP, Pirastu, NN, Pirie, A, Pistis, G, Polasek, O, Porteous, D, Psaty, BM, Pylkas, K, Radice, P, Raffel, LJ, Rivadeneira, Fernando, Rudan, I, Rudolph, A, Ruggiero, D, Sala, CF, Sanna, S, Sawyer, EJ, Schlessinger, D, Schmidt, MK (Marjanka), Schmidt, F, Schmutzler, RK, Schoemaker, MJ, Scott, RA, Seynaeve, Caroline, Simard, J, Sorice, R, Southey, MC, Stockl, D, Strauch, K, Swerdlow, A, Taylor, KD, Thorsteinsdottir, U, Toland, AE, Tomlinson, I, Truong, T, Tryggvadottir, L, Turner, ST, Vozzi, D, Wang, Q (Qing), Wellons, M, Willemsen, G, Wilson, JF, Winqvist, R, Wolffenbuttel, BBHR, Wright, AF, Yannoukakos, D, Zemunik, T, Zheng, W, Zygmunt, M, Bergmann, S, Boomsma, DI, Buring, JE, Ferrucci, L, Montgomery, GW, Gudnason, V, Spector, TD, Duijn, Cornelia, Alizadeh, BZ, Ciullo, M, Crisponi, L, Easton, DF, Gasparini, PP, Gieger, C, Harris, TB, Hayward, C, Kardia, SLR, Kraft, P, McKnight, B, Metspalu, A, Morrison, AC, Reiner, AP, Ridker, PM, Rotter, JI, Toniolo, D, Uitterlinden, André, Ulivi, S, Volzke, H, Wareham, NJ, Weir, DR, Yerges-Armstrong, LM, Price, AL, Stefansson, K, Visser, Jenny, Ong, KK, Chang-Claude, J, Murabito, JM, Perry, JRB, Murray, A, Systems Ecology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Internal Medicine, Epidemiology, Medical Oncology, and Clinical Genetics
Subjects: SDG 3 - Good Health and Well-being
Published: 2015

131. Identification of novel genetic markers of breast cancer survival

Author: Guo, Q, Schmidt, Mk, Kraft, P, Canisius, S, Chen, C, Khan, S, Tyrer, J, Bolla, Mk, Wang, Q, Dennis, J, Michailidou, K, Lush, M, Kar, S, Beesley, J, Dunning, Am, Shah, M, Czene, K, Darabi, H, Eriksson, M, Lambrechts, D, Weltens, C, Leunen, K, Bojesen, Se, Nordestgaard, Bg, Nielsen, Sf, Flyger, H, Chang Claude, J, Rudolph, A, Seibold, P, Flesch Janys, D, Blomqvist, C, Aittomäki, K, Fagerholm, R, Muranen, Ta, Couch, Fj, Olson, Je, Vachon, C, Andrulis, Il, Knight, Ja, Glendon, G, Mulligan, Am, Broeks, A, Hogervorst, Fb, Haiman, Ca, Henderson, Be, Schumacher, F, Le Marchand, L, Hopper, Jl, Tsimiklis, H, Apicella, C, Southey, Mc, Cox, A, Cross, Ss, Reed, Mw, Giles, Gg, Milne, Rl, Mclean, C, Winqvist, R, Pylkäs, K, Jukkola Vuorinen, A, Grip, M, Hooning, Mj, Hollestelle, A, Martens, Jw, van den Ouweland, Am, Marme, F, Schneeweiss, A, Yang, R, Burwinkel, B, Figueroa, J, Chanock, Sj, Lissowska, J, Sawyer, Ej, Tomlinson, I, Kerin, Mj, Miller, N, Brenner, H, Dieffenbach, Ak, Arndt, V, Holleczek, B, Mannermaa, A, Kataja, V, Kosma, Vm, Hartikainen, Jm, Li, J, Brand, Js, Humphreys, K, Devilee, P, Tollenaar, Ra, Seynaeve, C, Radice, P, Peterlongo, P, Bonanni, B, Mariani, P, Fasching, Beckmann, Mw, Hein, A, Ekici, Ab, Chenevix Trench, G, Balleine, R, Kconfab, Investigators, Phillips, Ka, Benitez, J, Zamora, Mp, Arias Perez, Ji, Menéndez, P, Jakubowska, A, Lubinski, J, Jaworska Bieniek, K, Durda, K, Hamann, U, Kabisch, M, Ulmer, Hu, Rüdiger, T, Margolin, S, Kristensen, V, Nord, S, Evans, Dg, Abraham, Je, Earl, Hm, Hiller, L, Dunn, Ja, Bowden, S, Berg, C, Campa, Daniele, Diver, Wr, Gapstur, Sm, Gaudet, Mm, Hankinson, Se, Hoover, Rn, Hüsing, A, Kaaks, R, Machiela, Mj, Willett, W, Barrdahl, M, Canzian, F, Chin, Sf, Caldas, C, Hunter, Dj, Lindstrom, S, García Closas, M, Hall, P, Easton, Df, Eccles, Dm, Rahman, N, Nevanlinna, H, and Pharoah, P. d.
Subjects: GENOME-WIDE ASSOCIATION, SINGLE-NUCLEOTIDE POLYMORPHISMS, GENOTYPE IMPUTATION, PROGNOSIS, RISK, LOCI, CYCLOPHOSPHAMIDE, METAANALYSIS, PROGRESSION, EPIRUBICIN
Published: 2015

132. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author: Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, EJ, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, CC, Hautman, C, Arslan, AA, Beane-Freeman, L, Bracci, PM, Buring, J, Duell, EJ, Gallinger, S, Giles, GG, Goodman, GE, Goodman, PJ, Kamineni, A, Kolonel, LN, Kulke, MH, Malats, N, Olson, SH, Sesso, HD, Visvanathan, K, White, E, Zheng, W, Abnet, CC, Albanes, D, Andreotti, G, Brais, L, Bueno-de-Mesquita, HB, Basso, D, Berndt, SI, Boutron-Ruault, M-C, Bijlsma, MF, Brenner, H, Burdette, L, Campa, D, Caporaso, NE, Capurso, G, Cavestro, GM, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, JM, Gazouli, M, Giovannucci, EL, Goggins, M, Gross, M, Haiman, CA, Hassan, M, Helzlsouer, KJ, Hu, N, Hunter, DJ, Iskierka-Jazdzewska, E, Jenab, M, Kaaks, R, Key, TJ, Khaw, K-T, Klein, EA, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, RC, Landi, MT, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, RL, Neale, RE, Oberg, AL, Panico, S, Patel, AV, Peeters, PHM, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Ramon Quiros, J, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, X-O, Silverman, DT, Soucek, P, Strobel, O, Sund, M, Malecka-Panas, E, Taylor, PR, Tavano, F, Travis, RC, Thornquist, M, Tjonneland, A, Tobias, GS, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski-Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Kooperberg, C, Risch, HA, Jacobs, EJ, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, SJ, Petersen, GM, Stolzenberg-Solomon, RS, Wolpin, BM, Kraft, P, Klein, AP, Canzian, F, Amundadottir, LT, Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, EJ, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, CC, Hautman, C, Arslan, AA, Beane-Freeman, L, Bracci, PM, Buring, J, Duell, EJ, Gallinger, S, Giles, GG, Goodman, GE, Goodman, PJ, Kamineni, A, Kolonel, LN, Kulke, MH, Malats, N, Olson, SH, Sesso, HD, Visvanathan, K, White, E, Zheng, W, Abnet, CC, Albanes, D, Andreotti, G, Brais, L, Bueno-de-Mesquita, HB, Basso, D, Berndt, SI, Boutron-Ruault, M-C, Bijlsma, MF, Brenner, H, Burdette, L, Campa, D, Caporaso, NE, Capurso, G, Cavestro, GM, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, JM, Gazouli, M, Giovannucci, EL, Goggins, M, Gross, M, Haiman, CA, Hassan, M, Helzlsouer, KJ, Hu, N, Hunter, DJ, Iskierka-Jazdzewska, E, Jenab, M, Kaaks, R, Key, TJ, Khaw, K-T, Klein, EA, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, RC, Landi, MT, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, RL, Neale, RE, Oberg, AL, Panico, S, Patel, AV, Peeters, PHM, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Ramon Quiros, J, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, X-O, Silverman, DT, Soucek, P, Strobel, O, Sund, M, Malecka-Panas, E, Taylor, PR, Tavano, F, Travis, RC, Thornquist, M, Tjonneland, A, Tobias, GS, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski-Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Kooperberg, C, Risch, HA, Jacobs, EJ, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, SJ, Petersen, GM, Stolzenberg-Solomon, RS, Wolpin, BM, Kraft, P, Klein, AP, Canzian, F, and Amundadottir, LT
Abstract: Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
Published: 2016

133. The influence of weather on the risk of pain exacerbation in patients with knee osteoarthritis - a case-crossover study

Author: Ferreira, ML, Zhang, Y, Metcalf, B, Makovey, J, Bennell, KL, March, L, Hunter, DJ, Ferreira, ML, Zhang, Y, Metcalf, B, Makovey, J, Bennell, KL, March, L, and Hunter, DJ
Abstract: OBJECTIVE: To quantify the risk of knee pain exacerbation associated with temperature, relative humidity, air pressure and precipitation in persons with knee osteoarthritis. METHOD: A web-based case-crossover study was conducted. Participants with a diagnosis of symptomatic, radiographic knee osteoarthritis were measured at baseline and followed for 3 months. Participants were instructed to log on to the study website if they perceived experiencing knee pain exacerbation (hazard period). Pain exacerbation was defined as an increase of ≥2 on a 0-10 numeric rating scale (NRS) from the participant's mildest pain reported at baseline. A time-stratified case-crossover study was conducted to anchor the corresponding hazard date to four control periods within a particular 35-day interval. Data on maximum and minimum temperature (°C), relative humidity (%), barometric pressure (hPa) and precipitation (mm) were obtained for the hazard and control periods from the publicly available meteorological database of the Australian Bureau of Meteorology. The associations were assessed using conditional logistic regression. RESULTS: Of the 345 participants recruited, 171 participants (women: 64%, mean age: 62 years, mean BMI: 30.2 kg/m2) experienced at least one episode of pain exacerbation, yielding 1,425 observations included in the analyses. There was no apparent association between temperature, relative humidity, air pressure or precipitation and risk of knee pain exacerbation. CONCLUSION: Despite anecdotal reports from patients, change in weather factors does not appear to influence the risk of pain exacerbation in persons with knee osteoarthritis. Additional studies should quantify the association of weather and risk of pain exacerbation in regions with more extreme weather conditions.
Published: 2016

134. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Author: Couch, FJ, Kuchenbaecker, KB, Michailidou, K, Mendoza-Fandino, GA, Nord, S, Lilyquist, J, Olswold, C, Hallberg, E, Agata, S, Ahsan, H, Aittomaeki, K, Ambrosone, C, Andrulis, IL, Anton-Culver, H, Arndt, V, Arun, BK, Arver, B, Barile, M, Barkardottir, RB, Barrowdale, D, Beckmann, L, Beckmann, MW, Benitez, J, Blank, SV, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Canzian, F, Carpenter, J, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Damiola, F, Darabi, H, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, dos-Santos-Silva, I, Dumont, M, Dunning, AM, Eccles, DM, Ehrencrona, H, Ekici, AB, Eliassen, H, Ellis, S, Fasching, PA, Figueroa, J, Flesch-Janys, D, Foersti, A, Fostira, F, Foulkes, WD, Friebel, T, Friedman, E, Frost, D, Gabrielson, M, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Gaudet, MM, Gayther, SA, Gerdes, A-M, Ghoussaini, M, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Gronwald, J, Guenel, P, Gunter, M, Haeberle, L, Haiman, CA, Hamann, U, Hansen, TVO, Hart, S, Healey, S, Heikkinen, T, Henderson, BE, Herzog, J, Hogervorst, FBL, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Humphreys, K, Hunter, DJ, Huzarski, T, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Jones, M, Kabisch, M, Kar, S, Karlan, BY, Khan, S, Khaw, K-T, Kibriya, MG, Knight, JA, Ko, Y-D, Konstantopoulou, I, Kosma, V-M, Kristensen, V, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C, Lee, E, Le Marchand, L, Lester, J, Lindblom, A, Lindor, N, Lindstrom, S, Liu, J, Long, J, Lubinski, J, Mai, PL, Makalic, E, Malone, KE, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Martens, JWM, McGuffog, L, Meindl, A, Miller, A, Milne, RL, Miron, P, Montagna, M, Mazoyer, S, Mulligan, AM, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olson, JE, Osorio, A, Park, SK, Peeters, PH, Peissel, B, Peterlongo, P, Peto, J, Phelan, CM, Pilarski, R, Poppe, B, Pylkaes, K, Radice, P, Rahman, N, Rantala, J, Rappaport, C, Rennert, G, Richardson, A, Robson, M, Romieu, I, Rudolph, A, Rutgers, EJ, Sanchez, M-J, Santella, RM, Sawyer, EJ, Schmidt, DF, Schmidt, MK, Schmutzler, RK, Schumacher, F, Scott, R, Senter, L, Sharma, P, Simard, J, Singer, CF, Sinilnikova, OM, Soucy, P, Southey, M, Steinemann, D, Stenmark-Askmalm, M, Stoppa-Lyonnet, D, Swerdlow, A, Szabo, CI, Tamimi, R, Tapper, W, Teixeira, MR, Teo, S-H, Terry, MB, Thomassen, M, Thompson, D, Tihomirova, L, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tsimiklis, H, Teule, A, Tumino, R, Tung, N, Turnbull, C, Ursin, G, van Deurzen, CHM, van Rensburg, EJ, Varon-Mateeva, R, Wang, Z, Wang-Gohrke, S, Weiderpass, E, Weitzel, JN, Whittemore, A, Wildiers, H, Winqvist, R, Yang, XR, Yannoukakos, D, Yao, S, Zamora, MP, Zheng, W, Hall, P, Kraft, P, Vachon, C, Slager, S, Chenevix-Trench, G, Pharoah, PDP, Monteiro, AAN, Garcia-Closas, M, Easton, DF, Antoniou, AC, Couch, FJ, Kuchenbaecker, KB, Michailidou, K, Mendoza-Fandino, GA, Nord, S, Lilyquist, J, Olswold, C, Hallberg, E, Agata, S, Ahsan, H, Aittomaeki, K, Ambrosone, C, Andrulis, IL, Anton-Culver, H, Arndt, V, Arun, BK, Arver, B, Barile, M, Barkardottir, RB, Barrowdale, D, Beckmann, L, Beckmann, MW, Benitez, J, Blank, SV, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Canzian, F, Carpenter, J, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Damiola, F, Darabi, H, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, dos-Santos-Silva, I, Dumont, M, Dunning, AM, Eccles, DM, Ehrencrona, H, Ekici, AB, Eliassen, H, Ellis, S, Fasching, PA, Figueroa, J, Flesch-Janys, D, Foersti, A, Fostira, F, Foulkes, WD, Friebel, T, Friedman, E, Frost, D, Gabrielson, M, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Gaudet, MM, Gayther, SA, Gerdes, A-M, Ghoussaini, M, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Gronwald, J, Guenel, P, Gunter, M, Haeberle, L, Haiman, CA, Hamann, U, Hansen, TVO, Hart, S, Healey, S, Heikkinen, T, Henderson, BE, Herzog, J, Hogervorst, FBL, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Humphreys, K, Hunter, DJ, Huzarski, T, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Jones, M, Kabisch, M, Kar, S, Karlan, BY, Khan, S, Khaw, K-T, Kibriya, MG, Knight, JA, Ko, Y-D, Konstantopoulou, I, Kosma, V-M, Kristensen, V, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C, Lee, E, Le Marchand, L, Lester, J, Lindblom, A, Lindor, N, Lindstrom, S, Liu, J, Long, J, Lubinski, J, Mai, PL, Makalic, E, Malone, KE, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Martens, JWM, McGuffog, L, Meindl, A, Miller, A, Milne, RL, Miron, P, Montagna, M, Mazoyer, S, Mulligan, AM, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olson, JE, Osorio, A, Park, SK, Peeters, PH, Peissel, B, Peterlongo, P, Peto, J, Phelan, CM, Pilarski, R, Poppe, B, Pylkaes, K, Radice, P, Rahman, N, Rantala, J, Rappaport, C, Rennert, G, Richardson, A, Robson, M, Romieu, I, Rudolph, A, Rutgers, EJ, Sanchez, M-J, Santella, RM, Sawyer, EJ, Schmidt, DF, Schmidt, MK, Schmutzler, RK, Schumacher, F, Scott, R, Senter, L, Sharma, P, Simard, J, Singer, CF, Sinilnikova, OM, Soucy, P, Southey, M, Steinemann, D, Stenmark-Askmalm, M, Stoppa-Lyonnet, D, Swerdlow, A, Szabo, CI, Tamimi, R, Tapper, W, Teixeira, MR, Teo, S-H, Terry, MB, Thomassen, M, Thompson, D, Tihomirova, L, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tsimiklis, H, Teule, A, Tumino, R, Tung, N, Turnbull, C, Ursin, G, van Deurzen, CHM, van Rensburg, EJ, Varon-Mateeva, R, Wang, Z, Wang-Gohrke, S, Weiderpass, E, Weitzel, JN, Whittemore, A, Wildiers, H, Winqvist, R, Yang, XR, Yannoukakos, D, Yao, S, Zamora, MP, Zheng, W, Hall, P, Kraft, P, Vachon, C, Slager, S, Chenevix-Trench, G, Pharoah, PDP, Monteiro, AAN, Garcia-Closas, M, Easton, DF, and Antoniou, AC
Abstract: Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
Published: 2016

135. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Zeng, C, Guo, X, Long, J, Kuchenbaecker, KB, Droit, A, Michailidou, K, Ghoussaini, M, Kar, S, Freeman, A, Hopper, JL, Milne, RL, Bolla, MK, Wang, Q, Dennis, J, Agata, S, Ahmed, S, Aittomaki, K, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arason, A, Arndt, V, Arun, BK, Arver, B, Bacot, F, Barrowdale, D, Baynes, C, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Blomqvist, C, Blot, WJ, Bogdanova, NV, Bojesen, SE, Bonanni, B, Borresen-Dale, A-L, Brand, JS, Brauch, H, Brennan, P, Brenner, H, Broeks, A, Bruening, T, Burwinkel, B, Buys, SS, Cai, Q, Caldes, T, Campbell, I, Carpenter, J, Chang-Claude, J, Choi, J-Y, Claes, KBM, Clarke, C, Cox, A, Cross, SS, Czene, K, Daly, MB, de la Hoya, M, De Leeneer, K, Devilee, P, Diez, O, Domchek, SM, Doody, M, Dorfling, CM, Doerk, T, dos-Santos-Silva, I, Dumont, M, Dwek, M, Dworniczak, B, Egan, K, Eilber, U, Einbeigi, Z, Ejlertsen, B, Ellis, S, Frost, D, Lalloo, F, Fasching, PA, Figueroa, J, Flyger, H, Friedlander, M, Friedman, E, Gambino, G, Gao, Y-T, Garber, J, Garcia-Closas, M, Gehrig, A, Damiola, F, Lesueur, F, Mazoyer, S, Stoppa-Lyonnet, D, Giles, GG, Godwin, AK, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Guenel, P, Haeberle, L, Haiman, CA, Hallberg, E, Hamann, U, Hansen, TVO, Hart, S, Hartikainen, JM, Hartman, M, Hassan, N, Healey, S, Hogervorst, FBL, Verhoef, S, Hendricks, CB, Hillemanns, P, Hollestelle, A, Hulick, PJ, Hunter, DJ, Imyanitov, EN, Isaacs, C, Ito, H, Jakubowska, A, Janavicius, R, Jaworska-Bieniek, K, Jensen, UB, John, EM, Beauparlant, CJ, Jones, M, Kabisch, M, Kang, D, Karlan, BY, Kauppila, S, Kerin, MJ, Khan, S, Khusnutdinova, E, Knight, JA, Konstantopoulou, I, Kraft, P, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C, Le Marchand, L, Lee, CN, Lee, MH, Lester, J, Li, J, Liljegren, A, Lindblom, A, Lophatananon, A, Lubinski, J, Mai, PL, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Matsuo, K, McGuffog, L, Meindl, A, Menegaux, F, Montagna, M, Muir, K, Mulligan, AM, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Newcomb, PA, Nord, S, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olswold, C, Osorio, A, Papi, L, Park-Simon, T-W, Paulsson-Karlsson, Y, Peeters, S, Peissel, B, Peterlongo, P, Peto, J, Pfeiler, G, Phelan, CM, Presneau, N, Radice, P, Rahman, N, Ramus, SJ, Rashid, MU, Rennert, G, Rhiem, K, Rudolph, A, Salani, R, Sangrajrang, S, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schoemaker, MJ, Schuermann, P, Seynaeve, C, Shen, C-Y, Shrubsole, MJ, Shu, X-O, Sigurdson, A, Singer, CF, Slager, S, Soucy, P, Southey, M, Steinemann, D, Swerdlow, A, Szabo, CI, Tchatchou, S, Teixeira, MR, Teo, SH, Terry, MB, Tessier, DC, Teule, A, Thomassen, M, Tihomirova, L, Tischkowitz, M, Toland, AE, Tung, N, Turnbull, C, van den Ouweland, AMW, van Rensburg, EJ, ven den Berg, D, Vijai, J, Wang-Gohrke, S, Weitzel, JN, Whittemore, AS, Winqvist, R, Wong, TY, Wu, AH, Yannoukakos, D, Yu, J-C, Pharoah, PDP, Hall, P, Chenevix-Trench, G, Dunning, AM, Simard, J, Couch, FJ, Antoniou, AC, Easton, DF, Zheng, W, Zeng, C, Guo, X, Long, J, Kuchenbaecker, KB, Droit, A, Michailidou, K, Ghoussaini, M, Kar, S, Freeman, A, Hopper, JL, Milne, RL, Bolla, MK, Wang, Q, Dennis, J, Agata, S, Ahmed, S, Aittomaki, K, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arason, A, Arndt, V, Arun, BK, Arver, B, Bacot, F, Barrowdale, D, Baynes, C, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Blomqvist, C, Blot, WJ, Bogdanova, NV, Bojesen, SE, Bonanni, B, Borresen-Dale, A-L, Brand, JS, Brauch, H, Brennan, P, Brenner, H, Broeks, A, Bruening, T, Burwinkel, B, Buys, SS, Cai, Q, Caldes, T, Campbell, I, Carpenter, J, Chang-Claude, J, Choi, J-Y, Claes, KBM, Clarke, C, Cox, A, Cross, SS, Czene, K, Daly, MB, de la Hoya, M, De Leeneer, K, Devilee, P, Diez, O, Domchek, SM, Doody, M, Dorfling, CM, Doerk, T, dos-Santos-Silva, I, Dumont, M, Dwek, M, Dworniczak, B, Egan, K, Eilber, U, Einbeigi, Z, Ejlertsen, B, Ellis, S, Frost, D, Lalloo, F, Fasching, PA, Figueroa, J, Flyger, H, Friedlander, M, Friedman, E, Gambino, G, Gao, Y-T, Garber, J, Garcia-Closas, M, Gehrig, A, Damiola, F, Lesueur, F, Mazoyer, S, Stoppa-Lyonnet, D, Giles, GG, Godwin, AK, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Guenel, P, Haeberle, L, Haiman, CA, Hallberg, E, Hamann, U, Hansen, TVO, Hart, S, Hartikainen, JM, Hartman, M, Hassan, N, Healey, S, Hogervorst, FBL, Verhoef, S, Hendricks, CB, Hillemanns, P, Hollestelle, A, Hulick, PJ, Hunter, DJ, Imyanitov, EN, Isaacs, C, Ito, H, Jakubowska, A, Janavicius, R, Jaworska-Bieniek, K, Jensen, UB, John, EM, Beauparlant, CJ, Jones, M, Kabisch, M, Kang, D, Karlan, BY, Kauppila, S, Kerin, MJ, Khan, S, Khusnutdinova, E, Knight, JA, Konstantopoulou, I, Kraft, P, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C, Le Marchand, L, Lee, CN, Lee, MH, Lester, J, Li, J, Liljegren, A, Lindblom, A, Lophatananon, A, Lubinski, J, Mai, PL, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Matsuo, K, McGuffog, L, Meindl, A, Menegaux, F, Montagna, M, Muir, K, Mulligan, AM, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Newcomb, PA, Nord, S, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olswold, C, Osorio, A, Papi, L, Park-Simon, T-W, Paulsson-Karlsson, Y, Peeters, S, Peissel, B, Peterlongo, P, Peto, J, Pfeiler, G, Phelan, CM, Presneau, N, Radice, P, Rahman, N, Ramus, SJ, Rashid, MU, Rennert, G, Rhiem, K, Rudolph, A, Salani, R, Sangrajrang, S, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schoemaker, MJ, Schuermann, P, Seynaeve, C, Shen, C-Y, Shrubsole, MJ, Shu, X-O, Sigurdson, A, Singer, CF, Slager, S, Soucy, P, Southey, M, Steinemann, D, Swerdlow, A, Szabo, CI, Tchatchou, S, Teixeira, MR, Teo, SH, Terry, MB, Tessier, DC, Teule, A, Thomassen, M, Tihomirova, L, Tischkowitz, M, Toland, AE, Tung, N, Turnbull, C, van den Ouweland, AMW, van Rensburg, EJ, ven den Berg, D, Vijai, J, Wang-Gohrke, S, Weitzel, JN, Whittemore, AS, Winqvist, R, Wong, TY, Wu, AH, Yannoukakos, D, Yu, J-C, Pharoah, PDP, Hall, P, Chenevix-Trench, G, Dunning, AM, Simard, J, Couch, FJ, Antoniou, AC, Easton, DF, and Zheng, W
Abstract: BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This
Published: 2016

136. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author: Machiela, MJ, Zhou, W, Karlins, E, Sampson, JN, Freedman, ND, Yang, Q, Hicks, B, Dagnall, C, Hautman, C, Jacobs, KB, Abnet, CC, Aldrich, MC, Amos, C, Amundadottir, LT, Arslan, AA, Beane-Freeman, LE, Berndt, SI, Black, A, Blot, WJ, Bock, CH, Bracci, PM, Brinton, LA, Bueno-de-Mesquita, HB, Burdett, L, Buring, JE, Butler, MA, Canzian, F, Carreon, T, Chaffee, KG, Chang, I-S, Chatterjee, N, Chen, C, Chen, K, Chung, CC, Cook, LS, Bou, MC, Cullen, M, Davis, FG, De Vivo, I, Ding, T, Doherty, J, Duell, EJ, Epstein, CG, Fan, J-H, Figueroa, JD, Fraumeni, JF, Friedenreich, CM, Fuchs, CS, Gallinger, S, Gao, Y-T, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Gaziano, JM, Giles, GG, Gillanders, EM, Giovannucci, EL, Goldin, L, Goldstein, AM, Haiman, CA, Hallmans, G, Hankinson, SE, Harris, CC, Henriksson, R, Holly, EA, Hong, Y-C, Hoover, RN, Hsiung, CA, Hu, N, Hu, W, Hunter, DJ, Hutchinson, A, Jenab, M, Johansen, C, Khaw, K-T, Kim, HN, Kim, YH, Kim, YT, Klein, AP, Klein, R, Koh, W-P, Kolonel, LN, Kooperberg, C, Kraft, P, Krogh, V, Kurtz, RC, LaCroix, A, Lan, Q, Landi, MT, Le Marchand, L, Li, D, Liang, X, Liao, LM, Lin, D, Liu, J, Lissowska, J, Lu, L, Magliocco, AM, Malats, N, Matsuo, K, McNeill, LH, McWilliams, RR, Melin, BS, Mirabello, L, Moore, L, Olson, SH, Orlow, I, Park, JY, Patino-Garcia, A, Peplonska, B, Peters, U, Petersen, GM, Pooler, L, Prescott, J, Prokunina-Olsson, L, Purdue, MP, Qiao, Y-L, Rajaraman, P, Real, FX, Riboli, E, Risch, HA, Rodriguez-Santiago, B, Ruder, AM, Savage, SA, Schumacher, F, Schwartz, AG, Schwartz, KL, Seow, A, Setiawan, VW, Severi, G, Shen, H, Sheng, X, Shin, M-H, Shu, X-O, Silverman, DT, Spitz, MR, Stevens, VL, Stolzenberg-Solomon, R, Stram, D, Tang, Z-Z, Taylor, PR, Teras, LR, Tobias, GS, Van den Berg, D, Visvanathan, K, Wacholder, S, Wang, J-C, Wang, Z, Wentzensen, N, Wheeler, W, White, E, Wiencke, JK, Wolpin, BM, Wong, MP, Wu, C, Wu, T, Wu, X, Wu, Y-L, Wunder, JS, Xia, L, Yang, HP, Yang, P-C, Yu, K, Zanetti, KA, Zeleniuch-Jacquotte, A, Zheng, W, Zhou, B, Ziegler, RG, Perez-Jurado, LA, Caporaso, NE, Rothman, N, Tucker, M, Dean, MC, Yeager, M, Chanock, SJ, Machiela, MJ, Zhou, W, Karlins, E, Sampson, JN, Freedman, ND, Yang, Q, Hicks, B, Dagnall, C, Hautman, C, Jacobs, KB, Abnet, CC, Aldrich, MC, Amos, C, Amundadottir, LT, Arslan, AA, Beane-Freeman, LE, Berndt, SI, Black, A, Blot, WJ, Bock, CH, Bracci, PM, Brinton, LA, Bueno-de-Mesquita, HB, Burdett, L, Buring, JE, Butler, MA, Canzian, F, Carreon, T, Chaffee, KG, Chang, I-S, Chatterjee, N, Chen, C, Chen, K, Chung, CC, Cook, LS, Bou, MC, Cullen, M, Davis, FG, De Vivo, I, Ding, T, Doherty, J, Duell, EJ, Epstein, CG, Fan, J-H, Figueroa, JD, Fraumeni, JF, Friedenreich, CM, Fuchs, CS, Gallinger, S, Gao, Y-T, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Gaziano, JM, Giles, GG, Gillanders, EM, Giovannucci, EL, Goldin, L, Goldstein, AM, Haiman, CA, Hallmans, G, Hankinson, SE, Harris, CC, Henriksson, R, Holly, EA, Hong, Y-C, Hoover, RN, Hsiung, CA, Hu, N, Hu, W, Hunter, DJ, Hutchinson, A, Jenab, M, Johansen, C, Khaw, K-T, Kim, HN, Kim, YH, Kim, YT, Klein, AP, Klein, R, Koh, W-P, Kolonel, LN, Kooperberg, C, Kraft, P, Krogh, V, Kurtz, RC, LaCroix, A, Lan, Q, Landi, MT, Le Marchand, L, Li, D, Liang, X, Liao, LM, Lin, D, Liu, J, Lissowska, J, Lu, L, Magliocco, AM, Malats, N, Matsuo, K, McNeill, LH, McWilliams, RR, Melin, BS, Mirabello, L, Moore, L, Olson, SH, Orlow, I, Park, JY, Patino-Garcia, A, Peplonska, B, Peters, U, Petersen, GM, Pooler, L, Prescott, J, Prokunina-Olsson, L, Purdue, MP, Qiao, Y-L, Rajaraman, P, Real, FX, Riboli, E, Risch, HA, Rodriguez-Santiago, B, Ruder, AM, Savage, SA, Schumacher, F, Schwartz, AG, Schwartz, KL, Seow, A, Setiawan, VW, Severi, G, Shen, H, Sheng, X, Shin, M-H, Shu, X-O, Silverman, DT, Spitz, MR, Stevens, VL, Stolzenberg-Solomon, R, Stram, D, Tang, Z-Z, Taylor, PR, Teras, LR, Tobias, GS, Van den Berg, D, Visvanathan, K, Wacholder, S, Wang, J-C, Wang, Z, Wentzensen, N, Wheeler, W, White, E, Wiencke, JK, Wolpin, BM, Wong, MP, Wu, C, Wu, T, Wu, X, Wu, Y-L, Wunder, JS, Xia, L, Yang, HP, Yang, P-C, Yu, K, Zanetti, KA, Zeleniuch-Jacquotte, A, Zheng, W, Zhou, B, Ziegler, RG, Perez-Jurado, LA, Caporaso, NE, Rothman, N, Tucker, M, Dean, MC, Yeager, M, and Chanock, SJ
Abstract: To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
Published: 2016

137. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Author: Franco, EL, Khankari, NK, Shu, X-O, Wen, W, Kraft, P, Lindstrom, S, Peters, U, Schildkraut, J, Schumacher, F, Bofetta, P, Risch, A, Bickeboeller, H, Amos, CI, Easton, D, Eeles, RA, Gruber, SB, Haiman, CA, Hunter, DJ, Chanock, SJ, Pierce, BL, Zheng, W, Franco, EL, Khankari, NK, Shu, X-O, Wen, W, Kraft, P, Lindstrom, S, Peters, U, Schildkraut, J, Schumacher, F, Bofetta, P, Risch, A, Bickeboeller, H, Amos, CI, Easton, D, Eeles, RA, Gruber, SB, Haiman, CA, Hunter, DJ, Chanock, SJ, Pierce, BL, and Zheng, W
Abstract: BACKGROUND: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. METHODS AND FINDINGS: A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. CONCLUSIONS: Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the
Published: 2016

138. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Author: Fritsche, LG, Igl, W, Bailey, JNC, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, MI, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Hong, O, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Starke, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-M, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, SV, Grunin, M, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Igo, RP, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, AI, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Haines, JL, Iyengar, SK, Weber, BHF, Abecasis, GR, Heid, IM, Fritsche, LG, Igl, W, Bailey, JNC, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, MI, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Hong, O, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Starke, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-M, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, SV, Grunin, M, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Igo, RP, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, AI, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Haines, JL, Iyengar, SK, Weber, BHF, Abecasis, GR, and Heid, IM
Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
Published: 2016

139. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Author: Southey, MC, Goldgar, DE, Winqvist, R, Pylkas, K, Couch, F, Tischkowitz, M, Foulkes, WD, Dennis, J, Michailidou, K, van Rensburg, EJ, Heikkinen, T, Nevanlinna, H, Hopper, JL, Doerk, T, Claes, KBM, Reis-Filho, J, Teo, ZL, Radice, P, Catucci, I, Peterlongo, P, Tsimiklis, H, Odefrey, FA, Dowty, JG, Schmidt, MK, Broeks, A, Hogervorst, FB, Verhoef, S, Carpenter, J, Clarke, C, Scott, RJ, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Peto, J, dos-Santos-Silva, I, Fletcher, O, Johnson, N, Bolla, MK, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Marme, F, Burwinkel, B, Yang, R, Guenel, P, Therese, T, Menegaux, F, Sanchez, M, Bojesen, S, Nielsen, SF, Flyger, H, Benitez, J, Pilar Zamora, M, Arias Perez, JI, Menendez, P, Anton-Culver, H, Neuhausen, S, Ziogas, A, Clarke, CA, Brenner, H, Arndt, V, Stegmaier, C, Brauch, H, Bruening, T, Ko, Y-D, Muranen, TA, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Antonenkova, NN, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Spurdle, AB, Wauters, E, Smeets, D, Beuselinck, B, Floris, G, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Olson, JE, Vachon, C, Pankratz, VS, McLean, C, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Kristensen, V, Alnaes, GG, Zheng, W, Hunter, DJ, Lindstrom, S, Hankinson, SE, Kraft, P, Andrulis, I, Knight, JA, Glendon, G, Mulligan, AM, Jukkola-Vuorinen, A, Grip, M, Kauppila, S, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Hollestelle, A, Garcia-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Czene, K, Darabi, H, Eriksson, M, Eccles, DM, Rafiq, S, Tapper, WJ, Gerty, SM, Hooning, MJ, Martens, JWM, Collee, JM, Tilanus-Linthorst, M, Hall, P, Li, J, Brand, JS, Humphreys, K, Cox, A, Reed, MWR, Luccarini, C, Baynes, C, Dunning, AM, Hamann, U, Torres, D, Ulmer, HU, Ruediger, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Slager, S, Toland, AE, Ambrosone, CB, Yannoukakos, D, Swerdlow, A, Ashworth, A, Orr, N, Jones, M, Gonzalez-Neira, A, Pita, G, Rosario Alonso, M, Alvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, Simard, J, Dumont, M, Soucy, P, Eeles, R, Muir, K, Wiklund, F, Gronberg, H, Schleutker, J, Nordestgaard, BG, Weischer, M, Travis, RC, Neal, D, Donovan, JL, Hamdy, FC, Khaw, K-T, Stanford, JL, Blot, WJ, Thibodeau, S, Schaid, DJ, Kelley, JL, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Butterbach, K, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Renner, SP, Hartmann, A, Hein, A, Ruebner, M, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I, Lambretchs, S, Doherty, JA, Rossing, MA, Nickels, S, Eilber, U, Wang-Gohrke, S, Odunsi, K, Sucheston-Campbell, LE, Friel, G, Lurie, G, Killeen, JL, Wilkens, LR, Goodman, MT, Runnebaum, I, Hillemanns, PA, Pelttari, LM, Butzow, R, Modugno, F, Edwards, RP, Ness, RB, Moysich, KB, du Bois, A, Heitz, F, Harter, P, Kommoss, S, Karlan, BY, Walsh, C, Lester, J, Jensen, A, Kjaer, SK, Hogdall, E, Peissel, B, Bonanni, B, Bernard, L, Goode, EL, Fridley, BL, Vierkant, RA, Cunningham, JM, Larson, MC, Fogarty, ZC, Kalli, KR, Liang, D, Lu, KH, Hildebrandt, MAT, Wu, X, Levine, DA, Dao, F, Bisogna, M, Berchuck, A, Iversen, ES, Marks, JR, Akushevich, L, Cramer, DW, Schildkraut, J, Terry, KL, Poole, EM, Stampfer, M, Tworoger, SS, Bandera, EV, Orlow, I, Olson, SH, Bjorge, L, Salvesen, HB, van Altena, AM, Aben, KKH, Kiemeney, LA, Massuger, LFAG, Pejovic, T, Bean, Y, Brooks-Wilson, A, Kelemen, LE, Cook, LS, Le, ND, Grski, B, Gronwald, J, Menkiszak, J, Hogdall, CK, Lundvall, L, Nedergaard, L, Engelholm, SA, Dicks, E, Tyrer, J, Campbell, I, McNeish, I, Paul, J, Siddiqui, N, Glasspool, R, Whittemore, AS, Rothstein, JH, McGuire, V, Sieh, W, Cai, H, Shu, X-O, Teten, RT, Sutphen, R, McLaughlin, JR, Narod, SA, Phelan, CM, Monteiro, AN, Fenstermacher, D, Lin, H-Y, Permuth, JB, Sellers, TA, Chen, YA, Tsai, Y-Y, Chen, Z, Gentry-Maharaj, A, Gayther, SA, Ramus, SJ, Menon, U, Wu, AH, Pearce, CL, Van den Berg, D, Pike, MC, Dansonka-Mieszkowska, A, Plisiecka-Halasa, J, Moes-Sosnowska, J, Kupryjanczyk, J, Pharoah, PDP, Song, H, Winship, I, Chenevix-Trench, G, Giles, GG, Tavtigian, SV, Easton, DF, Milne, RL, Southey, MC, Goldgar, DE, Winqvist, R, Pylkas, K, Couch, F, Tischkowitz, M, Foulkes, WD, Dennis, J, Michailidou, K, van Rensburg, EJ, Heikkinen, T, Nevanlinna, H, Hopper, JL, Doerk, T, Claes, KBM, Reis-Filho, J, Teo, ZL, Radice, P, Catucci, I, Peterlongo, P, Tsimiklis, H, Odefrey, FA, Dowty, JG, Schmidt, MK, Broeks, A, Hogervorst, FB, Verhoef, S, Carpenter, J, Clarke, C, Scott, RJ, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Peto, J, dos-Santos-Silva, I, Fletcher, O, Johnson, N, Bolla, MK, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Marme, F, Burwinkel, B, Yang, R, Guenel, P, Therese, T, Menegaux, F, Sanchez, M, Bojesen, S, Nielsen, SF, Flyger, H, Benitez, J, Pilar Zamora, M, Arias Perez, JI, Menendez, P, Anton-Culver, H, Neuhausen, S, Ziogas, A, Clarke, CA, Brenner, H, Arndt, V, Stegmaier, C, Brauch, H, Bruening, T, Ko, Y-D, Muranen, TA, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Antonenkova, NN, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Spurdle, AB, Wauters, E, Smeets, D, Beuselinck, B, Floris, G, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Olson, JE, Vachon, C, Pankratz, VS, McLean, C, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Kristensen, V, Alnaes, GG, Zheng, W, Hunter, DJ, Lindstrom, S, Hankinson, SE, Kraft, P, Andrulis, I, Knight, JA, Glendon, G, Mulligan, AM, Jukkola-Vuorinen, A, Grip, M, Kauppila, S, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Hollestelle, A, Garcia-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Czene, K, Darabi, H, Eriksson, M, Eccles, DM, Rafiq, S, Tapper, WJ, Gerty, SM, Hooning, MJ, Martens, JWM, Collee, JM, Tilanus-Linthorst, M, Hall, P, Li, J, Brand, JS, Humphreys, K, Cox, A, Reed, MWR, Luccarini, C, Baynes, C, Dunning, AM, Hamann, U, Torres, D, Ulmer, HU, Ruediger, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Slager, S, Toland, AE, Ambrosone, CB, Yannoukakos, D, Swerdlow, A, Ashworth, A, Orr, N, Jones, M, Gonzalez-Neira, A, Pita, G, Rosario Alonso, M, Alvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, Simard, J, Dumont, M, Soucy, P, Eeles, R, Muir, K, Wiklund, F, Gronberg, H, Schleutker, J, Nordestgaard, BG, Weischer, M, Travis, RC, Neal, D, Donovan, JL, Hamdy, FC, Khaw, K-T, Stanford, JL, Blot, WJ, Thibodeau, S, Schaid, DJ, Kelley, JL, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Butterbach, K, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Renner, SP, Hartmann, A, Hein, A, Ruebner, M, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I, Lambretchs, S, Doherty, JA, Rossing, MA, Nickels, S, Eilber, U, Wang-Gohrke, S, Odunsi, K, Sucheston-Campbell, LE, Friel, G, Lurie, G, Killeen, JL, Wilkens, LR, Goodman, MT, Runnebaum, I, Hillemanns, PA, Pelttari, LM, Butzow, R, Modugno, F, Edwards, RP, Ness, RB, Moysich, KB, du Bois, A, Heitz, F, Harter, P, Kommoss, S, Karlan, BY, Walsh, C, Lester, J, Jensen, A, Kjaer, SK, Hogdall, E, Peissel, B, Bonanni, B, Bernard, L, Goode, EL, Fridley, BL, Vierkant, RA, Cunningham, JM, Larson, MC, Fogarty, ZC, Kalli, KR, Liang, D, Lu, KH, Hildebrandt, MAT, Wu, X, Levine, DA, Dao, F, Bisogna, M, Berchuck, A, Iversen, ES, Marks, JR, Akushevich, L, Cramer, DW, Schildkraut, J, Terry, KL, Poole, EM, Stampfer, M, Tworoger, SS, Bandera, EV, Orlow, I, Olson, SH, Bjorge, L, Salvesen, HB, van Altena, AM, Aben, KKH, Kiemeney, LA, Massuger, LFAG, Pejovic, T, Bean, Y, Brooks-Wilson, A, Kelemen, LE, Cook, LS, Le, ND, Grski, B, Gronwald, J, Menkiszak, J, Hogdall, CK, Lundvall, L, Nedergaard, L, Engelholm, SA, Dicks, E, Tyrer, J, Campbell, I, McNeish, I, Paul, J, Siddiqui, N, Glasspool, R, Whittemore, AS, Rothstein, JH, McGuire, V, Sieh, W, Cai, H, Shu, X-O, Teten, RT, Sutphen, R, McLaughlin, JR, Narod, SA, Phelan, CM, Monteiro, AN, Fenstermacher, D, Lin, H-Y, Permuth, JB, Sellers, TA, Chen, YA, Tsai, Y-Y, Chen, Z, Gentry-Maharaj, A, Gayther, SA, Ramus, SJ, Menon, U, Wu, AH, Pearce, CL, Van den Berg, D, Pike, MC, Dansonka-Mieszkowska, A, Plisiecka-Halasa, J, Moes-Sosnowska, J, Kupryjanczyk, J, Pharoah, PDP, Song, H, Winship, I, Chenevix-Trench, G, Giles, GG, Tavtigian, SV, Easton, DF, and Milne, RL
Abstract: BACKGROUND: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. METHODS: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. RESULTS: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. CONCLUSIONS: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
Published: 2016

140. Patient Knowledge and Beliefs About Knee Osteoarthritis After Anterior Cruciate Ligament Injury and Reconstruction

Author: Bennell, KL, van Ginckel, A, Kean, CO, Nelligan, RK, French, SD, Stokes, M, Pietrosimone, B, Blackburn, T, Batt, M, Hunter, DJ, Spiers, L, Hinman, RS, Bennell, KL, van Ginckel, A, Kean, CO, Nelligan, RK, French, SD, Stokes, M, Pietrosimone, B, Blackburn, T, Batt, M, Hunter, DJ, Spiers, L, and Hinman, RS
Abstract: OBJECTIVE: To explore patients' knowledge and beliefs about osteoarthritis (OA) and OA risk following anterior cruciate ligament (ACL) injury, to explore the extent to which information about these risks is provided by health professionals, and to examine associations among participant characteristics, knowledge, and risk beliefs and health professional advice. METHODS: A custom-designed survey was conducted in Australian and American adults who sustained an ACL injury, with or without reconstruction, 1-5 years prior. The survey comprised 3 sections: participant characteristics, knowledge about OA and OA risk, and health professional advice. RESULTS: Complete data sets from 233 eligible respondents were analyzed. Most (70%, n = 164) rated themselves as being at greater risk of OA than their healthy peers, although only 56% (n = 130) were able to identify the correct OA definition. While most agreed that ACL (73%, n = 168) and/or meniscal injuries (n = 181, 78%) increase the risk of OA, 65% (n = 152) believed that ACL reconstruction reduced the risk of OA, or they did not know. A total of 27% (n = 62) recalled discussing their OA risk with a health professional. Participants who were female, younger, or had a lower body mass index or higher physical activity level were more likely to recognize meniscal tears and meniscectomy as risk factors of OA. A history of professional advice was associated with beliefs about increased OA risks. CONCLUSION: Patients sustaining an ACL injury require better education from health professionals about OA as a disease entity and their elevated risk of OA, irrespective of whether or not they undergo surgical reconstruction.
Published: 2016

141. Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

Author: Teumer, A, Qi, QB, Nethander, M, Aschard, H, Bandinelli, S, Beekman, M, Berndt, SI, Bidlingmaier, M, Broer, Linda, Cappola, A, Ceda, G P, Chanock, S, Chen, MH, Chen, T C, Chen, YDI, Chung, JW, Miglianico, F D, Eriksson, J, Ferrucci, L, Friedrich, N, Gnewuch, C, Goodarzi, MO, Grarup, N, Guo, T W, Hammer, E, Hayes, RB, Hicks, AA, Hofman, Bert, Houwing-Duistermaat, JJ, Hu, F, Hunter, DJ, Husemoen, LL, Isaacs, Aaron, Jacobs, KB, Janssen, J.A.M.J.L., Jansson, JO, Jehmlich, N, Johnson, S, Juul, A, Karlsson, M, Kilpelainen, TO, Kovacs, P, Kraft, P, Li, C, Linneberg, A, Liu, YM, Loos, RJF, Lorentzon, M, Lu, YC, Maggio, M, Magi, R, Meigs, J, Mellstrom, D, Nauck, M, Newman, AB, Pollak, MN, Pramstaller, PP, Prokopenko, I, Psaty, BM, Reincke, M, Rimm, EB, Rotter, JI, Saint Pierre, A, Schurmann, C, Seshadri, S, Sjogren, K, Slagboom, PE (Eline), Strickler, H D, Stumvoll, M, Suh, Y S, Sun, Q, Zhang, CL, Svensson, J, Tanaka, T, Tare, A, Tonjes, A, Uh, HW, Duijn, Cornelia, van Heemst, D, Vandenput, L, Vasan, RS, Volker, U, Willems, SM, Ohlsson, C, Wallaschofski, H, Kaplan, RC, Teumer, A, Qi, QB, Nethander, M, Aschard, H, Bandinelli, S, Beekman, M, Berndt, SI, Bidlingmaier, M, Broer, Linda, Cappola, A, Ceda, G P, Chanock, S, Chen, MH, Chen, T C, Chen, YDI, Chung, JW, Miglianico, F D, Eriksson, J, Ferrucci, L, Friedrich, N, Gnewuch, C, Goodarzi, MO, Grarup, N, Guo, T W, Hammer, E, Hayes, RB, Hicks, AA, Hofman, Bert, Houwing-Duistermaat, JJ, Hu, F, Hunter, DJ, Husemoen, LL, Isaacs, Aaron, Jacobs, KB, Janssen, J.A.M.J.L., Jansson, JO, Jehmlich, N, Johnson, S, Juul, A, Karlsson, M, Kilpelainen, TO, Kovacs, P, Kraft, P, Li, C, Linneberg, A, Liu, YM, Loos, RJF, Lorentzon, M, Lu, YC, Maggio, M, Magi, R, Meigs, J, Mellstrom, D, Nauck, M, Newman, AB, Pollak, MN, Pramstaller, PP, Prokopenko, I, Psaty, BM, Reincke, M, Rimm, EB, Rotter, JI, Saint Pierre, A, Schurmann, C, Seshadri, S, Sjogren, K, Slagboom, PE (Eline), Strickler, H D, Stumvoll, M, Suh, Y S, Sun, Q, Zhang, CL, Svensson, J, Tanaka, T, Tare, A, Tonjes, A, Uh, HW, Duijn, Cornelia, van Heemst, D, Vandenput, L, Vasan, RS, Volker, U, Willems, SM, Ohlsson, C, Wallaschofski, H, and Kaplan, RC
Published: 2016

142. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author: Kilpelainen, TO, Carli, J F M, Skowronski, A A, Sun, Q, Kriebel, J, Feitosa, MF, Hedman, AK, Drong, AW, Hayes, J E, Zhao, JH, Pers, TH, Schick, U, Grarup, N, Kutalik, Z, Trompet, S, Mangino, M, Kristiansson, K, Beekman, M, Lyytikainen, LP, Eriksson, J, Henneman, Peter, Lahti, J, Tanaka, T, Luan, JA, Del Greco, F, Pasko, D, Renstrom, F, Willems, SM, Mahajan, A, Rose, LM, Guo, XQ, Liu, YM, Kleber, ME, Perusse, L, Gaunt, T, Ahluwalia, TS, Sung, YJ, Ramos, YF, Amin, Najaf, Amuzu, A, Barroso, I, Bellis, C, Blangero, J, Buckley, BM, Bohringer, S, Chen, YDI, de Craen, A J N, Crosslin, DR, Dale, CE, Dastani, Z, Day, FR, Deelen, J, Delgado, GE, Demirkan, Ayse, Finucane, FM, Ford, I, Garcia, ME, Gieger, C, Gustafsson, S, Hallmans, G, Hankinson, SE, Havulinna, AS, Herder, Cindy, Hernandez, D, Hicks, AA, Hunter, DJ, Illig, T, Ingelsson, E, Ioan-Facsinay, A, Jansson, JO, Jenny, NS, Jorgensen, ME, Jorgensen, T, Karlsson, M, Koenig, W, Kraft, P, Kwekkeboom, J, Laatikainen, T, Ladwig, KH, LeDuc, C A, Lowe, G, Lu, YC, Marques-Vidal, P, Meisinger, C, Menni, C, Morris, AP, Myers, RH, Mannisto, S, Nalls, MA, Paternoster, L, Peters, A, Pradhan, A D, Rankinen, T, Rasmussen-Torvik, LJ, Rathmann, W, Rice, TK, Richards, JB, Ridker, PM, Sattar, N, Savage, DB, Soderberg, S, Timpson, NJ, Vandenput, L, van Heemst, D, Uh, HW, Vohl, MC, Walker, M, Wichmann, HE, Widen, E, Wood, AR, Yao, J, Zeller, T, Zhang, YY, Meulenbelt, I, Kloppenburg, M, Astrup, A, Sorensen, TIA, Sarzynski, MA, Rao, DC, Jousilahti, P, Vartiainen, E, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Kajantie, E, Osmond, C, Palotie, A, Eriksson, JG, Heliovaara, M, Knekt, PB, Koskinen, S, Jula, A, Perola, M, Huupponen, R K, Viikari, JS, Kahonen, M, Lehtimaki, T, Raitakari, OT, Mellstrom, D, Lorentzon, M, Casas, JP, Bandinelli, S, Marz, W, Isaacs, Aaron, van Dijk, KW, Duijn, Cornelia, Harris, TB, Bouchard, C, Allison, MA, Chasman, DI, Ohlsson, C, Lind, L, Scott, RA, Langenberg, C, Wareham, NJ, Ferrucci, L, Frayling, TM, Pramstaller, PP, Borecki, IB, Waterworth, DM, Bergmann, S, Waeber, G, Vollenweider, P, Vestergaard, H, Hansen, T, Pedersen, O, Hu, FB, Slagboom, PE (Eline), Grallert, H, Spector, TD, Jukema, JW, Klein, RJ, Schadt, EE, Franks, PW, Lindgren, CM, Leibel, R L, Loos, RJF, Kilpelainen, TO, Carli, J F M, Skowronski, A A, Sun, Q, Kriebel, J, Feitosa, MF, Hedman, AK, Drong, AW, Hayes, J E, Zhao, JH, Pers, TH, Schick, U, Grarup, N, Kutalik, Z, Trompet, S, Mangino, M, Kristiansson, K, Beekman, M, Lyytikainen, LP, Eriksson, J, Henneman, Peter, Lahti, J, Tanaka, T, Luan, JA, Del Greco, F, Pasko, D, Renstrom, F, Willems, SM, Mahajan, A, Rose, LM, Guo, XQ, Liu, YM, Kleber, ME, Perusse, L, Gaunt, T, Ahluwalia, TS, Sung, YJ, Ramos, YF, Amin, Najaf, Amuzu, A, Barroso, I, Bellis, C, Blangero, J, Buckley, BM, Bohringer, S, Chen, YDI, de Craen, A J N, Crosslin, DR, Dale, CE, Dastani, Z, Day, FR, Deelen, J, Delgado, GE, Demirkan, Ayse, Finucane, FM, Ford, I, Garcia, ME, Gieger, C, Gustafsson, S, Hallmans, G, Hankinson, SE, Havulinna, AS, Herder, Cindy, Hernandez, D, Hicks, AA, Hunter, DJ, Illig, T, Ingelsson, E, Ioan-Facsinay, A, Jansson, JO, Jenny, NS, Jorgensen, ME, Jorgensen, T, Karlsson, M, Koenig, W, Kraft, P, Kwekkeboom, J, Laatikainen, T, Ladwig, KH, LeDuc, C A, Lowe, G, Lu, YC, Marques-Vidal, P, Meisinger, C, Menni, C, Morris, AP, Myers, RH, Mannisto, S, Nalls, MA, Paternoster, L, Peters, A, Pradhan, A D, Rankinen, T, Rasmussen-Torvik, LJ, Rathmann, W, Rice, TK, Richards, JB, Ridker, PM, Sattar, N, Savage, DB, Soderberg, S, Timpson, NJ, Vandenput, L, van Heemst, D, Uh, HW, Vohl, MC, Walker, M, Wichmann, HE, Widen, E, Wood, AR, Yao, J, Zeller, T, Zhang, YY, Meulenbelt, I, Kloppenburg, M, Astrup, A, Sorensen, TIA, Sarzynski, MA, Rao, DC, Jousilahti, P, Vartiainen, E, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Kajantie, E, Osmond, C, Palotie, A, Eriksson, JG, Heliovaara, M, Knekt, PB, Koskinen, S, Jula, A, Perola, M, Huupponen, R K, Viikari, JS, Kahonen, M, Lehtimaki, T, Raitakari, OT, Mellstrom, D, Lorentzon, M, Casas, JP, Bandinelli, S, Marz, W, Isaacs, Aaron, van Dijk, KW, Duijn, Cornelia, Harris, TB, Bouchard, C, Allison, MA, Chasman, DI, Ohlsson, C, Lind, L, Scott, RA, Langenberg, C, Wareham, NJ, Ferrucci, L, Frayling, TM, Pramstaller, PP, Borecki, IB, Waterworth, DM, Bergmann, S, Waeber, G, Vollenweider, P, Vestergaard, H, Hansen, T, Pedersen, O, Hu, FB, Slagboom, PE (Eline), Grallert, H, Spector, TD, Jukema, JW, Klein, RJ, Schadt, EE, Franks, PW, Lindgren, CM, Leibel, R L, and Loos, RJF
Published: 2016

143. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author: Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, JA, Magi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM (Ilja), Perusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, M T, Snieder, H, Stancakova, A, Sung, YJ, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, Sara M., Wong, A, Zhang, WH, Albrecht, E, Alves, AC, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Bluher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, YDI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'Avila, F, de Geus, EJC, Dedoussis, G, Dimitriou, M, Doring, A, Eriksson, JG, Farmaki, AE, Farrall, M, Ferreira, T, Fischer, K, Forouhi, NG, Friedrich, N, Gjesing, AP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Grassler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliovaara, M, Hillege, H, Hofman, Bert, Holmen, O, Homuth, G, Hottenga, JJ (Jouke Jan), Hui, JN, Husemoen, LL, Hysi, PG, Isaacs, Aaron, Ittermann, T, Jalilzadeh, S, James, AL, Jorgensen, T, Jousilahti, P, Jula, A, Justesen, JM, Justice, AE, Kahonen, M, Karaleftheri, M, Khaw, KT, Keinanen-Kiukaanniemi, SM, Kinnunen, L, Knekt, PB, Koistinen, HA, Kolcic, I, Kooner, IK, Koskinen, S, Kovacs, P, Kyriakou, T, Laitinen, T, Langenberg, C, Lewin, AM, Lichtner, P, Lindgren, CM, Lindstrom, J, Linneberg, A, Lorbeer, R, Lorentzon, M, Luben, R, Lyssenko, V, Mannisto, S, Manunta, P, Leach, IM, McArdle, WL, McKnight, B, Mohlke, KL, Mihailov, E, Milani, L, Mills, R, Montasser, ME, Morris, AP, Muller, G, Musk, AW, Narisu, N, Ong, KK, Oostra, B, Osmond, C, Palotie, A, Pankow, JS, Paternoster, L, Penninx, BW, Pichler, I, Pilia, MG, Polasek, O, Pramstaller, PP, Raitakari, OT, Rankinen, T, Rao, DC, Rayner, NW, Ribel-Madsen, R, Rice, TK, Richards, M, Ridker, PM, Rivadeneira, Fernando, Ryan, KA, Sanna, S, Sarzynski, MA, Scholtens, s, Scott, RA, Sebert, S, Southam, L, Sparso, TH, Steinthorsdottir, V, Stirrups, K, Stolk, RP (Ronald), Strauch, K, Stringham, HM, Swertz, MA, Swift, AJ, Tonjes, A, Tsafantakis, E, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vandenput, L, Vartiainen, E, Venturini, C, Verweij, N (Niek), Viikari, JS, Vitart, V, Vohl, MC, Vonk, JM, Waeber, G, Widen, E, Willemsen, G, Wilsgaard, T, Winkler, TW, Wright, AF, Yerges-Armstrong, LM, Zhao, JH, Zillikens, M.C., Boomsma, DI, Bouchard, C, Chambers, JC, Chasman, DI, Cusi, D, Gansevoort, RT, Gieger, C, Hansen, T, Hicks, AA, Hu, F, Hveem, K, Jarvelin, MR, Kajantie, E, Kooner, JS, Kuh, D, Kuusisto, J, Laakso, M, Lakka, TA, Lehtimaki, T, Metspalu, A, Njolstad, I, Ohlsson, C, Oldehinkel, Albertine J., Palmer, LJ, Pedersen, O, Perola, M, Peters, A, Psaty, BM, Puolijoki, H, Rauramaa, R, Rudan, I, Salomaa, V, Schwarz, PEH, Shudiner, A R, Smit, JH, Sorensen, TIA, Spector, TD, Stefansson, K, Stumvoll, M, Tremblay, A, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Volker, U, Vollenweider, P, Wareham, NJ, Watkins, H, Wilson, JF, Zeggini, E, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Duijn, Cornelia, Fox, C, Groop, LC, Heid, IM, Hunter, DJ, Kaplan, RC, McCarthy, MI, North, KE, O'Connell, JR, Schlessinger, D, Thorsteinsdottir, U, Strachan, DP, Frayling, T, Hirschhorn, JN, Muller-Nurasyid, M, Loos, RJF, Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, JA, Magi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM (Ilja), Perusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, M T, Snieder, H, Stancakova, A, Sung, YJ, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, Sara M., Wong, A, Zhang, WH, Albrecht, E, Alves, AC, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Bluher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, YDI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'Avila, F, de Geus, EJC, Dedoussis, G, Dimitriou, M, Doring, A, Eriksson, JG, Farmaki, AE, Farrall, M, Ferreira, T, Fischer, K, Forouhi, NG, Friedrich, N, Gjesing, AP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Grassler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliovaara, M, Hillege, H, Hofman, Bert, Holmen, O, Homuth, G, Hottenga, JJ (Jouke Jan), Hui, JN, Husemoen, LL, Hysi, PG, Isaacs, Aaron, Ittermann, T, Jalilzadeh, S, James, AL, Jorgensen, T, Jousilahti, P, Jula, A, Justesen, JM, Justice, AE, Kahonen, M, Karaleftheri, M, Khaw, KT, Keinanen-Kiukaanniemi, SM, Kinnunen, L, Knekt, PB, Koistinen, HA, Kolcic, I, Kooner, IK, Koskinen, S, Kovacs, P, Kyriakou, T, Laitinen, T, Langenberg, C, Lewin, AM, Lichtner, P, Lindgren, CM, Lindstrom, J, Linneberg, A, Lorbeer, R, Lorentzon, M, Luben, R, Lyssenko, V, Mannisto, S, Manunta, P, Leach, IM, McArdle, WL, McKnight, B, Mohlke, KL, Mihailov, E, Milani, L, Mills, R, Montasser, ME, Morris, AP, Muller, G, Musk, AW, Narisu, N, Ong, KK, Oostra, B, Osmond, C, Palotie, A, Pankow, JS, Paternoster, L, Penninx, BW, Pichler, I, Pilia, MG, Polasek, O, Pramstaller, PP, Raitakari, OT, Rankinen, T, Rao, DC, Rayner, NW, Ribel-Madsen, R, Rice, TK, Richards, M, Ridker, PM, Rivadeneira, Fernando, Ryan, KA, Sanna, S, Sarzynski, MA, Scholtens, s, Scott, RA, Sebert, S, Southam, L, Sparso, TH, Steinthorsdottir, V, Stirrups, K, Stolk, RP (Ronald), Strauch, K, Stringham, HM, Swertz, MA, Swift, AJ, Tonjes, A, Tsafantakis, E, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vandenput, L, Vartiainen, E, Venturini, C, Verweij, N (Niek), Viikari, JS, Vitart, V, Vohl, MC, Vonk, JM, Waeber, G, Widen, E, Willemsen, G, Wilsgaard, T, Winkler, TW, Wright, AF, Yerges-Armstrong, LM, Zhao, JH, Zillikens, M.C., Boomsma, DI, Bouchard, C, Chambers, JC, Chasman, DI, Cusi, D, Gansevoort, RT, Gieger, C, Hansen, T, Hicks, AA, Hu, F, Hveem, K, Jarvelin, MR, Kajantie, E, Kooner, JS, Kuh, D, Kuusisto, J, Laakso, M, Lakka, TA, Lehtimaki, T, Metspalu, A, Njolstad, I, Ohlsson, C, Oldehinkel, Albertine J., Palmer, LJ, Pedersen, O, Perola, M, Peters, A, Psaty, BM, Puolijoki, H, Rauramaa, R, Rudan, I, Salomaa, V, Schwarz, PEH, Shudiner, A R, Smit, JH, Sorensen, TIA, Spector, TD, Stefansson, K, Stumvoll, M, Tremblay, A, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Volker, U, Vollenweider, P, Wareham, NJ, Watkins, H, Wilson, JF, Zeggini, E, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Duijn, Cornelia, Fox, C, Groop, LC, Heid, IM, Hunter, DJ, Kaplan, RC, McCarthy, MI, North, KE, O'Connell, JR, Schlessinger, D, Thorsteinsdottir, U, Strachan, DP, Frayling, T, Hirschhorn, JN, Muller-Nurasyid, M, and Loos, RJF
Published: 2016

144. y New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author: Lu, YC, Day, FR, Gustafsson, S, Buchkovich, ML, Na, JB, Bataille, V, Cousminer, DL, Dastani, Z, Drong, AW, Esko, T, Evans, DM, Falchi, M, Feitosa, MF, Ferreira, T, Hedman, AK, Haring, R, Hysi, PG, Iles, MM, Justice, AE, Kanoni, S, Lagou, V, Li, R, Li, X, Locke, A, Lu, C, Magi, R, Perry, JRB, Pers, TH, Qi, QB, Sanna, M, Schmidt, EM, Scott, WR, Shungin, D, Teumer, A, Vinkhuyzen, AAE, Walker, RW, Westra, HJ, Zhang, MF, Zhang, WH, Zhao, JH, Zhu, ZH, Afzal, U, Ahluwalia, TS, Bakker, SJL, Bellis, C, Bonnefond, A, Borodulin, K, Buchman, AS, Cederholm, T, Choh, AC, Choi, HJ, Curran, JE, de Groot, LCPGM (Lisette), De Jager, PL, Dhonukshe-Rutten, RAM, Enneman, Anke, Eury, E, Evans, DS, Forsen, T, Friedrich, N, Fumeron, F, Garcia, ME, Gartner, S, Han, BG, Havulinna, AS, Hayward, C, Hernandez, D, Hillege, H, Ittermann, T, Kent, JW, Kolcic, I, Laatikainen, T, Lahti, J, Leach, IM, Lee, CG, Lee, JY, Liu, T, Liu, YF, Lobbens, S, Loh, M, Lyytikainen, LP, Medina-Gomez, C, Michaelsson, K, Nalls, MA, Nielson, CM, Oozageer, L, Pascoe, L, Paternoster, L, Polasek, O, Ripatti, S, Sarzynski, MA, Shin, CS, Narancic, NS, Spira, D, Srikanth, P, Steinhagen-Thiessen, E, Sung, YJ, Swart, KMA, Taittonen, L, Tanaka, T, Tikkanen, E, van der Velde, Nathalie, Schoor, NM, Verweij, N (Niek), Wright, AF, Yu, L, Zmuda, JM, Eklund, N, Forrester, T, Grarup, N, Jackson, AU, Kristiansson, K, Kuulasmaa, T, Kuusisto, J, Lichtner, P, Luan, JA, Mahajan, A, Mannisto, S, Palmer, CD, Ried, JS, Scott, RA, Stancakova, A, Wagner, PJ, Demirkan, Ayse, Doring, A, Gudnason, V, Kiel, DP, Kuhnel, B, Mangino, M, McKnight, B, Menni, C, O'Connell, JR, Oostra, Ben, Shuldiner, AR, Song, KJ, Vandenput, L, Duijn, Cornelia, Vollenweider, P, White, CC, Boehnke, M, Boettcher, Y, Cooper, RS, Forouhi, NG, Gieger, C, Grallert, H, Hingorani, A, Jorgensen, T, Jousilahti, P, Kivimaki, M, Kumari, M, Laakso, M, Langenberg, C, Linneberg, A, Luke, A, McKenzie, CA, Palotie, A, Pedersen, O, Peters, A, Strauch, K, Tayo, BO, Wareham, NJ, Bennett, DA, Bertram, L, Blangero, J, Bluher, M, Bouchard, C, Campbell, H, Cho, NH, Cummings, SR, Czerwinski, SA, Demuth, I, Eckardt, R, Eriksson, JG, Ferrucci, L, Franco Duran, OH, Froguel, P, Gansevoort, RT, Hansen, T, Harris, TB, Hastie, N, Heliovaara, M, Hofman, Bert, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Knekt, PB, Koskinen, S, Kovacs, P, Lehtimaki, T, Lind, L, Liu, YM, Orwoll, ES, Osmond, C, Perola, M, Perusse, L, Raitakari, OT, Rankinen, T, Rao, DC, Rice, TK, Rivadeneira, Fernando, Rudan, I, Salomaa, V, Sorensen, TIA, Stumvoll, M, Tonjes, A, Towne, B, Tranah, GJ, Tremblay, A, Uitterlinden, André, van der Harst, P, Vartiainen, E, Viikari, JS, Vitart, V, Vohl, MC, Volzke, H, Walker, M, Wallaschofski, H, Wild, S, Wilson, JF, Yengo, L, Bishop, DT, Borecki, IB, Chambers, JC, Cupples, LA, Dehghan, Abbas, Deloukas, P, Fatemifar, G, Fox, C, Furey, TS, Franke, L, Han, JL, Hunter, DJ, Karjalainen, J, Karpe, F, Kaplan, RC, Kooner, JS, McCarthy, MI, Murabito, JM, Morris, AP, Bishop, JAN, North, KE, Ohlsson, C, Ong, KK, Prokopenko, I, Richards, JB, Schadt, EE, Spector, TD, Widen, E, Willer, CJ, Yang, Jiaqi, Ingelsson, E, Mohlke, KL, Hirschhorn, JN, Pospisilik, JA, Zillikens, M.C., Lindgren, C, Kilpelainen, TO, Loos, RJF, Lu, YC, Day, FR, Gustafsson, S, Buchkovich, ML, Na, JB, Bataille, V, Cousminer, DL, Dastani, Z, Drong, AW, Esko, T, Evans, DM, Falchi, M, Feitosa, MF, Ferreira, T, Hedman, AK, Haring, R, Hysi, PG, Iles, MM, Justice, AE, Kanoni, S, Lagou, V, Li, R, Li, X, Locke, A, Lu, C, Magi, R, Perry, JRB, Pers, TH, Qi, QB, Sanna, M, Schmidt, EM, Scott, WR, Shungin, D, Teumer, A, Vinkhuyzen, AAE, Walker, RW, Westra, HJ, Zhang, MF, Zhang, WH, Zhao, JH, Zhu, ZH, Afzal, U, Ahluwalia, TS, Bakker, SJL, Bellis, C, Bonnefond, A, Borodulin, K, Buchman, AS, Cederholm, T, Choh, AC, Choi, HJ, Curran, JE, de Groot, LCPGM (Lisette), De Jager, PL, Dhonukshe-Rutten, RAM, Enneman, Anke, Eury, E, Evans, DS, Forsen, T, Friedrich, N, Fumeron, F, Garcia, ME, Gartner, S, Han, BG, Havulinna, AS, Hayward, C, Hernandez, D, Hillege, H, Ittermann, T, Kent, JW, Kolcic, I, Laatikainen, T, Lahti, J, Leach, IM, Lee, CG, Lee, JY, Liu, T, Liu, YF, Lobbens, S, Loh, M, Lyytikainen, LP, Medina-Gomez, C, Michaelsson, K, Nalls, MA, Nielson, CM, Oozageer, L, Pascoe, L, Paternoster, L, Polasek, O, Ripatti, S, Sarzynski, MA, Shin, CS, Narancic, NS, Spira, D, Srikanth, P, Steinhagen-Thiessen, E, Sung, YJ, Swart, KMA, Taittonen, L, Tanaka, T, Tikkanen, E, van der Velde, Nathalie, Schoor, NM, Verweij, N (Niek), Wright, AF, Yu, L, Zmuda, JM, Eklund, N, Forrester, T, Grarup, N, Jackson, AU, Kristiansson, K, Kuulasmaa, T, Kuusisto, J, Lichtner, P, Luan, JA, Mahajan, A, Mannisto, S, Palmer, CD, Ried, JS, Scott, RA, Stancakova, A, Wagner, PJ, Demirkan, Ayse, Doring, A, Gudnason, V, Kiel, DP, Kuhnel, B, Mangino, M, McKnight, B, Menni, C, O'Connell, JR, Oostra, Ben, Shuldiner, AR, Song, KJ, Vandenput, L, Duijn, Cornelia, Vollenweider, P, White, CC, Boehnke, M, Boettcher, Y, Cooper, RS, Forouhi, NG, Gieger, C, Grallert, H, Hingorani, A, Jorgensen, T, Jousilahti, P, Kivimaki, M, Kumari, M, Laakso, M, Langenberg, C, Linneberg, A, Luke, A, McKenzie, CA, Palotie, A, Pedersen, O, Peters, A, Strauch, K, Tayo, BO, Wareham, NJ, Bennett, DA, Bertram, L, Blangero, J, Bluher, M, Bouchard, C, Campbell, H, Cho, NH, Cummings, SR, Czerwinski, SA, Demuth, I, Eckardt, R, Eriksson, JG, Ferrucci, L, Franco Duran, OH, Froguel, P, Gansevoort, RT, Hansen, T, Harris, TB, Hastie, N, Heliovaara, M, Hofman, Bert, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Knekt, PB, Koskinen, S, Kovacs, P, Lehtimaki, T, Lind, L, Liu, YM, Orwoll, ES, Osmond, C, Perola, M, Perusse, L, Raitakari, OT, Rankinen, T, Rao, DC, Rice, TK, Rivadeneira, Fernando, Rudan, I, Salomaa, V, Sorensen, TIA, Stumvoll, M, Tonjes, A, Towne, B, Tranah, GJ, Tremblay, A, Uitterlinden, André, van der Harst, P, Vartiainen, E, Viikari, JS, Vitart, V, Vohl, MC, Volzke, H, Walker, M, Wallaschofski, H, Wild, S, Wilson, JF, Yengo, L, Bishop, DT, Borecki, IB, Chambers, JC, Cupples, LA, Dehghan, Abbas, Deloukas, P, Fatemifar, G, Fox, C, Furey, TS, Franke, L, Han, JL, Hunter, DJ, Karjalainen, J, Karpe, F, Kaplan, RC, Kooner, JS, McCarthy, MI, Murabito, JM, Morris, AP, Bishop, JAN, North, KE, Ohlsson, C, Ong, KK, Prokopenko, I, Richards, JB, Schadt, EE, Spector, TD, Widen, E, Willer, CJ, Yang, Jiaqi, Ingelsson, E, Mohlke, KL, Hirschhorn, JN, Pospisilik, JA, Zillikens, M.C., Lindgren, C, Kilpelainen, TO, and Loos, RJF
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P < 5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Published: 2016

145. The Lin28/let-7 axis regulates glucose metabolism

Author: Zhu H, Shyh Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI, DIAGRAM Consortium, MAGIC Investigators, Altshuler D, Daley G.Q. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proença C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Boehnke M, McCarthy MI, Soranzo N, Wheeler E, Glazer NL, Bouatia Naji N, Mägi R, Randall J, Johnson T, Elliott P, Rybin D, Henneman P, Dehghan A, Hottenga JJ, Song K, Goel A, Egan JM, Lajunen T, Doney A, Voight BF, Kanoni S, Cavalcanti Proença C, Kumari M, Timpson NJ, Zabena C, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, Roccasecca RM, Pattou F, Sethupathy P, Ariyurek Y, Barter P, Beilby JP, Ben Shlomo Y, Bergmann S, Bochud M, Bonnefond A, Borch Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Crisponi L, Day IN, de Geus EJ, Delplanque J, Fedson AC, Fischer Rosinsky A, Forouhi NG, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Grundy S, Gwilliam R, Hallmans G, Hammond N, Han X, Hartikainen AL, Hayward C, Heath SC, Hercberg S, Hicks AA, Hillman DR, Hingorani AD, Hui J, Hung J, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Mahley R, Mangino M, Manning AK, Martínez Larrad MT, McAteer JB, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Mukherjee S, Naitza S, Neville MJ, Oostra BA, Orrù M, Pakyz R, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rice K, Ripatti S, Rivadeneira F, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Seedorf U, Sharp SJ, Shields B, Sigurðsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Tönjes A, Uitterlinden AG, van Dijk KW, Varma D, Visvikis Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Ward KL, Watkins H, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano Ríos M, Lind L, Palmer LJ, Franks PW, Ebrahim S, Marmot M, Wright AF, Stumvoll M, Hamsten A, Buchanan TA, Valle TT, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Ferrucci L, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Barroso I., PAOLISSO, Giuseppe, Zhu, H, Shyh Chang, N, Segrè, Av, Shinoda, G, Shah, Sp, Einhorn, W, Takeuchi, A, Engreitz, Jm, Hagan, Jp, Kharas, Mg, Urbach, A, Thornton, Je, Triboulet, R, Gregory, Ri, Diagram, Consortium, Magic, Investigator, Altshuler, D, Voight BF, Daley G. Q., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Couper, Dj, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, J, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Johnson, T, Elliott, P, Rybin, D, Henneman, P, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Egan, Jm, Lajunen, T, Voight, Bf, Kanoni, S, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Frants, R, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hicks, Aa, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Manning, Ak, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Oostra, Ba, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Perola, M, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Psaty, Bm, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sigurðsson, G, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tanaka, T, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Borecki, Ib, Loos, Rj, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Salomaa, V, Smith, Gd, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Dedoussis, Gv, Serrano Ríos, M, Lind, L, Palmer, Lj, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Buchanan, Ta, Valle, Tt, Rotter, Ji, Siscovick, D, Penninx, Bw, Boomsma, Di, Deloukas, P, Spector, Td, Ferrucci, L, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Waterworth, Dm, Vollenweider, P, Peltonen, L, Mooser, V, and Barroso, I.
Published: 2011

146. Interactions between genetic variants and breast cancer risk factors in thebreast and prostate cancer cohort consortium

Author: Campa D, Kaaks R, Le Marchand L, Haiman CA, Travis RC, Berg CD, Buring JE, Chanock SJ, Diver WR, Dostal L, Fournier A, Hankinson SE, Henderson BE, Hoover RN, Isaacs C, Johansson M, Kolonel LN, Kraft P, Lee IM, McCarty CA, Overvad K, Peeters PH, Riboli E, Sanchez MJ, Schumacher FR, Skeie G, Stram DO, Thun MJ, Trichopoulos D, Zhang S, Ziegler RG, Hunter DJ, Lindström S, Canzian F., PANICO, SALVATORE, Campa, D, Kaaks, R, Le Marchand, L, Haiman, Ca, Travis, Rc, Berg, Cd, Buring, Je, Chanock, Sj, Diver, Wr, Dostal, L, Fournier, A, Hankinson, Se, Henderson, Be, Hoover, Rn, Isaacs, C, Johansson, M, Kolonel, Ln, Kraft, P, Lee, Im, Mccarty, Ca, Overvad, K, Panico, Salvatore, Peeters, Ph, Riboli, E, Sanchez, Mj, Schumacher, Fr, Skeie, G, Stram, Do, Thun, Mj, Trichopoulos, D, Zhang, S, Ziegler, Rg, Hunter, Dj, Lindström, S, and Canzian, F.
Published: 2011

147. Response to Letter to the Editor entitled 'Comments on 'OARSI guidelines for the non-surgical management of knee osteoarthritis''

Author: McAlindon, TE, Bannuru, RR, Sullivan, MC, Arden, NK, Berenbaum, F, Bierma-Zeinstra, SM, Hawker, GA, Henrotin, Y, Hunter, DJ, Kawaguchi, H, Kwoh, K, Lohmander, S, Rannou, F, Roos, EM, Underwood, M, and General Practice
Subjects: medicine.medical_specialty, Consensus, Evidence-Based Medicine, Letter to the editor, business.industry, Biomedical Engineering, Alternative medicine, Evidence-based medicine, Osteoarthritis, Osteoarthritis, Knee, Patient-centered care, medicine.disease, body regions, Rheumatology, Patient-Centered Care, medicine, Physical therapy, Humans, Orthopedics and Sports Medicine, business
Published: 2014

148. Need to Know Review Number two: What Local Government Needs to Know about Public Health

Author: South, J, Hunter, DJ, and Gamsu, M
Abstract: This review of existing research on local government and public health focuses on the leadership role of local government in developing local public health systems that are capable of addressing the wider determinants of health.
Published: 2014

149. Genome-wide association study identifies multiple loci associated with bladder cancer risk

Author: Figueroa, JD, Ye, Y, Siddiq, A, Garcia-Closas, M, Chatterjee, N, Prokunina-Olsson, L, Cortessis, VK, Kooperberg, C, Cussenot, O, Benhamou, S, Prescott, J, Porru, S, Dinney, CP, Malats, N, Baris, D, Purdue, M, Jacobs, EJ, Albanes, D, Wang, Z, Deng, X, Chung, CC, Tang, W, Bueno-De-Mesquita, HB, Trichopoulos, D, Ljungberg, B, Clavel-Chapelon, F, Weiderpass, E, Krogh, V, Dorronsoro, M, Travis, R, Tjonneland, A, Brenan, P, Chang-Claude, J, Riboli, E, Conti, D, Gago Dominguez, Manuela, Stern, MC, Pike, MC, Van den Berg, D, Yuan, JM, Hohensee, C, Rodabough, R, Cancel-Tassin, G, Roupret, M, Comperat, E, Chen, C, De Vivo, I, Giovannucci, E, Hunter, DJ, Kraft, P, Lindstrom, S, Carta, A, Pavanello, S, Arici, C, Mastrangelo, G, Kamat, AM, Lerner, SP, Grossman, HB, Lin, J, Gu, J, Pu, X, Hutchinson, A, Burdette, L, Wheeler, W, Kogevinas, M, Tardon, A, Serra, C, Carrato, A, Garcia-Closas, R, Lloreta, J, Schwenn, M, Karagas, MR, Johnson, A, Schned, A, Armenti, KR, Hosain, GM, Andriole, G, Grubb, R, Black, A, Diver, WR, Gapstur, SM, Weinstein, SJ, Virtamo, J, Haiman, CA, Landi, MT, Caporaso, N, Fraumeni, JF, Vineis, P, Wu, X, Silverman, DT, Chanock, S, and Rothman, N
Subjects: Risk, Genotype, Meta-Analysis as Topic, Urinary Bladder Neoplasms, Genetic Loci, Case-Control Studies, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Genome-Wide Association Study
Abstract: Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 x 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 x 10(-9)) and rs907611 on 11p15.5 (P = 4.11 x 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 x 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 x 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
Published: 2014

150. Health system transformation: engaging professions to make it happen

Author: Hunter, DJ, primary
Published: 2016
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