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1. A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

Author: van Zuydam, Natalie R, Ahlqvist, Emma, Sandholm, Niina, Deshmukh, Harshal, Rayner, N William, Abdalla, Moustafa, Ladenvall, Claes, Ziemek, Daniel, Fauman, Eric, Robertson, Neil R, McKeigue, Paul M, Valo, Erkka, Forsblom, Carol, Harjutsalo, Valma, Perna, Annalisa, Rurali, Erica, Marcovecchio, M Loredana, Igo, Robert P, Salem, Rany M, Perico, Norberto, Lajer, Maria, Käräjämäki, Annemari, Imamura, Minako, Kubo, Michiaki, Takahashi, Atsushi, Sim, Xueling, Liu, Jianjun, van Dam, Rob M, Jiang, Guozhi, Tam, Claudia HT, Luk, Andrea OY, Lee, Heung Man, Lim, Cadmon KP, Szeto, Cheuk Chun, So, Wing Yee, Chan, Juliana CN, Ang, Su Fen, Dorajoo, Rajkumar, Wang, Ling, Clara, Tan Si Hua, McKnight, Amy-Jayne, Duffy, Seamus, Pezzolesi, Marcus G, Marre, Michel, Gyorgy, Beata, Hadjadj, Samy, Hiraki, Linda T, Ahluwalia, Tarunveer S, Almgren, Peter, Schulz, Christina-Alexandra, Orho-Melander, Marju, Linneberg, Allan, Christensen, Cramer, Witte, Daniel R, Grarup, Niels, Brandslund, Ivan, Melander, Olle, Paterson, Andrew D, Tregouet, David, Maxwell, Alexander P, Lim, Su Chi, Ma, Ronald CW, Tai, E Shyong, Maeda, Shiro, Lyssenko, Valeriya, Tuomi, Tiinamaija, Krolewski, Andrzej S, Rich, Stephen S, Hirschhorn, Joel N, Florez, Jose C, Dunger, David, Pedersen, Oluf, Hansen, Torben, Rossing, Peter, Remuzzi, Giuseppe, Brosnan, Mary Julia, Palmer, Colin NA, Groop, Per-Henrik, Colhoun, Helen M, Groop, Leif C, McCarthy, Mark I, Koivula, S, Uggeldahl, T, Forslund, T, Halonen, A, Koistinen, A, Koskiaho, P, Laukkanen, M, Saltevo, J, Tiihonen, M, Forsen, M, Granlund, H, Jonsson, A-C, Nyroos, B, Kinnunen, P, Orvola, A, Salonen, T, Vähänen, A, Paldanius, Kotka R, and Riihelä, M
Subjects: Diabetes, Genetics, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Adult, Aged, Aged, 80 and over, Case-Control Studies, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney Failure, Chronic, Male, Middle Aged, Polymorphism, Single Nucleotide, Renal Insufficiency, Chronic, Finnish Diabetic Nephropathy Study, Hong Kong Diabetes Registry Theme-based Research Scheme Project Group, Warren 3 and Genetics of Kidneys in Diabetes (GoKinD) Study Group, GENIE (GEnetics of Nephropathy an International Effort) Consortium, Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, SUrrogate markers for Micro- and Macrovascular hard endpoints for Innovative diabetes Tools (SUMMIT) Consortium, Medical and Health Sciences, Endocrinology & Metabolism
Abstract: Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.
Published: 2018

2. No correlation between carotid intima-media thickness and long-term glycemic control in individuals with type 1 diabetes.

Author: Inkeri, Jussi, Harjutsalo, Valma, Martola, Juha, Putaala, Jukka, Groop, Per-Henrik, Gordin, Daniel, Thorn, Lena M., Koivula, S., Uggeldahl, T., Forslund, T., Halonen, A., Koistinen, A., Koskiaho, P., Laukkanen, M., Saltevo, J., Tiihonen, M., Forsen, SM., Granlund, H., Jonsson, A.-C., and Nyroos, B.
Subjects: CAROTID intima-media thickness, TYPE 1 diabetes, GLYCEMIC control, GLYCOSYLATED hemoglobin, CAROTID artery ultrasonography, HYPERGLYCEMIA, BLOOD sugar, INSULIN
Abstract: Aims: To determine whether carotid intima-media thickness (CIMT), a surrogate marker of cardiovascular disease (CVD), is associated with long-term blood glucose control in individuals with type 1 diabetes (T1D). Methods: We recruited 508 individuals (43.4% men; median age 46.1, IQR 37.8–55.9 years) with T1D (median diabetes duration of 30.4, IQR 21.2–40.8 years) in a cross-sectional retrospective sub-study, part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Glycated hemoglobin (HbA1c) data were collected retrospectively over the course of ten years (HbA1c-meanoverall) prior to the clinical study visit that included a clinical examination, biochemical sampling, and ultrasound of the common carotid arteries. Results: Individuals with T1D had a median CIMT of 606 μm (IQR 538–683 μm) and HbA1c of 8.0% (7.3–8.8%) during the study visit and HbA1c-meanoverall of 8.0% (IQR 7.3–8.8%). CIMT did not correlate with HbA1c (p = 0.228) at visit or HbA1c-meanoverall (p = 0.063). After controlling for relevant factors in multivariable linear regression analysis, only age was associated with CIMT (p < 0.001). After further dividing CIMT into quartiles, no correlation between long-term glucose control and CIMT (%, 1st 8.1 [IQR 7.2–8.9] vs 4th 7.9 [7.4–8.7], p = 0.730) was found. Conclusions: We observed no correlation between long-term blood glucose control and CIMT in individuals with T1D. This finding suggests that the development of early signs of macrovascular atherosclerosis is not strongly affected by the glycemic control in people with T1D. [ABSTRACT FROM AUTHOR]
Published: 2024
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3. Diabeteksen kansallisen ehkäisyhankkeen pitkäaikaiset vaikutukset ja merkitys

Author: Uusitupa, M. (Matti), Saaristo, T. (Timo), Rintamäki, R. (Reeta), Pölönen, A. (Auli), Valtanen, M. (Mikko), Rautio, N. (Nina), Risku, S. (Sari), Länsipuro, L. (Liisa), Hirsso, P. (Päivi), Ahtiainen, P. (Petteri), Saltevo, J. (Juha), Keinänen- Kiukaanniemi, S. (Sirkka), Moilanen, L. (Leena), Lindström, J. (Jaana), Peltonen, M. (Markku), Oksa, H. (Heikki), Tuomilehto, J. (Jaakko), Uusitupa, M. (Matti), Saaristo, T. (Timo), Rintamäki, R. (Reeta), Pölönen, A. (Auli), Valtanen, M. (Mikko), Rautio, N. (Nina), Risku, S. (Sari), Länsipuro, L. (Liisa), Hirsso, P. (Päivi), Ahtiainen, P. (Petteri), Saltevo, J. (Juha), Keinänen- Kiukaanniemi, S. (Sirkka), Moilanen, L. (Leena), Lindström, J. (Jaana), Peltonen, M. (Markku), Oksa, H. (Heikki), and Tuomilehto, J. (Jaakko)
Abstract: Tiivistelmä Tyypin 2 diabeteksen ilmaantuvuus perustuen erityiskorvattavien lääkkeiden käyttöön on laskenut Suomessa koko 2010-luvun, mutta D2D-alueen sairaanhoitopiirien väliset erot ovat säilyneet. Kolmasosa D2D-hankkeessa vuosina 2003–2007 tunnistetuista suuren sairastumisriskin henkilöistä osallistui tarjottuun hoito- ja seurantaohjelmaan. Perusterveydenhuollossa ja myös työterveyshuollossa on herätty torjumaan diabetesta. Väestön diabetestietoisuus on lisääntynyt koko maassa DEHKO-ohjelman, D2D-hankkeen ja FINDRISC-diabeteksen riskitestin laajan käytön myötä. Tuloksellinen tyypin 2 diabeteksen ehkäisy edellyttää sekä korkean riskin että väestötason strategiaan perustuvia toimia ja monialaista yhteistyötä terveyttä edistävien elintapojen edistämiseksi ja omaksumiseksi.
Published: 2023

4. Frequent pain in older people with and without diabetes – Finnish community based study

Author: Karjalainen, M., Saltevo, J., Tiihonen, M., Haanpää, M., Kautiainen, H., and Mäntyselkä, P.
Published: 2018
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5. Long-term outcomes of lifestyle intervention to prevent type 2 diabetes in people at high risk in primary health care

Author: Rintamäki, R. (Reeta), Rautio, N. (Nina), Peltonen, M. (Markku), Jokelainen, J. (Jari), Keinänen-Kiukaanniemi, S. (Sirkka), Oksa, H. (Heikki), Saaristo, T. (Timo), Puolijoki, H. (Hannu), Saltevo, J. (Juha), Tuomilehto, J. (Jaakko), Uusitupa, M. (Matti), Moilanen, L. (Leena), Rintamäki, R. (Reeta), Rautio, N. (Nina), Peltonen, M. (Markku), Jokelainen, J. (Jari), Keinänen-Kiukaanniemi, S. (Sirkka), Oksa, H. (Heikki), Saaristo, T. (Timo), Puolijoki, H. (Hannu), Saltevo, J. (Juha), Tuomilehto, J. (Jaakko), Uusitupa, M. (Matti), and Moilanen, L. (Leena)
Abstract: Aims: The Finnish National Diabetes Prevention Program (FIN-D2D) was the first large-scale diabetes prevention program in a primary health care setting in the world. The risk reduction of type 2 diabetes was 69% after one-year intervention in high-risk individuals who were able to lose 5% of their weight. We investigated long-term effects of one-year weight change on the incidence of type 2 diabetes, cardiovascular events, and all-cause mortality. Methods: A total of 10,149 high-risk individuals for type 2 diabetes were identified in primary health care centers and they were offered lifestyle intervention to prevent diabetes. Of these individuals who participated in the baseline screening, 8353 had an oral glucose tolerance test (OGTT). Complete follow-up data during one-year intervention were available for 2730 individuals and those were included in the follow-up analysis. The long-term outcome events were collected from national health registers after the median follow-up of 7.4 years. Results: Among individuals who lost weight 2.5−4.9% and 5% or more during the first year, the hazard ratio for the incidence of drug-treated diabetes was 0.63 (95% CI 0.49−0.81, p = 0.0001), and 0.71 (95% CI 0.56−0.90, p = 0.004), respectively, compared with those with stable weight. There were no significant differences in cardiovascular events or all-cause mortality among study participants according to one-year weight changes. Conclusions: High-risk individuals for type 2 diabetes who achieved a moderate weight loss by one-year lifestyle counseling in primary health care had a long-term reduction in the incidence of drug-treated type 2 diabetes. The observed moderate weight loss was not associated with a reduction in cardiovascular events.
Published: 2021

6. Factors predicting 31-year survival among a population cohort in Northern Finland

Author: Perkkiö, Y. (Yrjö), Auvinen, J. (Juha), Timonen, M. (Markku), Jokelainen, J. (Jari), Valkeapää, N. (Nihkolas), Koiranen, M. (Markku), Saltevo, J. (Juha), Keinänen-Kiukaanniemi, S. (Sirkka), Perkkiö, Y. (Yrjö), Auvinen, J. (Juha), Timonen, M. (Markku), Jokelainen, J. (Jari), Valkeapää, N. (Nihkolas), Koiranen, M. (Markku), Saltevo, J. (Juha), and Keinänen-Kiukaanniemi, S. (Sirkka)
Abstract: We evaluated the survival of a subarctic population and the significance of traditional risk factors for mortality, causes of death and their seasonal variation from the period of 1984–2014. By the end of 2014 (follow-up), 644 (34.4% from 1,869) participants had died (42.1% of cardiovascular causes, 22.4% of neoplastic diseases). The average age at death±SD was 74.6±11.4 years for women (n=284) and 70.2±12.0 years for men (n=360). After adjusting for baseline age, the major risk factors predicting death were male sex (hazard ratio [HR] 1.80; 95% confidence interval [CI] 1.54–2.10), current smoking (HR 1.85; 95% CI 1.58–2.17), obesity (HR 1.75; 95% CI 1.45–2.12), high blood pressure (HR 1.46; 95% CI 1.24–1.72), cardiovascular disease (HR 1.62; 95% CI 1.36–1.93) and depression (HR 1.61; 95% CI 1.21–2.14) at baseline. The most common causes of death and the main risk factors predicting death in this population were the same as reported globally. Lifestyle factors had an important impact in predicting survival. The most common causes of death were the same for men and women. There was no significant difference in overall mortality rate between winter and summer, but cerebrovascular and pulmonary causes of death were more common during winter.
Published: 2021

7. Troglitazone reduces hyperglycaemia and selectively acute-phase serum proteins in patients with Type II diabetes

Author: Ebeling, P., Teppo, A. -M., Koistinen, H. A., Viikari, J., Rönnemaa, T., Nissén, M., Bergkulla, S., Salmela, P., Saltevo, J., and Koivisto, V. A.
Published: 1999
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8. Nateglinide combination therapy with basal insulin and metformin in patients with Type 2 diabetes

Author: Juurinen, L., Tiikkainen, M., Saltevo, J., Nikkilä, K., Lanki, H., Leppävuori, E., Kock, T., Teikari-Myyrä, T., Kauppinen-Mäkelin, R., Kotronen, A., and Yki-Järvinen, H.
Published: 2009
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9. Levels of adiponectin, C-reactive protein and interleukin-1 receptor antagonist are associated with insulin sensitivity: a population-based study

Author: Saltevo, J., Laakso, M., Jokelainen, J., Keinänen-Kiukaanniemi, S., Kumpusalo, E., and Vanhala, M.
Published: 2008
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10. Gender differences in C-reactive protein, interleukin-1 receptor antagonist and adiponectin levels in the metabolic syndrome: a population-based study

Author: Saltevo, J., Vanhala, M., Kautiainen, H., Kumpusalo, E., and Laakso, M.
Published: 2008

11. Implementation of the National Type 2 Diabetes Prevention Programme in Finland: FIN-D2D: A110

Author: Saaristo, T, Peltonen, M, Keinänen-Kiukaanniemi, S, Vanhala, M, Saltevo, J, Oksa, H, Korpi-Hyövälti, E, and Tuomilehto, J
Published: 2006

12. Glucose status and depressive symptoms:a cohort study of elderly people in northwest Finland

Author: Perkkiö, Y. (Yrjö), Jokelainen, J. (Jari), Auvinen, J. (Juha), Eskola, P. (Pasi), Saltevo, J. (Juha), Keinänen-Kiukaanniemi, S. (Sirkka), Timonen, M. (Markku), Perkkiö, Y. (Yrjö), Jokelainen, J. (Jari), Auvinen, J. (Juha), Eskola, P. (Pasi), Saltevo, J. (Juha), Keinänen-Kiukaanniemi, S. (Sirkka), and Timonen, M. (Markku)
Abstract: Objective: To assess the association between depressive symptoms and impaired glucose metabolism in the elderly population in arctic latitudes. Design: A population-based study. Setting. Community. Subjects: The study population consisted of 1,830 subjects born between the years 1915 and 1958 in the northernmost part of Finland, the Muonio-Enontekiö district, who participated in a health survey during 1974–1984. In 2014, a health questionnaire was sent to 1,037 subjects, and 757 participants (73%) answered it. Those (n = 629) living in the Muonio-Enontekiö district undergone a clinical examination in 2014 and 2015 including blood collections. Main outcome measures: Depressive symptoms defined by the Beck Depression Inventory II (BDI II) with a cut-off point of 14. Different diabetic states based on WHO’s classification criteria defined by fasting plasma glucose and ADA’s criteria by glycosylated haemoglobin (HbA1c) values. Results: According to logistic regression analysis, depressive symptoms (BDI-II ≥ 14) were associated statistically significantly with previously known type 2 diabetes, the odds ratio (OR) being 4.33 (95% CI 1.53–14.14). Regarding prediabetic fasting glucose/HbA1c values, the corresponding OR was 2.94 (95% CI 1.17–8.94). The prevalence of depressive symptoms (BDI-II ≥ 14) was 7.1%, (men 9.7% and women 5.4%) and 13.7% (men 9.9% and women 17.0%) in subjects living in Muonio-Enontekiö district and in those who had moved away from there, respectively. Conclusions: The association of depressive symptoms between prediabetes and diabetes seems to be present also in the northernmost latitudes of the world.
Published: 2019

13. Finnish Current Care Guideline for Diabetes: interactive approach to improve individualised treatment

Author: Virkamäki, A. and Saltevo, J.
Published: 2011
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14. Single-nucleotide polymorphisms may cause erroneous results in primer-introduced restriction enzyme analyses:a case of molecular misdiagnosis of homozygous vs heterozygous familial hypercholesterolemia

Author: Vuorio, AF, Paulin, L, Saltevo, J, and Kontula, K
Published: 1999
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15. Gender differences in thyroid function and obesity among finnish women and men:the FIN-D2D-study

Author: Saltevo, J. (Juha), Kautiainen, H. (Hannu), Mäntyselkä, P. (Pekka), Jula, A. (Antti), Keinänen-Kiukaanniemi, S. (Sirkka), Korpi-Hyövälti, E. (Eeva), Niskanen, L. (Leo), Oksa, H. (Heikki), Saaristo, T. (Timo), and Vanhala, M. (Mauno)
Subjects: body weight, obesity, thyroid function, gender difference, Finnish population
Abstract: Background: Our aim was to study the relationship between thyroid function and body weight in a large Finnish adult population, taking into account the effect of gender, because the results of previous studies are conflicting. Methods: A random sample of 4500 Finnish subjects aged 45–74 years old was selected from the National Population Register. The participation rate was 64%. Height, weight, waist circumference, and blood pressure were measured. Medications used, current smoking, the use of alcohol, and leisure-time physical activity (LTPA) wereas queried. Thyroid values (free T4, free T3, and TSH) were measured in 1307 men and 1434 women. Subjects receiving thyroid hormone (N=92) were excluded. Results: The mean age of the subjects was 59.7 years and their mean body mass index (BMI) was 27.4 kg/m². After adjustment for age, LTPA, and current smoking, TSH showed no linearity (p=0.09) across increasing BMI; in women TSH ranged from 1.85 ± 1.15 to 2.02 ± 1.29 IU/L and in men, from 1.79 ± 1.19 to 2.04 ± 1.33 IU/L (p=0.13). FT3 -values increased from 3.85 ± 0.67 to 3.97 ± 0.59 pmol/L in women (p=0.004), but not in men, with increasing BMI. FT4 -values decreased from 13.78 ± 2.07 to 13.31 ± 1.91 pmol/L with increasing BMI in men (p
Published: 2016

16. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Ehret, G.B. Ferreira, T. Chasman, D.I. Jackson, A.U. Schmidt, E.M. Johnson, T. Thorleifsson, G. Luan, J. Donnelly, L.A. Kanoni, S. Petersen, A.-K. Pihur, V. Strawbridge, R.J. Shungin, D. Hughes, M.F. Meirelles, O. Kaakinen, M. Bouatia-Naji, N. Kristiansson, K. Shah, S. Kleber, M.E. Guo, X. Lyytikäinen, L.-P. Fava, C. Eriksson, N. Nolte, I.M. Magnusson, P.K. Salfati, E.L. Rallidis, L.S. Theusch, E. Smith, A.J.P. Folkersen, L. Witkowska, K. Pers, T.H. Joehanes, R. Kim, S.K. Lataniotis, L. Jansen, R. Johnson, A.D. Warren, H. Kim, Y.J. Zhao, W. Wu, Y. Tayo, B.O. Bochud, M. Absher, D. Adair, L.S. Amin, N. Arking, D.E. Axelsson, T. Baldassarre, D. Balkau, B. Bandinelli, S. Barnes, M.R. Barroso, I. Bevan, S. Bis, J.C. Bjornsdottir, G. Boehnke, M. Boerwinkle, E. Bonnycastle, L.L. Boomsma, D.I. Bornstein, S.R. Brown, M.J. Burnier, M. Cabrera, C.P. Chambers, J.C. Chang, I.-S. Cheng, C.-Y. Chines, P.S. Chung, R.-H. Collins, F.S. Connell, J.M. Döring, A. Dallongeville, J. Danesh, J. De Faire, U. Delgado, G. Dominiczak, A.F. Doney, A.S.F. Drenos, F. Edkins, S. Eicher, J.D. Elosua, R. Enroth, S. Erdmann, J. Eriksson, P. Esko, T. Evangelou, E. Evans, A. Fall, T. Farrall, M. Felix, J.F. Ferrières, J. Ferrucci, L. Fornage, M. Forrester, T. Franceschini, N. Franco, O.H. Franco-Cereceda, A. Fraser, R.M. Ganesh, S.K. Gao, H. Gertow, K. Gianfagna, F. Gigante, B. Giulianini, F. Goel, A. Goodall, A.H. Goodarzi, M.O. Gorski, M. Gräßler, J. Groves, C.J. Gudnason, V. Gyllensten, U. Hallmans, G. Hartikainen, A.-L. Hassinen, M. Havulinna, A.S. Hayward, C. Hercberg, S. Herzig, K.-H. Hicks, A.A. Hingorani, A.D. Hirschhorn, J.N. Hofman, A. Holmen, J. Holmen, O.L. Hottenga, J.-J. Howard, P. Hsiung, C.A. Hunt, S.C. Ikram, M.A. Illig, T. Iribarren, C. Jensen, R.A. Kähönen, M. Kang, H.M. Kathiresan, S. Keating, B.J. Khaw, K.-T. Kim, Y.K. Kim, E. Kivimaki, M. Klopp, N. Kolovou, G. Komulainen, P. Kooner, J.S. Kosova, G. Krauss, R.M. Kuh, D. Kutalik, Z. Kuusisto, J. Kvaløy, K. Lakka, T.A. Lee, N.R. Lee, I.-T. Lee, W.-J. Levy, D. Li, X. Liang, K.-W. Lin, H. Lin, L. Lindström, J. Lobbens, S. Männistö, S. Müller, G. Müller-Nurasyid, M. Mach, F. Markus, H.S. Marouli, E. McCarthy, M.I. McKenzie, C.A. Meneton, P. Menni, C. Metspalu, A. Mijatovic, V. Moilanen, L. Montasser, M.E. Morris, A.D. Morrison, A.C. Mulas, A. Nagaraja, R. Narisu, N. Nikus, K. O'Donnell, C.J. O'Reilly, P.F. Ong, K.K. Paccaud, F. Palmer, C.D. Parsa, A. Pedersen, N.L. Penninx, B.W. Perola, M. Peters, A. Poulter, N. Pramstaller, P.P. Psaty, B.M. Quertermous, T. Rao, D.C. Rasheed, A. Rayner, N.W. Renström, F. Rettig, R. Rice, K.M. Roberts, R. Rose, L.M. Rossouw, J. Samani, N.J. Sanna, S. Saramies, J. Schunkert, H. Sebert, S. Sheu, W.H.-H. Shin, Y.-A. Sim, X. Smit, J.H. Smith, A.V. Sosa, M.X. Spector, T.D. Stančáková, A. Stanton, A.V. Stirrups, K.E. Stringham, H.M. Sundstrom, J. Swift, A.J. Syvänen, A.-C. Tai, E.-S. Tanaka, T. Tarasov, K.V. Teumer, A. Thorsteinsdottir, U. Tobin, M.D. Tremoli, E. Uitterlinden, A.G. Uusitupa, M. Vaez, A. Vaidya, D. Van Duijn, C.M. Van Iperen, E.P.A. Vasan, R.S. Verwoert, G.C. Virtamo, J. Vitart, V. Voight, B.F. Vollenweider, P. Wagner, A. Wain, L.V. Wareham, N.J. Watkins, H. Weder, A.B. Westra, H.-J. Wilks, R. Wilsgaard, T. Wilson, J.F. Wong, T.Y. Yang, T.-P. Yao, J. Yengo, L. Zhang, W. Zhao, J.H. Zhu, X. Bovet, P. Cooper, R.S. Mohlke, K.L. Saleheen, D. Lee, J.-Y. Elliott, P. Gierman, H.J. Willer, C.J. Franke, L. Hovingh, G.K. Taylor, K.D. Dedoussis, G. Sever, P. Wong, A. Lind, L. Assimes, T.L. Njølstad, I. Schwarz, P.E.H. Langenberg, C. Snieder, H. Caulfield, M.J. Melander, O. Laakso, M. Saltevo, J. Rauramaa, R. Tuomilehto, J. Ingelsson, E. Lehtimäki, T. Hveem, K. Palmas, W. März, W. Kumari, M. Salomaa, V. Chen, Y.-D.I. Rotter, J.I. Froguel, P. Jarvelin, M.-R. Lakatta, E.G. Kuulasmaa, K. Franks, P.W. Hamsten, A. Wichmann, H.-E. Palmer, C.N.A. Stefansson, K. Ridker, P.M. Loos, R.J.F. Chakravarti, A. Deloukas, P. Morris, A.P. Newton-Cheh, C. Munroe, P.B.
Abstract: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation. © 2016 Nature America, Inc. All rights reserved.
Published: 2016

17. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Ehret, G.B. (Georg), Ferreira, T. (Teresa), Chasman, D.I. (Daniel), Jackson, A.U. (Anne), Schmidt, E.M. (Ellen), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'An), Donnelly, L.A. (Louise), Kanoni, S. (Stavroula), Petersen, A.K., Pihur, V. (Vasyl), Strawbridge, R.J. (Rona), Shungin, D. (Dmitry), Hughes, M.F. (Maria F.), Meirelles, O., Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Lyytikäinen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Niclas), Nolte, I.M. (Ilja), Magnusson, P.K. (Patrik), Salfati, E. (Elias), Rallidis, L.S. (Loukianos), Theusch, E. (Elizabeth), Smith, A.J. (Andrew), Folkersen, L. (Lasse), Witkowska, H.E. (Ewa), Pers, T.H. (Tune), Joehanes, R. (Roby), Kim, S.K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R., Johnson, A.D. (Andrew), Warren, H. (Helen), Kim, Y.J., Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. (Bamidele), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L.S. (Linda), Amin, N. (Najaf), Arking, D.E. (Dan), Axelsson, T. (Tomas), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M.J. (Michael), Barroso, I.E. (Inês), Bevan, S. (Stephen), Bis, J.C. (Joshua), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Burnier, M. (Michel), Cabrera, C.P. (Claudia P.), Chambers, J.C. (John), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P.S. (Peter), Chung, R.-H. (Ren-Hua), Collins, F.S. (Francis), Connell, J.M. (John M.), Döring, A. (Angela), Dallongeville, J., Danesh, J. (John), Faire, U. (Ulf) de, Delgado, G., Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Drenos, F. (Fotios), Edkins, T. (Ted), Eicher, J.D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tõnu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fall, M. (Magnus), Farrall, M. (Martin), Felix, J.F. (Janine), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschini, N. (Nora), Franco, O.H. (Oscar), Franco-Cereceda, A. (Anders), Fraser, R.M. (Ross), Ganesh, S.K. (Santhi), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goel, A. (Anuj), Goodall, A.H. (Alison), Goodarzi, M. (Mark), Gorski, M. (Mathias), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Göran), Hartikainen, A.L., Hassinen, M. (Maija), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.H., Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holmen, J. (Jostein), Holmen, O.L. (Oddgeir), Hottenga, J.J. (Jouke Jan), Howard, P. (Philip), Hsiung, C.A. (Chao A.), Hunt, S.C. (Steven), Ikram, M.K. (Kamran), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R.A. (Richard A.), Kähönen, M. (Mika), Kang, H.M. (Hyun Min), Kathiresan, S. (Sekar), Keating, J. (John), Khaw, K.T., Kim, Y.K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J.S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R.M. (Ronald), Kuh, D. (Diana), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Lee, N.R. (Nanette), Lee, I.T., Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Männistö, S. (Satu), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), MacH, F. (François), Markus, H.S. (Hugh), Marouli, E. (Eirini), McCarthy, M.I. (Mark), McKenzie, C.A. (Colin), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M.E. (May E.), Morris, A.D. (Andrew), Morrison, A.C. (Alanna), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), O'Reilly, P.F. (Paul), Ong, K.K. (Ken), Paccaud, F. (Fred), Palmer, C. (Cameron), Parsa, A. (Afshin), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rao, D.C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Roberts, R. (Robert), Rose, L.M. (Lynda), Rossouw, J. (Jacques), Samani, N.J. (Nilesh), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W.H.-H. (Wayne H.-H.), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smith, A.V. (Davey), Smith, A.V. (Albert Vernon), Sosa, M.X. (Maria X.), Spector, T.D. (Timothy), Stancáková, A. (Alena), Stanton, A. (Alice), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swift, A.J. (Amy), Syvänen, A.C., Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K.V. (Kirill), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M.D. (Martin), Tremoli, E. (Elena), Uitterlinden, A.G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), Van Duijn, C.M. (Cornelia M.), Iperen, E.P.A. (Erik) van, Vasan, R.S. (Ramachandran S.), Verwoert, G.C. (Germaine), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B.F. (Benjamin), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L.V. (Louise V.), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weder, A.B. (Alan), Westra, H.J. (Harm-Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J.F. (James F.), Wong, T.Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jiefen), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R.S. (Richard S.), Mohlke, K.L. (Karen), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, L.M. (Lobke), Willer, C.J. (Cristen), Franke, L. (Lude), Hovingh, G.K. (Kees), Taylor, K.D. (Kent), Dedoussis, G.V. (George), Sever, P. (Peter), Wong, A. (Andrew), Kao, W.H.L. (Wen), Assimes, T.L. (Themistocles), Njølstad, I. (Inger), Schwarz, P.E.H. (Peter), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. (Mark), Melander, O. (Olle), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), März, W. (Winfried), Kumari, M. (Meena), Salomaa, V. (Veikko), Chen, Y.D. (Y.), Rotter, J.I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. (Edward), Kuulasmaa, K. (Kari), Franks, P.W. (Paul), Hamsten, A. (Anders), Wichmann, H.E. (Heinz Erich), Palmer, C.N.A. (Colin), Stefansson, K. (Kari), Ridker, P.M. (Paul), Loos, R.J.F. (Ruth), Chakravarti, A. (Aravinda), Deloukas, P. (Panagiotis), Morris, A.P. (Andrew), Newton-Cheh, C. (C.), Munroe, P. (Patricia), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Chasman, D.I. (Daniel), Jackson, A.U. (Anne), Schmidt, E.M. (Ellen), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'An), Donnelly, L.A. (Louise), Kanoni, S. (Stavroula), Petersen, A.K., Pihur, V. (Vasyl), Strawbridge, R.J. (Rona), Shungin, D. (Dmitry), Hughes, M.F. (Maria F.), Meirelles, O., Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Lyytikäinen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Niclas), Nolte, I.M. (Ilja), Magnusson, P.K. (Patrik), Salfati, E. (Elias), Rallidis, L.S. (Loukianos), Theusch, E. (Elizabeth), Smith, A.J. (Andrew), Folkersen, L. (Lasse), Witkowska, H.E. (Ewa), Pers, T.H. (Tune), Joehanes, R. (Roby), Kim, S.K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R., Johnson, A.D. (Andrew), Warren, H. (Helen), Kim, Y.J., Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. (Bamidele), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L.S. (Linda), Amin, N. (Najaf), Arking, D.E. (Dan), Axelsson, T. (Tomas), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M.J. (Michael), Barroso, I.E. (Inês), Bevan, S. (Stephen), Bis, J.C. (Joshua), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Burnier, M. (Michel), Cabrera, C.P. (Claudia P.), Chambers, J.C. (John), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P.S. (Peter), Chung, R.-H. (Ren-Hua), Collins, F.S. (Francis), Connell, J.M. (John M.), Döring, A. (Angela), Dallongeville, J., Danesh, J. (John), Faire, U. (Ulf) de, Delgado, G., Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Drenos, F. (Fotios), Edkins, T. (Ted), Eicher, J.D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tõnu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fall, M. (Magnus), Farrall, M. (Martin), Felix, J.F. (Janine), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschini, N. (Nora), Franco, O.H. (Oscar), Franco-Cereceda, A. (Anders), Fraser, R.M. (Ross), Ganesh, S.K. (Santhi), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goel, A. (Anuj), Goodall, A.H. (Alison), Goodarzi, M. (Mark), Gorski, M. (Mathias), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Göran), Hartikainen, A.L., Hassinen, M. (Maija), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.H., Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holmen, J. (Jostein), Holmen, O.L. (Oddgeir), Hottenga, J.J. (Jouke Jan), Howard, P. (Philip), Hsiung, C.A. (Chao A.), Hunt, S.C. (Steven), Ikram, M.K. (Kamran), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R.A. (Richard A.), Kähönen, M. (Mika), Kang, H.M. (Hyun Min), Kathiresan, S. (Sekar), Keating, J. (John), Khaw, K.T., Kim, Y.K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J.S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R.M. (Ronald), Kuh, D. (Diana), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Lee, N.R. (Nanette), Lee, I.T., Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Männistö, S. (Satu), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), MacH, F. (François), Markus, H.S. (Hugh), Marouli, E. (Eirini), McCarthy, M.I. (Mark), McKenzie, C.A. (Colin), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M.E. (May E.), Morris, A.D. (Andrew), Morrison, A.C. (Alanna), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), O'Reilly, P.F. (Paul), Ong, K.K. (Ken), Paccaud, F. (Fred), Palmer, C. (Cameron), Parsa, A. (Afshin), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rao, D.C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Roberts, R. (Robert), Rose, L.M. (Lynda), Rossouw, J. (Jacques), Samani, N.J. (Nilesh), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W.H.-H. (Wayne H.-H.), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smith, A.V. (Davey), Smith, A.V. (Albert Vernon), Sosa, M.X. (Maria X.), Spector, T.D. (Timothy), Stancáková, A. (Alena), Stanton, A. (Alice), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swift, A.J. (Amy), Syvänen, A.C., Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K.V. (Kirill), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M.D. (Martin), Tremoli, E. (Elena), Uitterlinden, A.G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), Van Duijn, C.M. (Cornelia M.), Iperen, E.P.A. (Erik) van, Vasan, R.S. (Ramachandran S.), Verwoert, G.C. (Germaine), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B.F. (Benjamin), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L.V. (Louise V.), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weder, A.B. (Alan), Westra, H.J. (Harm-Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J.F. (James F.), Wong, T.Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jiefen), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R.S. (Richard S.), Mohlke, K.L. (Karen), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, L.M. (Lobke), Willer, C.J. (Cristen), Franke, L. (Lude), Hovingh, G.K. (Kees), Taylor, K.D. (Kent), Dedoussis, G.V. (George), Sever, P. (Peter), Wong, A. (Andrew), Kao, W.H.L. (Wen), Assimes, T.L. (Themistocles), Njølstad, I. (Inger), Schwarz, P.E.H. (Peter), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. (Mark), Melander, O. (Olle), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), März, W. (Winfried), Kumari, M. (Meena), Salomaa, V. (Veikko), Chen, Y.D. (Y.), Rotter, J.I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. (Edward), Kuulasmaa, K. (Kari), Franks, P.W. (Paul), Hamsten, A. (Anders), Wichmann, H.E. (Heinz Erich), Palmer, C.N.A. (Colin), Stefansson, K. (Kari), Ridker, P.M. (Paul), Loos, R.J.F. (Ruth), Chakravarti, A. (Aravinda), Deloukas, P. (Panagiotis), Morris, A.P. (Andrew), Newton-Cheh, C. (C.), and Munroe, P. (Patricia)
Abstract: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
Published: 2016
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18. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Ehret, G. B. (Georg B.), Ferreira, T. (Teresa), Chasman, D. I. (Daniel I.), Jackson, A. U. (Anne U.), Schmidt, E. M. (Ellen M.), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'an), Donnelly, L. A. (Louise A.), Kanoni, S. (Stavroula), Petersen, A. -. (Ann -Kristin), Pihurl, V. (Vasyl), Strawbridge, R. J. (Rona J.), Shungin, D. (Dmitry), Hughes, M. F. (Maria F.), Meirelles, O. (Osorio), Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M. E. (Marcus E.), Guo, X. (Xiuqing), Lyytikainen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Nidas), Nolte, I. M. (Ilja M.), Magnusson, P. K. (Patrik K.), Salfati, E. L. (Elias L.), Rallidis, L. S. (Loukianos S.), Theusch, E. (Elizabeth), Smith, A. J. (Andrew J. P.), Folkersen, L. (Lasse), Witkowska, K. (Kate), Pers, T. H. (Tune H.), Joehanes, R. (Roby), Kim, S. K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R. (Rick), Johnson, A. D. (Andrew D.), Warren, H. (Helen), Kim, Y. J. (Young Jin), Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. O. (Bamidele O.), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L. S. (Linda S.), Amin, N. (Najaf), Arkingl, D. E. (Dan E.), Axelsson, T. (Tomas), Baldassarre, D. (Damian), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M. R. (Michael R.), Barroso, I. (Ines), Bevan, S. (Stephen), Bis, J. C. (Joshua C.), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Boomsma, D. I. (Dorret I.), Bornstein, S. R. (Stefan R.), Brown, M. J. (Morris J.), Burnier, M. (Michel), Cabrera, C. P. (Claudia P.), Chambers, J. C. (John C.), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P. S. (Peter S.), Chung, R.-H. (Ren-Hua), Collins, F. S. (Francis S.), Connell, J. M. (John M.), Doring, A. (Angela), Dallongeville, J. (Jean), Danesh, J. (John), de Faire, U. (Ulf), Delgado, G. (Graciela), Dominiczak, A. F. (Anna F.), Doney, A. S. (Alex S. F.), Drenos, F. (Fotios), Edkins, S. (Sarah), Eicher, J. D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tonu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fai, T. (Tove), Farra, M. (Martin), Felixl, J. F. (Janine F.), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschinil, N. (Nora), Franco, O. H. (Oscar H.), Franco-Cereceda, A. (Anders), Fraser, R. M. (Ross M.), Ganesh, S. K. (Santhi K.), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goe, A. (Anuj), Goodall, A. H. (Alison H.), Goodarzi, M. (Mark), Gorski, M. (Mathias), Grassler, J. (Jurgen), Groves, C. J. (Christopher J.), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Goran), Hartikainen, A.-L. (Anna-Liisa), Hassinen, M. (Maija), Havulinna, A. S. (Aki S.), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.-H. (Karl-Heinz), Hicks, A. A. (Andrew A.), Hingorani, A. D. (Aroon D.), Hirschhorn, J. N. (Joel N.), Hofmanl, A. (Albert), Holmen, J. (Jostein), Holmen, O. L. (Oddgeir Lingaas), Hottenga, J.-J. (Jouke-Jan), Howard, P. (Phil), Hsiung, C. A. (Chao A.), Hunt, S. C. (Steven C.), Ikram, M. A. (M. Arfan), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R. A. (Richard A.), Kahonen, M. (Mika), Kang, H. M. (Hyun Min), Kathiresan, S. (Sekar), Keating, B. J. (Brendan J.), Khaw, K.-T. (Kay-Tee), Kim, Y. K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J. S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R. M. (Ronald M.), Kuh, D. (Diana), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Lee, N. R. (Nanette R.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindstrom, J. (Jaana), Lobbens, S. (Stephane), Mannisto, S. (Satu), Muller, G. (Gabriele), Muller-Nurasyid, M. (Martina), Mach, F. (Francois), Markus, H. S. (Hugh S.), Marouli, E. (Eirini), McCarthy, M. I. (Mark I.), McKenzie, C. A. (Colin A.), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M. E. (May E.), Morris, A. D. (Andrew D.), Morrison, A. C. (Alanna C.), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C. J. (Christopher J.), O'Reilly, P. F. (Paul F.), Ong, K. K. (Ken K.), Paccaud, F. (Fred), Palmer, C. D. (Cameron D.), Parsa, A. (Afshin), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W.), Perola, M. (Markus), Peters, A. (Annette), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Psaty, B. M. (Bruce M.), Quertermous, T. (Thomas), Rao, D. C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N. W. (N. William), Renstrom, F. (Frida), Rettig, R. (Rainer), Rice, K. M. (Kenneth M.), Roberts, R. (Robert), Rose, L. M. (Lynda M.), Rossouw, J. (Jacques), Samani, N. J. (Nilesh J.), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W. H. (Wayne H-H), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smit, J. H. (Johannes H.), Smith, A. V. (Albert V.), Sosa, M. X. (Maria X.), Spector, T. D. (Tim D.), Stancakova, A. (Alena), Stanton, A. V. (Alice V.), Stirrups, K. E. (Kathleen E.), Stringham, H. M. (Heather M.), Sundstrom, J. (Johan), Swift, A. J. (Amy J.), Syvanen, A.-C. (Ann-Christine), Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K. V. (Kirill V.), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M. D. (Martin D.), Tremoli, E. (Elena), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), van Duijn, C. M. (Cornelia M.), van Iperen, E. P. (Erik P. A.), Vasan, R. S. (Ramachandran S.), Verwoert, G. C. (Germaine C.), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B. F. (Benjamin F.), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L. V. (Louise V.), Wareham, N. J. (Nicholas J.), Watldns, H. (Hugh), Weder, A. B. (Alan B.), Westra, H. J. (Harm Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J. F. (James F.), Wong, T. Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jie), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R. S. (Richard S.), Mohlke, K. L. (Karen L.), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, H. J. (Hinco J.), Willer, C. J. (Cristen J.), Franke, L. (Lude), Hovingh, G. K. (G. Kees), Taylor, K. D. (Kent D.), Dedoussis, G. (George), Sever, P. (Peter), Wong, A. (Andrew), Lind, L. (Lars), Assimes, T. L. (Themistocles L.), Njolstad, I. (Inger), Schwarz, P. E. (Peter E. H.), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. J. (Mark J.), Melander, E. (E.), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimaki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), Marz, W. (Winfried), Kumar, M. (Meena), Salomaa, V. (Veikko), Chen, Y. I. (Yii-Der I.), Rotter, J. I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. G. (Edward G.), Kuulasmaa, K. (Kari), Franks, P. W. (Paul W.), Hamsten, A. (Anders), Wichmann, H.-E. (H-Erich), Palmer, C. N. (Colin N. A.), Stefansson, K. (Kari), Ridker, P. M. (Paul M.), Loos, R. J. (Ruth J. F.), Chalcravarti, A. (Aravinda), Deloukas, P. (Panos), Morris, A. P. (Andrew P.), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), Ehret, G. B. (Georg B.), Ferreira, T. (Teresa), Chasman, D. I. (Daniel I.), Jackson, A. U. (Anne U.), Schmidt, E. M. (Ellen M.), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'an), Donnelly, L. A. (Louise A.), Kanoni, S. (Stavroula), Petersen, A. -. (Ann -Kristin), Pihurl, V. (Vasyl), Strawbridge, R. J. (Rona J.), Shungin, D. (Dmitry), Hughes, M. F. (Maria F.), Meirelles, O. (Osorio), Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M. E. (Marcus E.), Guo, X. (Xiuqing), Lyytikainen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Nidas), Nolte, I. M. (Ilja M.), Magnusson, P. K. (Patrik K.), Salfati, E. L. (Elias L.), Rallidis, L. S. (Loukianos S.), Theusch, E. (Elizabeth), Smith, A. J. (Andrew J. P.), Folkersen, L. (Lasse), Witkowska, K. (Kate), Pers, T. H. (Tune H.), Joehanes, R. (Roby), Kim, S. K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R. (Rick), Johnson, A. D. (Andrew D.), Warren, H. (Helen), Kim, Y. J. (Young Jin), Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. O. (Bamidele O.), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L. S. (Linda S.), Amin, N. (Najaf), Arkingl, D. E. (Dan E.), Axelsson, T. (Tomas), Baldassarre, D. (Damian), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M. R. (Michael R.), Barroso, I. (Ines), Bevan, S. (Stephen), Bis, J. C. (Joshua C.), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Boomsma, D. I. (Dorret I.), Bornstein, S. R. (Stefan R.), Brown, M. J. (Morris J.), Burnier, M. (Michel), Cabrera, C. P. (Claudia P.), Chambers, J. C. (John C.), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P. S. (Peter S.), Chung, R.-H. (Ren-Hua), Collins, F. S. (Francis S.), Connell, J. M. (John M.), Doring, A. (Angela), Dallongeville, J. (Jean), Danesh, J. (John), de Faire, U. (Ulf), Delgado, G. (Graciela), Dominiczak, A. F. (Anna F.), Doney, A. S. (Alex S. F.), Drenos, F. (Fotios), Edkins, S. (Sarah), Eicher, J. D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tonu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fai, T. (Tove), Farra, M. (Martin), Felixl, J. F. (Janine F.), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschinil, N. (Nora), Franco, O. H. (Oscar H.), Franco-Cereceda, A. (Anders), Fraser, R. M. (Ross M.), Ganesh, S. K. (Santhi K.), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goe, A. (Anuj), Goodall, A. H. (Alison H.), Goodarzi, M. (Mark), Gorski, M. (Mathias), Grassler, J. (Jurgen), Groves, C. J. (Christopher J.), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Goran), Hartikainen, A.-L. (Anna-Liisa), Hassinen, M. (Maija), Havulinna, A. S. (Aki S.), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.-H. (Karl-Heinz), Hicks, A. A. (Andrew A.), Hingorani, A. D. (Aroon D.), Hirschhorn, J. N. (Joel N.), Hofmanl, A. (Albert), Holmen, J. (Jostein), Holmen, O. L. (Oddgeir Lingaas), Hottenga, J.-J. (Jouke-Jan), Howard, P. (Phil), Hsiung, C. A. (Chao A.), Hunt, S. C. (Steven C.), Ikram, M. A. (M. Arfan), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R. A. (Richard A.), Kahonen, M. (Mika), Kang, H. M. (Hyun Min), Kathiresan, S. (Sekar), Keating, B. J. (Brendan J.), Khaw, K.-T. (Kay-Tee), Kim, Y. K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J. S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R. M. (Ronald M.), Kuh, D. (Diana), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Lee, N. R. (Nanette R.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindstrom, J. (Jaana), Lobbens, S. (Stephane), Mannisto, S. (Satu), Muller, G. (Gabriele), Muller-Nurasyid, M. (Martina), Mach, F. (Francois), Markus, H. S. (Hugh S.), Marouli, E. (Eirini), McCarthy, M. I. (Mark I.), McKenzie, C. A. (Colin A.), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M. E. (May E.), Morris, A. D. (Andrew D.), Morrison, A. C. (Alanna C.), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C. J. (Christopher J.), O'Reilly, P. F. (Paul F.), Ong, K. K. (Ken K.), Paccaud, F. (Fred), Palmer, C. D. (Cameron D.), Parsa, A. (Afshin), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W.), Perola, M. (Markus), Peters, A. (Annette), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Psaty, B. M. (Bruce M.), Quertermous, T. (Thomas), Rao, D. C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N. W. (N. William), Renstrom, F. (Frida), Rettig, R. (Rainer), Rice, K. M. (Kenneth M.), Roberts, R. (Robert), Rose, L. M. (Lynda M.), Rossouw, J. (Jacques), Samani, N. J. (Nilesh J.), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W. H. (Wayne H-H), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smit, J. H. (Johannes H.), Smith, A. V. (Albert V.), Sosa, M. X. (Maria X.), Spector, T. D. (Tim D.), Stancakova, A. (Alena), Stanton, A. V. (Alice V.), Stirrups, K. E. (Kathleen E.), Stringham, H. M. (Heather M.), Sundstrom, J. (Johan), Swift, A. J. (Amy J.), Syvanen, A.-C. (Ann-Christine), Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K. V. (Kirill V.), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M. D. (Martin D.), Tremoli, E. (Elena), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), van Duijn, C. M. (Cornelia M.), van Iperen, E. P. (Erik P. A.), Vasan, R. S. (Ramachandran S.), Verwoert, G. C. (Germaine C.), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B. F. (Benjamin F.), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L. V. (Louise V.), Wareham, N. J. (Nicholas J.), Watldns, H. (Hugh), Weder, A. B. (Alan B.), Westra, H. J. (Harm Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J. F. (James F.), Wong, T. Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jie), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R. S. (Richard S.), Mohlke, K. L. (Karen L.), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, H. J. (Hinco J.), Willer, C. J. (Cristen J.), Franke, L. (Lude), Hovingh, G. K. (G. Kees), Taylor, K. D. (Kent D.), Dedoussis, G. (George), Sever, P. (Peter), Wong, A. (Andrew), Lind, L. (Lars), Assimes, T. L. (Themistocles L.), Njolstad, I. (Inger), Schwarz, P. E. (Peter E. H.), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. J. (Mark J.), Melander, E. (E.), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimaki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), Marz, W. (Winfried), Kumar, M. (Meena), Salomaa, V. (Veikko), Chen, Y. I. (Yii-Der I.), Rotter, J. I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. G. (Edward G.), Kuulasmaa, K. (Kari), Franks, P. W. (Paul W.), Hamsten, A. (Anders), Wichmann, H.-E. (H-Erich), Palmer, C. N. (Colin N. A.), Stefansson, K. (Kari), Ridker, P. M. (Paul M.), Loos, R. J. (Ruth J. F.), Chalcravarti, A. (Aravinda), Deloukas, P. (Panos), Morris, A. P. (Andrew P.), Newton-Cheh, C. (Christopher), and Munroe, P. B. (Patricia B.)
Abstract: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure–associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure–related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
Published: 2016

19. Correction: The influence of age and sex on genetic associations with adult body size and shape : a large-scale genome-wide interaction study.

Author: Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der Most, P.J., Völker, U., Vohl, M.C., Vonk, J.M., Waldenberger, M., Walker, R.W., Wennauer, R., Widén, E., Willemsen, G., Wilsgaard, T., Wright, A.F., Zillikens, M.C., van Dijk, S.C., van Schoor, N.M., Asselbergs, F.W., de Bakker, P.I., Beckmann, J.S., Beilby, J., Bennett, D.A., Bergman, R.N., Bergmann, S., Böger, C.A., Boehm, B.O., Boerwinkle, E., Boomsma, D.I., Bornstein, S.R., Bottinger, E.P., Bouchard, C., Chambers, J.C., Chanock, S.J., Chasman, D.I., Cucca, F., Cusi, D., Dedoussis, G., Erdmann, J., Eriksson, J.G., Evans, D.A., de Faire, U., Farrall, M., Ferrucci, L., Ford, I., Franke, L., Franks, P.W., Froguel, P., Gansevoort, R.T., Gieger, C., Grönberg, H., Gudnason, V., Gyllensten, U., Hall, P., Hamsten, A., van der Harst, P., Hayward, C., Heliövaara, M., Hengstenberg, C., Hicks, A.A., Hingorani, A., Hofman, A., Hu, F., Huikuri, H.V., Hveem, K., James, A.L., Jordan, J.M., Jula, A., Kähönen, M., Kajantie, E., Kathiresan, S., Kiemeney, L.A., Kivimaki, M., Knekt, P.B., Koistinen, H.A., Kooner, J.S., Koskinen, S., Kuusisto, J., Maerz, W., Martin, N.G., Laakso, M., Lakka, T.A., Lehtimäki, T., Lettre, G., Levinson, D.F., Lind, L., Lokki, M.L., Mäntyselkä, P., Melbye, M., Metspalu, A., Mitchell, B.D., Moll, F.L., Murray, J.C., Musk, A.W., Nieminen, M.S., Njølstad, I., Ohlsson, C., Oldehinkel, A.J., Oostra, B.A., Palmer, L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., Loos, R.J., Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der 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Koistinen, H.A., Kooner, J.S., Koskinen, S., Kuusisto, J., Maerz, W., Martin, N.G., Laakso, M., Lakka, T.A., Lehtimäki, T., Lettre, G., Levinson, D.F., Lind, L., Lokki, M.L., Mäntyselkä, P., Melbye, M., Metspalu, A., Mitchell, B.D., Moll, F.L., Murray, J.C., Musk, A.W., Nieminen, M.S., Njølstad, I., Ohlsson, C., Oldehinkel, A.J., Oostra, B.A., Palmer, L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., and Loos, R.J.
Abstract: This corrects the article DOI: 10.1371/journal.pgen.1005378.
Published: 2016

20. Determination of a Normal value for HOMA-IR and cut-off Value for Non-Alcoholic Fatty Liver Disease

Author: Petäjä, E.M., primary, Zhou, Y., additional, Peltonen, M., additional, Jouslahti, P., additional, Männistö, S., additional, Keinänen-Kiukaanniemi, S., additional, Saltevo, J., additional, and Yki-Järvinen, H., additional
Published: 2016
Full Text: View/download PDF

21. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author: Winkler, T.W. (Thomas W.), Justice, A.E. (Anne), Graff, M.J. (Maud J.L.), Barata, L. (Llilda), Feitosa, M.F. (Mary Furlan), Chu, S. (Su), Czajkowski, J. (Jacek), Esko, T. (Tõnu), Fall, M. (Magnus), Kilpeläinen, T.O. (Tuomas), Lu, Y. (Yingchang), Mägi, R. (Reedik), Mihailov, E. (Evelin), Pers, T.H. (Tune), Rüeger, S. (Sina), Teumer, A. (Alexander), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Heard-Costa, N.L. (Nancy), Karjalainen, J. (Juha), Lagou, V. (Vasiliki), Mahajan, A. (Anubha), Neinast, M.D. (Michael D.), Prokopenko, I. (Inga), Simino, J. (Jeannette), Teslovich, T.M. (Tanya M.), Jansen, R., Westra, H.J. (Harm-Jan), White, C.C. (Charles), Absher, D. (Devin), Ahluwalia, T.S. (Tarunveer Singh), Ahmad, S. (Shafqat), Albrecht, E. (Eva), Alves, A.C. (Alexessander Couto), Bragg-Gresham, J.L. (Jennifer L.), Craen, A.J. (Anton) de, Bis, J.C. (Joshua), Bonnefond, A. (Amélie), Boucher, G. (Gabrielle), Cadby, G. (Gemma), Cheng, Y.-C. (Yu-Ching), Chiang, C.W. (Charleston W K), Delgado, G., Demirkan, A. (Ayşe), Dueker, N. (Nicole), Eklund, N. (Niina), Eiriksdottir, G. (Gudny), Eriksson, J. (Joel), Feenstra, B. (Bjarke), Fischer, K. (Krista), Frau, F. (Francesca), Galesloot, T.E. (Tessel), Geller, F. (Frank), Goel, A. (Anuj), Gorski, M. (Mathias), Grammer, T.B. (Tanja), Gustafsson, S. (Stefan), Haitjema, S. (Saskia), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Jacobs, K.B. (Kevin), Johansson, A. (Åsa), Kaakinen, M. (Marika), Kleber, M.E. (Marcus), Lahti, J. (Jari), Leach, I.M. (Irene Mateo), Lehne, B. (Benjamin), Liu, Y. (Youfang), Lo, K.S., Lorentzon, M. (Mattias), Luan, J. (Jian'An), Madden, P.A. (Pamela), Mangino, M. (Massimo), McKnight, B. (Barbara), Medina-Gomez, C. (Carolina), Monda, K.L. (Keri), Montasser, M.E. (May E.), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Panoutsopoulou, K. (Kalliope), Pascoe, L. (Laura), Paternoster, L. (Lavinia), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rizzi, F. (Federica), Rose, L.M. (Lynda), Ryan, K.A. (Kathy A.), Salo, P. (Perttu), Sanna, S. (Serena), Scharnagl, H. (Hubert), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Southam, L. (Lorraine), Stancáková, A. (Alena), Steinthorsdottir, V. (Valgerdur), Strawbridge, R.J. (Rona), Sung, Y.J. (Yun Ju), Tachmazidou, I. (Ioanna), Tanaka, T. (Toshiko), Thorleifsson, G. (Gudmar), Trompet, S. (Stella), Pervjakova, N. (Natalia), Tyrer, J.P. (Jonathan), Vandenput, L. (Liesbeth), Van Der Laan, S.W. (Sander W.), Velde, N. (Nathalie) van der, Setten, J. (Jessica) van, Vliet-Ostaptchouk, J.V. (Jana) van, Verweij, N. (Niek), Vlachopoulou, E. (Efthymia), Waite, L. (Lindsay), Wang, S.R. (Sophie), Wang, Z. (Zhaoming), Wild, S.H. (Sarah), Willenborg, C. (Christina), Wilson, J.F. (James), Wong, A. (Andrew), Yang, J. (Jian), Yengo, L. (Loic), Yerges-Armstrong, L.M. (Laura), Yu, L. (Lei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Andersson, E.A. (Ehm Astrid), Bakker, S.J.L. (Stephan), Baldassarre, D. (Damiano), Banasik, K. (Karina), Barcella, M. (Matteo), Barlassina, C. (Cristina), Bellis, C. (Claire), Benaglio, P. (Paola), Blangero, J. (John), Blüher, M. (Matthias), Bonnet, F. (Fabrice), Bonnycastle, L.L. (Lori), Boyd, H.A. (Heather), Bruinenberg, M. (M.), Buchman, A.S. (Aron S.), Campbell, H. (Harry), Chen, Y.D. (Y.), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Cole, J.W. (John W.), Collins, F.S. (Francis), Geus, E.J.C. (Eco) de, Groot, L.C.P.G.M. (Lisette) de, Dimitriou, M. (Maria), Duan, J. (Jubao), Enroth, S. (Stefan), Eury, E. (Elodie), Farmaki, A.-E. (Aliki-Eleni), Forouhi, N.G. (Nita), Friedrich, N. (Nele), Gejman, P.V. (Pablo), Gigante, B. (Bruna), Glorioso, N. (Nicola), Go, A.T.J.I. (Attie), Gottesman, R.F. (Rebecca), Gräßler, J. (Jürgen), Grallert, H. (Harald), Grarup, N. (Niels), Gu, Y.-M. (Yu-Mei), Broer, L. (Linda), Ham, A.C. (Annelies), Hansen, T. (T.), Harris, T.B. (Tamara), Hartman, C.A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nick), Hattersley, A.T. (Andrew), Heath, A.C. (Andrew), Henders, A.K. (Anjali), Hernandez, D.G. (Dena), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Hui, J. (Jennie), Husemoen, L.L. (Lise L.), Hutri-Kähönen, N. (Nina), Hysi, P.G. (Pirro), Illig, T. (Thomas), Jager, P.L. (Philip) de, Jalilzadeh, S. (Shapour), Jorgensen, T. (Torben), Jukema, J.W. (Jan Wouter), Juonala, M. (Markus), Kanoni, S. (Stavroula), Karaleftheri, M. (Maria), Khaw, K.T., Kinnunen, L. (Leena), Kittner, T. (Thomas), Koenig, W. (Wolfgang), Kolcic, I. (Ivana), Kovacs, P. (Peter), Krarup, N.T. (Nikolaj T.), Kratzer, W. (Wolfgang), Krüger, J. (Janine), Kuh, D. (Diana), Kumari, M. (Meena), Kyriakou, T. (Theodosios), Langenberg, C. (Claudia), Lannfelt, L. (Lars), Lanzani, C. (Chiara), Lotay, V. (Vaneet), Launer, L.J. (Lenore), Leander, K. (Karin), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y.-P. (Yan-Ping), Lobbens, S. (Stéphane), Luben, R.N. (Robert), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Magnusson, P.K. (Patrik), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Milani, L. (Lili), Montgomery, G.W. (Grant W.), Morris, A.P. (Andrew), Narisu, N. (Narisu), Nelis, M. (Mari), Ong, K.K. (Ken), Palotie, A. (Aarno), Perusse, L. (Louis), Pichler, I. (Irene), Pilia, M.G. (Maria Grazia), Pouta, A. (Anneli), Rheinberger, M. (Myriam), Ribel-Madsen, R. (Rasmus), Richards, M. (Marcus), Rice, K.M. (Kenneth), Rice, T.K. (Treva K.), Rivolta, C. (Carlo), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sarzynski, M.A. (Mark A.), Scholtens, S. (Salome), Scott, R.A. (Robert), Scott, W.R. (William R.), Sebert, S. (Sylvain), Sengupta, S. (Sebanti), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Silveira, A. (Angela), Slagboom, P.E. (Eline), Smit, J.H. (Jan), Sparsø, T. (Thomas), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Stringham, H.M. (Heather), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Syvänen, A.C., Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tsafantakis, E. (Emmanouil), Most, P.J. (Peter) van der, Völker, U. (Uwe), Vohl, M.-C. (Marie-Claude), Vonk, J.M. (Judith), Waldenberger, M. (Melanie), Walker, R.W. (Ryan W.), Wennauer, R. (Roman), Widen, E., Willemsen, G.A.H.M. (Gonneke), Wilsgaard, T. (Tom), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Van Dijk, S. (Suzanne), Schoor, N.M. (Natasja) van, Asselbergs, F.W. (Folkert), Bakker, P.I.W. (Paul) de, Beckmann, J.S. (Jacques), Beilby, J.P. (John), Bennett, D.A. (David A.), Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Böger, C.A. (Carsten), Boehm, B.O. (Bernhard), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Bottinger, E.P. (Erwin), Bouchard, C. (Claude), Chambers, J.C. (John), Chanock, S.J. (Stephen), Chasman, D.I. (Daniel), Cucca, F. (Francesco), Cusi, D. (Daniele), Dedoussis, G.V. (George), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evans, D., Faire, U. (Ulf) de, Farrall, M. (Martin), Ferrucci, L. (Luigi), Ford, I. (Ian), Franke, L. (Lude), Franks, P.W. (Paul), Froguel, P. (Philippe), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Grönberg, H. (Henrik), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hall, P. (Per), Hamsten, A. (Anders), Harst, P. (Pim) van der, Hayward, C. (Caroline), Heliovaara, M. (Markku), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hofman, A. (Albert), Hu, F. (Frank), Huikuri, H.V. (Heikki), Hveem, K. (Kristian), James, A. (Alan), Jordan, J.M. (Joanne M.), Jula, A. (Antti), Kähönen, M. (Mika), Kajantie, E. (Eero), Kathiresan, S. (Sekar), Kiemeney, L.A.L.M. (Bart), Kivimaki, M. (Mika), Knekt, P., Koistinen, H. (Heikki), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kuusisto, J. (Johanna), Maerz, W. (Winfried), Martin, N.G. (Nicholas), Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Levinson, D.F. (Douglas), Kao, W.H.L. (Wen), Lokki, M.L., Mäntyselkä, P. (Pekka), Melbye, M. (Mads), Metspalu, A. (Andres), Mitchell, B.D. (Braxton), Moll, F.L. (Frans), Murray, J.C. (Jeffrey), Musk, A.W. (Arthur), Nieminen, M.S. (Markku), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palmer, C. (Cameron), Pankow, J.S. (James), Pasterkamp, G. (Gerard), Pedersen, N.L. (Nancy), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Quertermous, T. (Thomas), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rauramaa, R. (Rainer), Ridker, P.M. (Paul), Rioux, J.D. (John), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Saltevo, J. (Juha), Sattar, N. (Naveed), Schunkert, H. (Heribert), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Sinisalo, J. (Juha), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Staessen, J.A. (Jan A.), Stefania, B. (Bandinelli), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tardif, J.-C. (Jean-Claude), Tremoli, E. (Elena), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Verbeek, A.L.M., Vermeulen, S.H.H.M. (Sita), Viikari, J. (Jorma), Vitart, V. (Veronique), Völzke, H. (Henry), Vollenweider, P. (Peter), Waeber, G. (Gérard), Walker, M. (Mark), Wallaschofski, H. (Henri), Wareham, N.J. (Nick), Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Chakravarti, A. (Aravinda), Clegg, D.J. (Deborah J.), Cupples, L.A. (Adrienne), Gordon-Larsen, P. (Penny), Jaquish, C.E. (Cashell), Rao, D.C. (Dabeeru C.), Abecasis, G.R. (Goncalo R.), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Hunter, D. (David), Ingelsson, E. (Erik), Kaplan, R.C. (Robert), McCarthy, M.I. (Mark I.), Mohlke, K.L. (Karen), O´Connell, J.R., Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Hirschhorn, J.N. (Joel), Lindgren, C.M. (Cecilia M.), Heid, I.M. (Iris), North, K.E. (Kari), Borecki, I.B. (Ingrid), Kutalik, Z. (Zoltán), Loos, R.J.F. (Ruth), Winkler, T.W. (Thomas W.), Justice, A.E. (Anne), Graff, M.J. (Maud J.L.), Barata, L. (Llilda), Feitosa, M.F. (Mary Furlan), Chu, S. (Su), Czajkowski, J. (Jacek), Esko, T. (Tõnu), Fall, M. (Magnus), Kilpeläinen, T.O. (Tuomas), Lu, Y. (Yingchang), Mägi, R. (Reedik), Mihailov, E. (Evelin), Pers, T.H. (Tune), Rüeger, S. (Sina), Teumer, A. (Alexander), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Heard-Costa, N.L. (Nancy), Karjalainen, J. (Juha), Lagou, V. (Vasiliki), Mahajan, A. (Anubha), Neinast, M.D. (Michael D.), Prokopenko, I. (Inga), Simino, J. (Jeannette), Teslovich, T.M. (Tanya M.), Jansen, R., Westra, H.J. (Harm-Jan), White, C.C. (Charles), Absher, D. (Devin), Ahluwalia, T.S. (Tarunveer Singh), Ahmad, S. (Shafqat), Albrecht, E. (Eva), Alves, A.C. (Alexessander Couto), Bragg-Gresham, J.L. (Jennifer L.), Craen, A.J. (Anton) de, Bis, J.C. (Joshua), Bonnefond, A. (Amélie), Boucher, G. (Gabrielle), Cadby, G. (Gemma), Cheng, Y.-C. (Yu-Ching), Chiang, C.W. (Charleston W K), Delgado, G., Demirkan, A. (Ayşe), Dueker, N. (Nicole), Eklund, N. (Niina), Eiriksdottir, G. (Gudny), Eriksson, J. (Joel), Feenstra, B. (Bjarke), Fischer, K. (Krista), Frau, F. (Francesca), Galesloot, T.E. (Tessel), Geller, F. (Frank), Goel, A. (Anuj), Gorski, M. (Mathias), Grammer, T.B. (Tanja), Gustafsson, S. (Stefan), Haitjema, S. (Saskia), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Jacobs, K.B. (Kevin), Johansson, A. (Åsa), Kaakinen, M. (Marika), Kleber, M.E. (Marcus), Lahti, J. (Jari), Leach, I.M. (Irene Mateo), Lehne, B. (Benjamin), Liu, Y. (Youfang), Lo, K.S., Lorentzon, M. (Mattias), Luan, J. (Jian'An), Madden, P.A. (Pamela), Mangino, M. (Massimo), McKnight, B. (Barbara), Medina-Gomez, C. (Carolina), Monda, K.L. (Keri), Montasser, M.E. (May E.), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Panoutsopoulou, K. (Kalliope), Pascoe, L. (Laura), Paternoster, L. (Lavinia), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rizzi, F. (Federica), Rose, L.M. (Lynda), Ryan, K.A. (Kathy A.), Salo, P. (Perttu), Sanna, S. (Serena), Scharnagl, H. (Hubert), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Southam, L. (Lorraine), Stancáková, A. (Alena), Steinthorsdottir, V. (Valgerdur), Strawbridge, R.J. (Rona), Sung, Y.J. (Yun Ju), Tachmazidou, I. (Ioanna), Tanaka, T. (Toshiko), Thorleifsson, G. (Gudmar), Trompet, S. (Stella), Pervjakova, N. (Natalia), Tyrer, J.P. (Jonathan), Vandenput, L. (Liesbeth), Van Der Laan, S.W. (Sander W.), Velde, N. (Nathalie) van der, Setten, J. (Jessica) van, Vliet-Ostaptchouk, J.V. (Jana) van, Verweij, N. (Niek), Vlachopoulou, E. (Efthymia), Waite, L. (Lindsay), Wang, S.R. (Sophie), Wang, Z. (Zhaoming), Wild, S.H. (Sarah), Willenborg, C. (Christina), Wilson, J.F. (James), Wong, A. (Andrew), Yang, J. (Jian), Yengo, L. (Loic), Yerges-Armstrong, L.M. (Laura), Yu, L. (Lei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Andersson, E.A. (Ehm Astrid), Bakker, S.J.L. (Stephan), Baldassarre, D. (Damiano), Banasik, K. (Karina), Barcella, M. (Matteo), Barlassina, C. (Cristina), Bellis, C. (Claire), Benaglio, P. (Paola), Blangero, J. (John), Blüher, M. (Matthias), Bonnet, F. (Fabrice), Bonnycastle, L.L. (Lori), Boyd, H.A. (Heather), Bruinenberg, M. (M.), Buchman, A.S. (Aron S.), Campbell, H. (Harry), Chen, Y.D. (Y.), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Cole, J.W. (John W.), Collins, F.S. (Francis), Geus, E.J.C. (Eco) de, Groot, L.C.P.G.M. (Lisette) de, Dimitriou, M. (Maria), Duan, J. (Jubao), Enroth, S. (Stefan), Eury, E. (Elodie), Farmaki, A.-E. (Aliki-Eleni), Forouhi, N.G. (Nita), Friedrich, N. (Nele), Gejman, P.V. (Pablo), Gigante, B. (Bruna), Glorioso, N. (Nicola), Go, A.T.J.I. (Attie), Gottesman, R.F. (Rebecca), Gräßler, J. (Jürgen), Grallert, H. (Harald), Grarup, N. (Niels), Gu, Y.-M. (Yu-Mei), Broer, L. (Linda), Ham, A.C. (Annelies), Hansen, T. (T.), Harris, T.B. (Tamara), Hartman, C.A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nick), Hattersley, A.T. (Andrew), Heath, A.C. (Andrew), Henders, A.K. (Anjali), Hernandez, D.G. (Dena), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Hui, J. (Jennie), Husemoen, L.L. (Lise L.), Hutri-Kähönen, N. (Nina), Hysi, P.G. (Pirro), Illig, T. (Thomas), Jager, P.L. (Philip) de, Jalilzadeh, S. (Shapour), Jorgensen, T. (Torben), Jukema, J.W. (Jan Wouter), Juonala, M. (Markus), Kanoni, S. (Stavroula), Karaleftheri, M. (Maria), Khaw, K.T., Kinnunen, L. (Leena), Kittner, T. (Thomas), Koenig, W. (Wolfgang), Kolcic, I. (Ivana), Kovacs, P. (Peter), Krarup, N.T. (Nikolaj T.), Kratzer, W. (Wolfgang), Krüger, J. (Janine), Kuh, D. (Diana), Kumari, M. (Meena), Kyriakou, T. (Theodosios), Langenberg, C. (Claudia), Lannfelt, L. (Lars), Lanzani, C. (Chiara), Lotay, V. (Vaneet), Launer, L.J. (Lenore), Leander, K. (Karin), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y.-P. (Yan-Ping), Lobbens, S. (Stéphane), Luben, R.N. (Robert), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Magnusson, P.K. (Patrik), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Milani, L. (Lili), Montgomery, G.W. (Grant W.), Morris, A.P. (Andrew), Narisu, N. (Narisu), Nelis, M. (Mari), Ong, K.K. (Ken), Palotie, A. (Aarno), Perusse, L. (Louis), Pichler, I. (Irene), Pilia, M.G. (Maria Grazia), Pouta, A. (Anneli), Rheinberger, M. (Myriam), Ribel-Madsen, R. (Rasmus), Richards, M. (Marcus), Rice, K.M. (Kenneth), Rice, T.K. (Treva K.), Rivolta, C. (Carlo), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sarzynski, M.A. (Mark A.), Scholtens, S. (Salome), Scott, R.A. (Robert), Scott, W.R. (William R.), Sebert, S. (Sylvain), Sengupta, S. (Sebanti), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Silveira, A. (Angela), Slagboom, P.E. (Eline), Smit, J.H. (Jan), Sparsø, T. (Thomas), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Stringham, H.M. (Heather), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Syvänen, A.C., Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tsafantakis, E. (Emmanouil), Most, P.J. (Peter) van der, Völker, U. (Uwe), Vohl, M.-C. (Marie-Claude), Vonk, J.M. (Judith), Waldenberger, M. (Melanie), Walker, R.W. (Ryan W.), Wennauer, R. (Roman), Widen, E., Willemsen, G.A.H.M. (Gonneke), Wilsgaard, T. (Tom), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Van Dijk, S. (Suzanne), Schoor, N.M. (Natasja) van, Asselbergs, F.W. (Folkert), Bakker, P.I.W. (Paul) de, Beckmann, J.S. (Jacques), Beilby, J.P. (John), Bennett, D.A. (David A.), Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Böger, C.A. (Carsten), Boehm, B.O. (Bernhard), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Bottinger, E.P. (Erwin), Bouchard, C. (Claude), Chambers, J.C. (John), Chanock, S.J. (Stephen), Chasman, D.I. (Daniel), Cucca, F. (Francesco), Cusi, D. (Daniele), Dedoussis, G.V. (George), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evans, D., Faire, U. (Ulf) de, Farrall, M. (Martin), Ferrucci, L. (Luigi), Ford, I. (Ian), Franke, L. (Lude), Franks, P.W. (Paul), Froguel, P. (Philippe), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Grönberg, H. (Henrik), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hall, P. (Per), Hamsten, A. (Anders), Harst, P. (Pim) van der, Hayward, C. (Caroline), Heliovaara, M. (Markku), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hofman, A. (Albert), Hu, F. (Frank), Huikuri, H.V. (Heikki), Hveem, K. (Kristian), James, A. (Alan), Jordan, J.M. (Joanne M.), Jula, A. (Antti), Kähönen, M. (Mika), Kajantie, E. (Eero), Kathiresan, S. (Sekar), Kiemeney, L.A.L.M. (Bart), Kivimaki, M. (Mika), Knekt, P., Koistinen, H. (Heikki), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kuusisto, J. (Johanna), Maerz, W. (Winfried), Martin, N.G. (Nicholas), Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Levinson, D.F. (Douglas), Kao, W.H.L. (Wen), Lokki, M.L., Mäntyselkä, P. (Pekka), Melbye, M. (Mads), Metspalu, A. (Andres), Mitchell, B.D. (Braxton), Moll, F.L. (Frans), Murray, J.C. (Jeffrey), Musk, A.W. (Arthur), Nieminen, M.S. (Markku), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palmer, C. (Cameron), Pankow, J.S. (James), Pasterkamp, G. (Gerard), Pedersen, N.L. (Nancy), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Quertermous, T. (Thomas), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rauramaa, R. (Rainer), Ridker, P.M. (Paul), Rioux, J.D. (John), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Saltevo, J. (Juha), Sattar, N. (Naveed), Schunkert, H. (Heribert), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Sinisalo, J. (Juha), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Staessen, J.A. (Jan A.), Stefania, B. (Bandinelli), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tardif, J.-C. (Jean-Claude), Tremoli, E. (Elena), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Verbeek, A.L.M., Vermeulen, S.H.H.M. (Sita), Viikari, J. (Jorma), Vitart, V. (Veronique), Völzke, H. (Henry), Vollenweider, P. (Peter), Waeber, G. (Gérard), Walker, M. (Mark), Wallaschofski, H. (Henri), Wareham, N.J. (Nick), Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Chakravarti, A. (Aravinda), Clegg, D.J. (Deborah J.), Cupples, L.A. (Adrienne), Gordon-Larsen, P. (Penny), Jaquish, C.E. (Cashell), Rao, D.C. (Dabeeru C.), Abecasis, G.R. (Goncalo R.), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Hunter, D. (David), Ingelsson, E. (Erik), Kaplan, R.C. (Robert), McCarthy, M.I. (Mark I.), Mohlke, K.L. (Karen), O´Connell, J.R., Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Hirschhorn, J.N. (Joel), Lindgren, C.M. (Cecilia M.), Heid, I.M. (Iris), North, K.E. (Kari), Borecki, I.B. (Ingrid), Kutalik, Z. (Zoltán), and Loos, R.J.F. (Ruth)
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for B
Published: 2015
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22. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci

Author: Gaulton, K. (Kyle), Ferreira, T. (Teresa), Lee, Y. (Yeji), Raimondo, A. (Anne), Mägi, R. (Reedik), Reschen, M.E. (Michael E.), Mahajan, A. (Anubha), Locke, A. (Adam), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Scott, R.A. (Robert), Prokopenko, I. (Inga), Scott, L.J. (Laura), Green, T. (Todd), Sparsø, T. (Thomas), Thuillier, D. (Dorothee), Yengo, L. (Loic), Grallert, H. (Harald), Wahl, S. (Simone), Frånberg, M. (Mattias), Strawbridge, R.J. (Rona), Kestler, H. (Hans), Chheda, H. (Himanshu), Eisele, L. (Lewin), Gustafsson, S. (Stefan), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Qi, L. (Lu), Karssen, L.C. (Lennart), Leeuwen, E.M. (Elisa) van, Willems, S.M. (Sara), Li, M. (Man), Chen, H. (Han), Fuchsberger, C. (Christian), Kwan, P. (Phoenix), Ma, C. (Clement), Linderman, M. (Michael), Lu, Y. (Yingchang), Thomsen, S.K. (Soren K.), Rundle, J.K. (Jana K.), Beer, N.L. (Nicola L.), Bunt, M. (Martijn) van de, Chalisey, A. (Anil), Kang, H.M. (Hyun Min), Voight, B.F. (Benjamin), Abecasis, G.R. (Gonçalo), Almgren, P. (Peter), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Blüher, M. (Matthias), Boeing, H. (Heiner), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin P.), Burtt, N.P. (Noël), Carey, J. (Jason), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David J.), Crenshaw, A. (Andrew), Dam, R.M. (Rob) van, Doney, A.S.F. (Alex), Dorkhan, M. (Mozhgan), Edkins, T. (Ted), Eriksson, J.G. (Johan G.), Esko, T. (Tõnu), Eury, E. (Elodie), Fadista, J. (João), Flannick, J. (Jason), Fontanillas, P. (Pierre), Fox, C.S. (Caroline), Franks, P.W. (Paul W.), Gertow, K. (Karl), Gieger, C. (Christian), Gigante, B. (Bruna), Gottesman, R.F. (Rebecca), Grant, G.B. (George), Grarup, N. (Niels), Groves, C.J. (Christopher J.), Hassinen, M. (Maija), Have, C.T. (Christian T.), Herder, C. (Christian), Holmen, O.L. (Oddgeir), Hreidarsson, A.B. (Astradur), Humphries, S.E. (Steve E.), Hunter, D.J. (David J.), Jackson, A.U. (Anne), Jonsson, A. (Anna), Jørgensen, M.E. (Marit E.), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Kerrison, N.D. (Nicola D.), Kinnunen, L. (Leena), Klopp, N. (Norman), Kong, A. (Augustine), Kovacs, P. (Peter), Kraft, P. (Peter), Kravic, J. (Jasmina), Langford, C. (Cordelia), Leander, K. (Karin), Liang, L. (Liming), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia M.), Lindholm, B. (Bengt), Linneberg, A. (Allan), Liu, C.-T. (Ching-Ti), Lobbens, S. (Stéphane), Luan, J. (Jian'fan), Lyssenko, V. (Valeriya), Männistö, S. (Satu), McLeod, O. (Olga), Meyer, J. (Jobst), Mihailov, E. (Evelin), Mirza, G. (Ghazala), Mühleisen, T.W. (Thomas), Müller-Nurasyid, M. (Martina), Navarro, C. (Carmen), Nöthen, M.M. (Markus), Oskolkov, N.N. (Nikolay N.), Owen, K.R. (Katharine), Palli, D. (Domenico), Pechlivanis, S. (Sonali), Peltonen, L. (Leena Johanna), Perry, J.R.B. (John), Platou, C.P. (Carl), Roden, M. (Michael), Ruderfer, D. (Douglas), Rybin, D. (Denis), Van Der Schouw, Y.T. (Yvonne T.), Sennblad, B. (Bengt), Sigurosson, G. (Gunnar), Stancáková, A. (Alena), Steinbach, D., Storm, P. (Petter), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Sun, Q., Thorand, B. (Barbara), Tikkanen, E. (Emmi), Tönjes, A. (Anke), Trakalo, J. (Joseph), Tremoli, E. (Elena), Tuomi, T. (Tiinamaija), Wennauer, R. (Roman), Wiltshire, S. (Steven), Wood, A.R. (Andrew), Zeggini, E. (Eleftheria), Dunham, I. (Ian), Birney, E. (Ewan), Pasquali, L. (Lorenzo), Ferrer, J. (Jorge), Loos, R.J.F. (Ruth), Dupuis, J. (Josée), Florez, J.C. (Jose), Boerwinkle, E.A. (Eric), Pankow, J.S. (James), Duijn, C.M. (Cornelia) van, Sijbrands, E.J.G. (Eric), Meigs, J.B. (James B.), Hu, F.B. (Frank), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Stumvoll, M. (Michael), Pedersen, N.L. (Nancy L.), Lind, L. (Lars), Keinanen-Kiukaanniemi, S. (Sirkka), Korpi-Hyövälti, E. (Eeva), Saaristo, T. (Timo), Saltevo, J. (Juha), Kuusisto, J. (Johanna), Laakso, M. (Markku), Metspalu, A. (Andres), Erbel, R. (Raimund), Jöckel, K.-H. (Karl-Heinz), Moebus, S. (Susanne), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Ingelsson, E. (Erik), Boehm, B.O. (Bernhard), Bergman, R.N. (Richard N.), Collins, F.S. (Francis S.), Mohlke, K.L. (Karen L.), Koistinen, H. (Heikki), Tuomilehto, J. (Jaakko), Hveem, K. (Kristian), Njølstad, I. (Inger), Deloukas, P. (Panagiotis), Donnelly, P.J. (Peter J.), Frayling, T.M. (Timothy), Hattersley, A.T. (Andrew), Faire, U. (Ulf) de, Hamsten, A. (Anders), Illig, T. (Thomas), Peters, A. (Annette), Cauchi, S. (Stephane), Sladek, R. (Rob), Froguel, P. (Philippe), Hansen, T. (Torben), Pedersen, O. (Oluf), Morris, A.D. (Andrew), Palmer, C.N.A. (Collin N. A.), Kathiresan, S. (Sekar), Melander, O. (Olle), Nilsson, P.M. (Peter M.), Groop, L. (Leif), Barroso, I.E. (Inês), Langenberg, C. (Claudia), Wareham, N.J. (Nicholas J.), O'Callaghan, C.A. (Christopher A.), Gloyn, A.L. (Anna), Altshuler, D. (David), Boehnke, M. (Michael), Teslovich, T.M. (Tanya M.), McCarthy, M.I. (Mark), Morris, A.P. (Andrew), Gaulton, K. (Kyle), Ferreira, T. (Teresa), Lee, Y. (Yeji), Raimondo, A. (Anne), Mägi, R. (Reedik), Reschen, M.E. (Michael E.), Mahajan, A. (Anubha), Locke, A. (Adam), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Scott, R.A. (Robert), Prokopenko, I. (Inga), Scott, L.J. (Laura), Green, T. (Todd), Sparsø, T. (Thomas), Thuillier, D. (Dorothee), Yengo, L. (Loic), Grallert, H. (Harald), Wahl, S. (Simone), Frånberg, M. (Mattias), Strawbridge, R.J. (Rona), Kestler, H. (Hans), Chheda, H. (Himanshu), Eisele, L. (Lewin), Gustafsson, S. (Stefan), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Qi, L. (Lu), Karssen, L.C. (Lennart), Leeuwen, E.M. (Elisa) van, Willems, S.M. (Sara), Li, M. (Man), Chen, H. (Han), Fuchsberger, C. (Christian), Kwan, P. (Phoenix), Ma, C. (Clement), Linderman, M. (Michael), Lu, Y. (Yingchang), Thomsen, S.K. (Soren K.), Rundle, J.K. (Jana K.), Beer, N.L. (Nicola L.), Bunt, M. (Martijn) van de, Chalisey, A. (Anil), Kang, H.M. (Hyun Min), Voight, B.F. (Benjamin), Abecasis, G.R. (Gonçalo), Almgren, P. (Peter), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Blüher, M. (Matthias), Boeing, H. (Heiner), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin P.), Burtt, N.P. (Noël), Carey, J. (Jason), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David J.), Crenshaw, A. (Andrew), Dam, R.M. (Rob) van, Doney, A.S.F. (Alex), Dorkhan, M. (Mozhgan), Edkins, T. (Ted), Eriksson, J.G. (Johan G.), Esko, T. (Tõnu), Eury, E. (Elodie), Fadista, J. (João), Flannick, J. (Jason), Fontanillas, P. (Pierre), Fox, C.S. (Caroline), Franks, P.W. (Paul W.), Gertow, K. (Karl), Gieger, C. (Christian), Gigante, B. (Bruna), Gottesman, R.F. (Rebecca), Grant, G.B. (George), Grarup, N. (Niels), Groves, C.J. (Christopher J.), Hassinen, M. (Maija), Have, C.T. (Christian T.), Herder, C. (Christian), Holmen, O.L. (Oddgeir), Hreidarsson, A.B. (Astradur), Humphries, S.E. (Steve E.), Hunter, D.J. (David J.), Jackson, A.U. (Anne), Jonsson, A. (Anna), Jørgensen, M.E. (Marit E.), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Kerrison, N.D. (Nicola D.), Kinnunen, L. (Leena), Klopp, N. (Norman), Kong, A. (Augustine), Kovacs, P. (Peter), Kraft, P. (Peter), Kravic, J. (Jasmina), Langford, C. (Cordelia), Leander, K. (Karin), Liang, L. (Liming), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia M.), Lindholm, B. (Bengt), Linneberg, A. (Allan), Liu, C.-T. (Ching-Ti), Lobbens, S. (Stéphane), Luan, J. (Jian'fan), Lyssenko, V. (Valeriya), Männistö, S. (Satu), McLeod, O. (Olga), Meyer, J. (Jobst), Mihailov, E. (Evelin), Mirza, G. (Ghazala), Mühleisen, T.W. (Thomas), Müller-Nurasyid, M. (Martina), Navarro, C. (Carmen), Nöthen, M.M. (Markus), Oskolkov, N.N. (Nikolay N.), Owen, K.R. (Katharine), Palli, D. (Domenico), Pechlivanis, S. (Sonali), Peltonen, L. (Leena Johanna), Perry, J.R.B. (John), Platou, C.P. (Carl), Roden, M. (Michael), Ruderfer, D. (Douglas), Rybin, D. (Denis), Van Der Schouw, Y.T. (Yvonne T.), Sennblad, B. (Bengt), Sigurosson, G. (Gunnar), Stancáková, A. (Alena), Steinbach, D., Storm, P. (Petter), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Sun, Q., Thorand, B. (Barbara), Tikkanen, E. (Emmi), Tönjes, A. (Anke), Trakalo, J. (Joseph), Tremoli, E. (Elena), Tuomi, T. (Tiinamaija), Wennauer, R. (Roman), Wiltshire, S. (Steven), Wood, A.R. (Andrew), Zeggini, E. (Eleftheria), Dunham, I. (Ian), Birney, E. (Ewan), Pasquali, L. (Lorenzo), Ferrer, J. (Jorge), Loos, R.J.F. (Ruth), Dupuis, J. (Josée), Florez, J.C. (Jose), Boerwinkle, E.A. (Eric), Pankow, J.S. (James), Duijn, C.M. (Cornelia) van, Sijbrands, E.J.G. (Eric), Meigs, J.B. (James B.), Hu, F.B. (Frank), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Stumvoll, M. (Michael), Pedersen, N.L. (Nancy L.), Lind, L. (Lars), Keinanen-Kiukaanniemi, S. (Sirkka), Korpi-Hyövälti, E. (Eeva), Saaristo, T. (Timo), Saltevo, J. (Juha), Kuusisto, J. (Johanna), Laakso, M. (Markku), Metspalu, A. (Andres), Erbel, R. (Raimund), Jöckel, K.-H. (Karl-Heinz), Moebus, S. (Susanne), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Ingelsson, E. (Erik), Boehm, B.O. (Bernhard), Bergman, R.N. (Richard N.), Collins, F.S. (Francis S.), Mohlke, K.L. (Karen L.), Koistinen, H. (Heikki), Tuomilehto, J. (Jaakko), Hveem, K. (Kristian), Njølstad, I. (Inger), Deloukas, P. (Panagiotis), Donnelly, P.J. (Peter J.), Frayling, T.M. (Timothy), Hattersley, A.T. (Andrew), Faire, U. (Ulf) de, Hamsten, A. (Anders), Illig, T. (Thomas), Peters, A. (Annette), Cauchi, S. (Stephane), Sladek, R. (Rob), Froguel, P. (Philippe), Hansen, T. (Torben), Pedersen, O. (Oluf), Morris, A.D. (Andrew), Palmer, C.N.A. (Collin N. A.), Kathiresan, S. (Sekar), Melander, O. (Olle), Nilsson, P.M. (Peter M.), Groop, L. (Leif), Barroso, I.E. (Inês), Langenberg, C. (Claudia), Wareham, N.J. (Nicholas J.), O'Callaghan, C.A. (Christopher A.), Gloyn, A.L. (Anna), Altshuler, D. (David), Boehnke, M. (Michael), Teslovich, T.M. (Tanya M.), McCarthy, M.I. (Mark), and Morris, A.P. (Andrew)
Abstract: We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
Published: 2015
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23. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author: Winkler, TW, Justice, AE, Graff, M, Barata, L, Feitosa, MF, Chu, S, Czajkowski, J, Esko, T, Fall, T, Kilpelainen, TO, Lu, YC, Magi, R, Mihailov, E, Pers, TH, Rueger, S, Teumer, A, Ehret, GB, Ferreira, T, Heard-Costa, NL, Karjalainen, J, Lagou, V, Mahajan, A, Neinast, MD, Prokopenko, I, Simino, J, Teslovich, TM, Jansen, R, Westra, HJ, White, CC, Absher, D, Ahluwalia, TS, Ahmad, Shahzad, Albrecht, E, Alves, AC, Bragg-Gresham, JL, de Craen, AJM, Bis, JC, Bonnefond, A, Boucher, G, Cadby, G, Cheng, YC, Chiang, CWK, Delgado, G, Demirkan, Ayse, Dueker, N, Eklund, N, Eiriksdottir, G, Eriksson, J, Feenstra, B, Fischer, K (Kirsten), Frau, F, Galesloot, TE, Geller, F, Goel, A, Gorski, M, Grammer, TB, Gustafsson, S, Haitjema, S, Hottenga, JJ (Jouke Jan), Huffman, JE, Jackson, AU, Jacobs, KB, Johansson, A, Kaakinen, M, Kleber, ME, Lahti, J, Leach, IM, Lehne, B, Liu, YF, Lo, KS, Lorentzon, M, Luan, J, Madden, PAF, Mangino, M, McKnight, B, Medina Gomez, Maria, Monda, KL, Montasser, ME, Muller, G, Muller-Nurasyid, M, Nolte, IM (Ilja), Panoutsopoulou, K, Pascoe, L, Paternoster, L, Rayner, NW, Renstrom, F, Rizzi, F, Rose, LM, Ryan, KA, Salo, P, Sanna, S, Scharnagl, H, Shi, JX, Smith, AV, Southam, L, Stancakova, A, Steinthorsdottir, V, Strawbridge, RJ, Sung, YJ, Tachmazidou, I, Tanaka, T, Thorleifsson, G, Trompet, S, Pervjakova, N, Tyrer, JP, Vandenput, L, Laan, Sander, van der Velde, Nathalie, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N (Niek), Vlachopoulou, E, Waite, LL, Wang, SR, Wang, ZM, Wild, SH, Willenborg, C, Wilson, JF, Wong, A, Yang, Jiaqi, Yengo, L, Yerges-Armstrong, LM, Yu, L, Zhang, WH, Zhao, JH, Andersson, EA, Bakker, SJL, Baldassarre, D, Banasik, K, Barcella, M, Barlassina, C, Bellis, C, Benaglio, P, Blangero, J, Bluher, M, Bonnet, F, Bonnycastle, LL, Boyd, HA, Bruinenberg, M, Buchman, AS, Campbell, H, Chen, YDI, Chines, PS, Claudi-Boehm, S, Cole, J, Collins, FS, de Geus, EJC, de Groot, LCPGM (Lisette), Dimitriou, M, Duan, J, Enroth, S, Eury, E, Farmaki, AE, Forouhi, NG, Friedrich, N, Gejman, PV, Gigante, B, Glorioso, N, Go, AS, Gottesman, O, Grassler, J, Grallert, H, Grarup, N, Gu, YM, Broer, Linda, Ham, Annelies, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Heath, AC, Henders, AK, Hernandez, D, Hillege, H, Holmen, O, Hovingh, KG, Hui, J, Husemoen, LL, Hutri-Kahonen, N, Hysi, PG, Illig, T, De Jager, PL, Jalilzadeh, S, Jorgensen, T, Jukema, JW, Juonala, M, Kanoni, S, Karaleftheri, M, Khaw, KT, Kinnunen, L, Kittner, SJ, Koenig, W, Kolcic, I, Kovacs, P, Krarup, NT, Kratzer, W, Kruger, J, Kuh, D, Kumari, M, Kyriakou, T, Langenberg, C, Lannfelt, L, Lanzani, C, Lotay, V, Launer, LJ (Lenore), Leander, K, Lindstrom, J, Linneberg, A, Liu, YP, Lobbens, S, Luben, R, Lyssenko, V, Mannisto, S, Magnusson, PK, McArdle, WL, Menni, C, Merger, S, Milani, L, Montgomery, GW, Morris, AP, Narisu, N, Nelis, M, Ong, KK, Palotie, A, Perusse, L, Pichler, I, Pilia, MG, Pouta, A, Rheinberger, M, Ribel-Madsen, R, Richards, M, Rice, KM, Rice, TK, Rivolta, C, Salomaa, V, Sanders, AR, Sarzynski, MA, Scholtens, s, Scott, RA, Scott, WR, Sebert, S, Sengupta, S, Sennblad, B, Seufferlein, T, Silveira, A, Slagboom, PE (Eline), Smit, JH, Sparso, TH, Stirrups, K, Stolk, RP (Ronald), Stringham, HM, Swertz, MA, Swift, AJ, Syvanen, AC, Tan, ST, Thorand, B, Tonjes, A, Tremblay, A, Tsafantakis, E, van der Most, PJ, Volker, U, Vohl, MC, Vonk, JM, Waldenberger, M, Walker, RW, Wennauer, R, Widen, E, Willemsen, G, Wilsgaard, T, Wright, AF, Zillikens, M.C., Boon - van Dijk, Suzanne, Schoor, NM, Asselbergs, FW, de Bakker, PIW, Beckmann, JS, Beilby, J, Bennett, DA, Bergman, RN, Bergmann, S, Boger, CA, Boehm, BO, Boerwinkle, E, Boomsma, DI, Bornstein, SR, Bottinger, EP, Bouchard, C, Chambers, JC, Chanock, SJ, Chasman, DI, Cucca, F, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, JG, Evans, DA, de Faire, U, Farrall, M, Ferrucci, L, Ford, I, Franke, L, Franks, PW, Froguel, P, Gansevoort, RT, Gieger, C, Gronberg, H, Gudnason, V, Gyllensten, U, Hall, P, Hamsten, A, van der Harst, P, Hayward, C, Heliovaara, M, Hengstenberg, C, Hicks, AA, Hingorani, A, Hofman, Bert, Hu, F, Huikuri, HV, Hveem, K, James, AL, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Kathiresan, S, Kiemeney, LALM, Kivimaki, M, Knekt, PB, Koistinen, HA, Kooner, JS, Koskinen, S, Kuusisto, J, Maerz, W, Martin, NG, Laakso, M, Lakka, TA, Lehtimaki, T, Lettre, G, Levinson, DF, Lind, L, Lokki, ML, Mantyselka, P, Melbye, M, Metspalu, A, Mitchell, BD, Moll, FL, Murray, JC, Musk, AW, Nieminen, MS, Njolstad, I, Ohlsson, C, Oldehinkel, AJ (A.), Oostra, Ben, Palmer, LJ, Pankow, JS, Pasterkamp, G, Pedersen, NL, Pedersen, O, Penninx, BW, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Psaty, BM, Qi, L, Quertermous, T, Raitakari, OT, Rankinen, T, Rauramaa, R, Ridker, PM, Rioux, JD, Rivadeneira, Fernando, Rotter, JI, Rudan, I, den Ruijter, HM, Saltevo, J, Sattar, N, Schunkert, H, Schwarz, PEH, Shuldiner, AR, Sinisalo, J, Snieder, H, Sorensen, TIA, Spector, TD, Staessen, JA, Stefania, B, Thorsteinsdottir, U, Stumvoll, M, Tardif, JC, Tremoli, E, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Verbeek, ALM, Vermeulen, SH, Viikari, JS, Vitart, V, Volzke, H, Vollenweider, P, Waeber, G, Walker, M, Wallaschofski, H, Wareham, NJ, Watkins, H, Zeggini, E, Chakravarti, A, Clegg, DJ, Cupples, LA, Gordon-Larsen, P, Jaquish, CE, Rao, DC, Abecasis, GR, Assimes, TL, Barroso, I, Berndt, SI, Boehnke, M, Deloukas, P, Fox, CS, Groop, LC, Hunter, DJ, Ingelsson, E, Kaplan, RC, McCarthy, MI, Mohlke, KL, O'Connell, JR, Schlessinger, D, Strachan, DP, Stefansson, K, Duijn, Cornelia, Hirschhorn, JN, Lindgren, CM, Heid, IM, North, KE, Borecki, IB, Kutalik, Z, Loos, RJF, Winkler, TW, Justice, AE, Graff, M, Barata, L, Feitosa, MF, Chu, S, Czajkowski, J, Esko, T, Fall, T, Kilpelainen, TO, Lu, YC, Magi, R, Mihailov, E, Pers, TH, Rueger, S, Teumer, A, Ehret, GB, Ferreira, T, Heard-Costa, NL, Karjalainen, J, Lagou, V, Mahajan, A, Neinast, MD, Prokopenko, I, Simino, J, Teslovich, TM, Jansen, R, Westra, HJ, White, CC, Absher, D, Ahluwalia, TS, Ahmad, Shahzad, Albrecht, E, Alves, AC, Bragg-Gresham, JL, de Craen, AJM, Bis, JC, Bonnefond, A, Boucher, G, Cadby, G, Cheng, YC, Chiang, CWK, Delgado, G, Demirkan, Ayse, Dueker, N, Eklund, N, Eiriksdottir, G, Eriksson, J, Feenstra, B, Fischer, K (Kirsten), Frau, F, Galesloot, TE, Geller, F, Goel, A, Gorski, M, Grammer, TB, Gustafsson, S, Haitjema, S, Hottenga, JJ (Jouke Jan), Huffman, JE, Jackson, AU, Jacobs, KB, Johansson, A, Kaakinen, M, Kleber, ME, Lahti, J, Leach, IM, Lehne, B, Liu, YF, Lo, KS, Lorentzon, M, Luan, J, Madden, PAF, Mangino, M, McKnight, B, Medina Gomez, Maria, Monda, KL, Montasser, ME, Muller, G, Muller-Nurasyid, M, Nolte, IM (Ilja), Panoutsopoulou, K, Pascoe, L, Paternoster, L, Rayner, NW, Renstrom, F, Rizzi, F, Rose, LM, Ryan, KA, Salo, P, Sanna, S, Scharnagl, H, Shi, JX, Smith, AV, Southam, L, Stancakova, A, Steinthorsdottir, V, Strawbridge, RJ, Sung, YJ, Tachmazidou, I, Tanaka, T, Thorleifsson, G, Trompet, S, Pervjakova, N, Tyrer, JP, Vandenput, L, Laan, Sander, van der Velde, Nathalie, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N (Niek), Vlachopoulou, E, Waite, LL, Wang, SR, Wang, ZM, Wild, SH, Willenborg, C, Wilson, JF, Wong, A, Yang, Jiaqi, Yengo, L, Yerges-Armstrong, LM, Yu, L, Zhang, WH, Zhao, JH, Andersson, EA, Bakker, SJL, Baldassarre, D, Banasik, K, Barcella, M, Barlassina, C, Bellis, C, Benaglio, P, Blangero, J, Bluher, M, Bonnet, F, Bonnycastle, LL, Boyd, HA, Bruinenberg, M, Buchman, AS, Campbell, H, Chen, YDI, Chines, PS, Claudi-Boehm, S, Cole, J, Collins, FS, de Geus, EJC, de Groot, LCPGM (Lisette), Dimitriou, M, Duan, J, Enroth, S, Eury, E, Farmaki, AE, Forouhi, NG, Friedrich, N, Gejman, PV, Gigante, B, Glorioso, N, Go, AS, Gottesman, O, Grassler, J, Grallert, H, Grarup, N, Gu, YM, Broer, Linda, Ham, Annelies, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Heath, AC, Henders, AK, Hernandez, D, Hillege, H, Holmen, O, Hovingh, KG, Hui, J, Husemoen, LL, Hutri-Kahonen, N, Hysi, PG, Illig, T, De Jager, PL, Jalilzadeh, S, Jorgensen, T, Jukema, JW, Juonala, M, Kanoni, S, Karaleftheri, M, Khaw, KT, Kinnunen, L, Kittner, SJ, Koenig, W, Kolcic, I, Kovacs, P, Krarup, NT, Kratzer, W, Kruger, J, Kuh, D, Kumari, M, Kyriakou, T, Langenberg, C, Lannfelt, L, Lanzani, C, Lotay, V, Launer, LJ (Lenore), Leander, K, Lindstrom, J, Linneberg, A, Liu, YP, Lobbens, S, Luben, R, Lyssenko, V, Mannisto, S, Magnusson, PK, McArdle, WL, Menni, C, Merger, S, Milani, L, Montgomery, GW, Morris, AP, Narisu, N, Nelis, M, Ong, KK, Palotie, A, Perusse, L, Pichler, I, Pilia, MG, Pouta, A, Rheinberger, M, Ribel-Madsen, R, Richards, M, Rice, KM, Rice, TK, Rivolta, C, Salomaa, V, Sanders, AR, Sarzynski, MA, Scholtens, s, Scott, RA, Scott, WR, Sebert, S, Sengupta, S, Sennblad, B, Seufferlein, T, Silveira, A, Slagboom, PE (Eline), Smit, JH, Sparso, TH, Stirrups, K, Stolk, RP (Ronald), Stringham, HM, Swertz, MA, Swift, AJ, Syvanen, AC, Tan, ST, Thorand, B, Tonjes, A, Tremblay, A, Tsafantakis, E, van der Most, PJ, Volker, U, Vohl, MC, Vonk, JM, Waldenberger, M, Walker, RW, Wennauer, R, Widen, E, Willemsen, G, Wilsgaard, T, Wright, AF, Zillikens, M.C., Boon - van Dijk, Suzanne, Schoor, NM, Asselbergs, FW, de Bakker, PIW, Beckmann, JS, Beilby, J, Bennett, DA, Bergman, RN, Bergmann, S, Boger, CA, Boehm, BO, Boerwinkle, E, Boomsma, DI, Bornstein, SR, Bottinger, EP, Bouchard, C, Chambers, JC, Chanock, SJ, Chasman, DI, Cucca, F, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, JG, Evans, DA, de Faire, U, Farrall, M, Ferrucci, L, Ford, I, Franke, L, Franks, PW, Froguel, P, Gansevoort, RT, Gieger, C, Gronberg, H, Gudnason, V, Gyllensten, U, Hall, P, Hamsten, A, van der Harst, P, Hayward, C, Heliovaara, M, Hengstenberg, C, Hicks, AA, Hingorani, A, Hofman, Bert, Hu, F, Huikuri, HV, Hveem, K, James, AL, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Kathiresan, S, Kiemeney, LALM, Kivimaki, M, Knekt, PB, Koistinen, HA, Kooner, JS, Koskinen, S, Kuusisto, J, Maerz, W, Martin, NG, Laakso, M, Lakka, TA, Lehtimaki, T, Lettre, G, Levinson, DF, Lind, L, Lokki, ML, Mantyselka, P, Melbye, M, Metspalu, A, Mitchell, BD, Moll, FL, Murray, JC, Musk, AW, Nieminen, MS, Njolstad, I, Ohlsson, C, Oldehinkel, AJ (A.), Oostra, Ben, Palmer, LJ, Pankow, JS, Pasterkamp, G, Pedersen, NL, Pedersen, O, Penninx, BW, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Psaty, BM, Qi, L, Quertermous, T, Raitakari, OT, Rankinen, T, Rauramaa, R, Ridker, PM, Rioux, JD, Rivadeneira, Fernando, Rotter, JI, Rudan, I, den Ruijter, HM, Saltevo, J, Sattar, N, Schunkert, H, Schwarz, PEH, Shuldiner, AR, Sinisalo, J, Snieder, H, Sorensen, TIA, Spector, TD, Staessen, JA, Stefania, B, Thorsteinsdottir, U, Stumvoll, M, Tardif, JC, Tremoli, E, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Verbeek, ALM, Vermeulen, SH, Viikari, JS, Vitart, V, Volzke, H, Vollenweider, P, Waeber, G, Walker, M, Wallaschofski, H, Wareham, NJ, Watkins, H, Zeggini, E, Chakravarti, A, Clegg, DJ, Cupples, LA, Gordon-Larsen, P, Jaquish, CE, Rao, DC, Abecasis, GR, Assimes, TL, Barroso, I, Berndt, SI, Boehnke, M, Deloukas, P, Fox, CS, Groop, LC, Hunter, DJ, Ingelsson, E, Kaplan, RC, McCarthy, MI, Mohlke, KL, O'Connell, JR, Schlessinger, D, Strachan, DP, Stefansson, K, Duijn, Cornelia, Hirschhorn, JN, Lindgren, CM, Heid, IM, North, KE, Borecki, IB, Kutalik, Z, and Loos, RJF
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men <= 50y, men > 50y, women <= 50y, women > 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap
Published: 2015

24. Once-yearly zoledronic acid and days of disability, bed rest, and back pain: Randomized, controlled HORIZON Pivotal Fracture Trial

Author: Cauley, J. a., Dennis, Black, Steven, Boonen, Cummings, Steven R., Peter, Mesenbrink, Lisa, Palermo, Zulema, Man, Peyman, Hadji, Horizon Pivotal Fracture Group Horowitz, Reid Ir Z., Orloff, J., Black, D., Cummings, S., Delmas, P., Eastell, R., Reid, Ian R., Boonen, S., Cauley, J., Cosman, F., Lakatos, P., Leung, P. c., Man, Z., Lau, E., Jasqui, S., Mautalen, C., Rosario Jansen, T., Caminis, J., Eriksen, E. f., Mesenbrink, P., Raisz, L., Bauer, P., Compston, J., Demets, D., Hirschberg, R., Johnell, O., Ralston, S., Wallace, R., Farkough, M., Flood, M., Bauer, D., Palermo, L., Lang, T., Kerzberg, E., Ridruejo, M., Tate, G., Velasco, J., Hooper, M., Kotowicz, M., Nash, P., Prince, R., Roberts, A., Sambrook, P., Dobnig, H., Finkenstedt, G., Hoefle, G., Klaushofer, K., Pecherstorfer, M., Peichl, P., Body, J., Devogelaer, J. p., Geusens, P., Kaufman, J., Brenol, J., Kochen, J., Lederman, R., Radominski, S., Szejnfeld, V., Zerbini, C., Adachi, J., Brown, J., Choquette, D., Hanley, D., Josse, R., Kendler, D., Kremer, R., Morin, F., Olszynski, W., Papaioannou, A., Kinyuen, C., Chen, B., Lin, S., Casas, N., Chalem, M., Jaller, J., Molina, J., Aro, H., Heikkinen, J., Kroger, H., Makinen, L., Saltevo, J., Salmi, J., Valimaki, M., Benhamou, C. l., Fardellone, P., Werhya, G., Allolio, B., Felsenberg, D., Happ, J., Hartard, M., Hensen, J., Kaps, P., Kekow, J., Moericke, R., Ortloff, B., Schneider, P., Wassenberg, S., Balogh, A., Gomor, B., Hidvegi, T., Koranyi, L., Poor, G., Tulassay, Z., Pollak, R. d., Eshed, V., Foldes, A. j., Ish Shalom, S., Vered, I., Weiss, M., Adami, S., Barone, A., Bianchi, G., Giannini, S., Isaia, G. c., Luisetto, G., Minisola, Salvatore, Molea, N., Nuti, R., Ortolani, S., Passeri, M., Rubinacci, A., Seriolo, B., Sinigaglia, L., Choi, W. h., Kang, M. i., Kim, G. s., Kim, H. s., Kim, Y. k., Lim, S. k., Son, H. y., Yoon, H. k., Abud, C., Garcia, P., Ochoa, L., Orozco, J., Santos, J., Reid, I., Elle, S., Halse, J., Høiseth, A., Olav, H., Røed, H. i., Skag, A., Stakkestad, J., Syversen, U., Badurski, J., Czerwinski, E., Lorenc, R., Marcinowska Suchowierska, E., Sawicki, A., Supronik, J., Ailamazyan, E., Benevolenskaya, L., Dreval, A., Dvoretsky, L., Dyomina, R., Mazurov, V., Melnichenko, G., Mkrtoumyan, A., Orlov Morozov, A., Ostroumova, O., Pikhlak, E., Shemerovskaya, T., Shostak, N., Skripnikova, I., Smetnik, V., Tsyrlina, E., Usova, G., Zalevskaya, A., Zazerskaya, I., Zotkin, E., Ljunggren, O., Lofgren, J., Palmer, M., Saaf, M., Stenstrom, M., Hasler, P., Lamy, O., Lippuner, K., Merlin, C., Rizzoli, R., Theiler, R., Tyndall, A., Uebelhart, D., Chen, J. f., Chen, P. q., Chin, L. s., Hwang, J. s., Yang, T. s., Jirapinyo, M., Sattaya, R., Sriussadaporn, S., Supasin, S., Taechakraichana, N., Wilawan, K., Donnachie, H., Fraser, W., Mclellan, A., Reid, D., Abruzzo, J., Ackerman, R., Adler, R., Aloia, J., Birbara, C., Bode, B., Bone, H., Brandon, D., Dionne, D., Jr Downs, R., Dreyfus, J., Elinoff, V., Emkey, R., Fanciullo, J., Fiske, D., Genaro, P., Gollapudi, M., Gordon, R., Hennessey, J., Howard, P., Johnson, K., Johnston, C., Kagan, R., Kafka, S., Kaine, J., Klein, T., Koltun, W., Leboff, M., Levine, B., Lewiecki, E. m., Lewis, C. e., Licata, A., Lillestol, M., Lubin, B., Malamet, R., Mangione, A., Matkovic, V., Mehta, D., Miller, P., Miller, S., Murphy, F. t., Nattrass, S., Podlecki, D., Recknor, C., Rosen, C., Rowe, D., Rude, R., Schnitzer, T., Sherrer, Y., Silverman, S., Stephenson, K., Troupin, B., Tucci, J., Villareal, R., Watts, N., Weinstein, R., Weitz, M., and White, R.
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Osteoporosis, Bed rest, Placebo, Drug Administration Schedule, Article, law.invention, postmenopausal osteoporosis, zoledronic acid, Randomized controlled trial, Risk Factors, law, Back pain, disability, fracture, Internal medicine, Prevalence, Humans, Medicine, Disabled Persons, Orthopedics and Sports Medicine, Probability, Bone Density Conservation Agents, Diphosphonates, business.industry, Imidazoles, medicine.disease, Back Pain, Female, Multivariate Analysis, Spinal Fractures, Bed Rest, Low back pain, Surgery, Zoledronic acid, Relative risk, medicine.symptom, business, medicine.drug
Abstract: The objective of this study was to determine the effect of once-yearly zoledronic acid on the number of days of back pain and the number of days of disability (ie, limited activity and bed rest) owing to back pain or fracture in postmenopausal women with osteoporosis. This was a multicenter, randomized, double-blind, placebo-controlled trial in 240 clinical centers in 27 countries. Participants included 7736 postmenopausal women with osteoporosis. Patients were randomized to receive either a single 15-minute intravenous infusion of zoledronic acid (5 mg) or placebo at baseline, 12 months, and 24 months. The main outcome measures were self-reported number of days with back pain and the number of days of limited activity and bed rest owing to back pain or a fracture, and this was assessed every 3 months over a 3-year period. Our results show that although the incidence of back pain was high in both randomized groups, women randomized to zoledronic acid experienced, on average, 18 fewer days of back pain compared with placebo over the course of the trial (p = .0092). The back pain among women randomized to zoledronic acid versus placebo resulted in 11 fewer days of limited activity (p = .0017). In Cox proportional-hazards models, women randomized to zoledronic acid were about 6% less likely to experience 7 or more days of back pain [relative risk (RR) = 0.94, 95% confidence interval (CI) 0.90–0.99] or limited activity owing to back pain (RR = 0.94, 95% CI 0.87–1.00). Women randomized to zoledronic acid were significantly less likely to experience 7 or more bed-rest days owing to a fracture (RR = 0.58, 95% CI 0.47–0.72) and 7 or more limited-activity days owing to a fracture (RR = 0.67, 95% CI 0.58–0.78). Reductions in back pain with zoledronic acid were independent of incident fracture. Our conclusion is that in women with postmenopausal osteoporosis, a once-yearly infusion with zoledronic acid over a 3-year period significantly reduced the number of days that patients reported back pain, limited activity owing to back pain, and limited activity and bed rest owing to a fracture.
Published: 2011

25. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Author: Mahajan, A, Go, MJ, Zhang, W, Below, JE, Gaulton, KJ, Ferreira, T, Horikoshi, M, Johnson, AD, Ng, MCY, Prokopenko, I, Saleheen, D, Wang, X, Zeggini, E, Abecasis, GR, Adair, LS, Almgren, P, Atalay, M, Aung, T, Baldassarre, D, Balkau, B, Bao, Y, Barnett, AH, Barroso, I, Basit, A, Been, LF, Beilby, J, Bell, GI, Benediktsson, R, Bergman, RN, Boehm, BO, Boerwinkle, E, Bonnycastle, LL, Burtt, N, Cai, Q, Campbell, H, Carey, J, Cauchi, S, Caulfield, M, Chan, JCN, Chang, L-C, Chang, T-J, Chang, Y-C, Charpentier, G, Chen, C-H, Chen, H, Chen, Y-T, Chia, K-S, Chidambaram, M, Chines, PS, Cho, NH, Cho, YM, Chuang, L-M, Collins, FS, Cornelis, MC, Couper, DJ, Crenshaw, AT, van Dam, RM, Danesh, J, Das, D, de Faire, U, Dedoussis, G, Deloukas, P, Dimas, AS, Dina, C, Doney, ASF, Donnelly, PJ, Dorkhan, M, van Duijn, C, Dupuis, J, Edkins, S, Elliott, P, Emilsson, V, Erbel, R, Eriksson, JG, Escobedo, J, Esko, T, Eury, E, Florez, JC, Fontanillas, P, Forouhi, NG, Forsen, T, Fox, C, Fraser, RM, Frayling, TM, Froguel, P, Frossard, P, Gao, Y, Gertow, K, Gieger, C, Gigante, B, Grallert, H, Grant, GB, Groop, LC, Groves, CJ, Grundberg, E, Guiducci, C, Hamsten, A, Han, B-G, Hara, K, Hassanali, N, Hattersley, AT, Hayward, C, Hedman, AK, Herder, C, Hofman, A, Holmen, OL, Hovingh, K, Hreidarsson, AB, Hu, C, Hu, FB, Hui, J, Humphries, SE, Hunt, SE, Hunter, DJ, Hveem, K, Hydrie, ZI, Ikegami, H, Illig, T, Ingelsson, E, Islam, M, Isomaa, B, Jackson, AU, Jafar, T, James, A, Jia, W, Joeckel, K-H, Jonsson, A, Jowett, JBM, Kadowaki, T, Kang, HM, Kanoni, S, Kao, WHL, Kathiresan, S, Kato, N, Katulanda, P, Keinanen-Kiukaanniemi, SM, Kelly, AM, Khan, H, Khaw, K-T, Khor, C-C, Kim, H-L, Kim, S, Kim, YJ, Kinnunen, L, Klopp, N, Kong, A, Korpi-Hyovalti, E, Kowlessur, S, Kraft, P, Kravic, J, Kristensen, MM, Krithika, S, Kumar, A, Kumate, J, Kuusisto, J, Kwak, SH, Laakso, M, Lagou, V, Lakka, TA, Langenberg, C, Langford, C, Lawrence, R, Leander, K, Lee, J-M, Lee, NR, Li, M, Li, X, Li, Y, Liang, J, Liju, S, Lim, W-Y, Lind, L, Lindgren, CM, Lindholm, E, Liu, C-T, Liu, JJ, Lobbens, S, Long, J, Loos, RJF, Lu, W, Luan, J, Lyssenko, V, Ma, RCW, Maeda, S, Maegi, R, Mannisto, S, Matthews, DR, Meigs, JB, Melander, O, Metspalu, A, Meyer, J, Mirza, G, Mihailov, E, Moebus, S, Mohan, V, Mohlke, KL, Morris, AD, Muehleisen, TW, Mueller-Nurasyid, M, Musk, B, Nakamura, J, Nakashima, E, Navarro, P, Peng-Keat, N, Nica, AC, Nilsson, PM, Njolstad, I, Noethen, MM, Ohnaka, K, Ong, TH, Owen, KR, Palmer, CNA, Pankow, JS, Park, KS, Parkin, M, Pechlivanis, S, Pedersen, NL, Peltonen, L, Perry, JRB, Peters, A, Pinidiyapathirage, JM, Platou, CGP, Potter, S, Price, JF, Qi, L, Radha, V, Rallidis, L, Rasheed, A, Rathmann, W, Rauramaa, R, Raychaudhuri, S, Rayner, NW, Rees, SD, Rehnberg, E, Ripatti, S, Robertson, N, Roden, M, Rossin, EJ, Rudan, I, Rybin, D, Saaristo, TE, Salomaa, V, Saltevo, J, Samuel, M, Sanghera, DK, Saramies, J, Scott, J, Scott, LJ, Scott, RA, Segre, AV, Sehmi, J, Sennblad, B, Shah, N, Shah, S, Shera, AS, Shu, XO, Shuldiner, AR, Sigurdsson, G, Sijbrands, E, Silveira, A, Sim, X, Sivapalaratnam, S, Small, KS, So, WY, Stancakova, A, Stefansson, K, Steinbach, G, Steinthorsdottir, V, Stirrups, K, Strawbridge, RJ, Stringham, HM, Sun, Q, Suo, C, Syvanen, A-C, Takayanagi, R, Takeuchi, F, Tay, WT, Teslovich, TM, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Tikkanen, E, Trakalo, J, Tremoli, E, Trip, MD, Tsai, FJ, Tuomi, T, Tuomilehto, J, Uitterlinden, AG, Valladares-Salgado, A, Vedantam, S, Veglia, F, Voight, BF, Wang, C, Wareham, NJ, Wennauer, R, Wickremasinghe, AR, Wilsgaard, T, Wilson, JF, Wiltshire, S, Winckler, W, Wong, TY, Wood, AR, Wu, J-Y, Wu, Y, Yamamoto, K, Yamauchi, T, Yang, M, Yengo, L, Yokota, M, Young, R, Zabaneh, D, Zhang, F, Zhang, R, Zheng, W, Zimmet, PZ, Altshuler, D, Bowden, DW, Cho, YS, Cox, NJ, Cruz, M, Hanis, CL, Kooner, J, Lee, J-Y, Seielstad, M, Teo, YY, Boehnke, M, Parra, EJ, Chambers, JC, Tai, ES, McCarthy, MI, Morris, AP, Mahajan, A, Go, MJ, Zhang, W, Below, JE, Gaulton, KJ, Ferreira, T, Horikoshi, M, Johnson, AD, Ng, MCY, Prokopenko, I, Saleheen, D, Wang, X, Zeggini, E, Abecasis, GR, Adair, LS, Almgren, P, Atalay, M, Aung, T, Baldassarre, D, Balkau, B, Bao, Y, Barnett, AH, Barroso, I, Basit, A, Been, LF, Beilby, J, Bell, GI, Benediktsson, R, Bergman, RN, Boehm, BO, Boerwinkle, E, Bonnycastle, LL, Burtt, N, Cai, Q, Campbell, H, Carey, J, Cauchi, S, Caulfield, M, Chan, JCN, Chang, L-C, Chang, T-J, Chang, Y-C, Charpentier, G, Chen, C-H, Chen, H, Chen, Y-T, Chia, K-S, Chidambaram, M, Chines, PS, Cho, NH, Cho, YM, Chuang, L-M, Collins, FS, Cornelis, MC, Couper, DJ, Crenshaw, AT, van Dam, RM, Danesh, J, Das, D, de Faire, U, Dedoussis, G, Deloukas, P, Dimas, AS, Dina, C, Doney, ASF, Donnelly, PJ, Dorkhan, M, van Duijn, C, Dupuis, J, Edkins, S, Elliott, P, Emilsson, V, Erbel, R, Eriksson, JG, Escobedo, J, Esko, T, Eury, E, Florez, JC, Fontanillas, P, Forouhi, NG, Forsen, T, Fox, C, Fraser, RM, Frayling, TM, Froguel, P, Frossard, P, Gao, Y, Gertow, K, Gieger, C, Gigante, B, Grallert, H, Grant, GB, Groop, LC, Groves, CJ, Grundberg, E, Guiducci, C, Hamsten, A, Han, B-G, Hara, K, Hassanali, N, Hattersley, AT, Hayward, C, Hedman, AK, Herder, C, Hofman, A, Holmen, OL, Hovingh, K, Hreidarsson, AB, Hu, C, Hu, FB, Hui, J, Humphries, SE, Hunt, SE, Hunter, DJ, Hveem, K, Hydrie, ZI, Ikegami, H, Illig, T, Ingelsson, E, Islam, M, Isomaa, B, Jackson, AU, Jafar, T, James, A, Jia, W, Joeckel, K-H, Jonsson, A, Jowett, JBM, Kadowaki, T, Kang, HM, Kanoni, S, Kao, WHL, Kathiresan, S, Kato, N, Katulanda, P, Keinanen-Kiukaanniemi, SM, Kelly, AM, Khan, H, Khaw, K-T, Khor, C-C, Kim, H-L, Kim, S, Kim, YJ, Kinnunen, L, Klopp, N, Kong, A, Korpi-Hyovalti, E, Kowlessur, S, Kraft, P, Kravic, J, Kristensen, MM, Krithika, S, Kumar, A, Kumate, J, Kuusisto, J, Kwak, SH, Laakso, M, Lagou, V, Lakka, TA, Langenberg, C, Langford, C, Lawrence, R, Leander, K, Lee, J-M, Lee, NR, Li, M, Li, X, Li, Y, Liang, J, Liju, S, Lim, W-Y, Lind, L, Lindgren, CM, Lindholm, E, Liu, C-T, Liu, JJ, Lobbens, S, Long, J, Loos, RJF, Lu, W, Luan, J, Lyssenko, V, Ma, RCW, Maeda, S, Maegi, R, Mannisto, S, Matthews, DR, Meigs, JB, Melander, O, Metspalu, A, Meyer, J, Mirza, G, Mihailov, E, Moebus, S, Mohan, V, Mohlke, KL, Morris, AD, Muehleisen, TW, Mueller-Nurasyid, M, Musk, B, Nakamura, J, Nakashima, E, Navarro, P, Peng-Keat, N, Nica, AC, Nilsson, PM, Njolstad, I, Noethen, MM, Ohnaka, K, Ong, TH, Owen, KR, Palmer, CNA, Pankow, JS, Park, KS, Parkin, M, Pechlivanis, S, Pedersen, NL, Peltonen, L, Perry, JRB, Peters, A, Pinidiyapathirage, JM, Platou, CGP, Potter, S, Price, JF, Qi, L, Radha, V, Rallidis, L, Rasheed, A, Rathmann, W, Rauramaa, R, Raychaudhuri, S, Rayner, NW, Rees, SD, Rehnberg, E, Ripatti, S, Robertson, N, Roden, M, Rossin, EJ, Rudan, I, Rybin, D, Saaristo, TE, Salomaa, V, Saltevo, J, Samuel, M, Sanghera, DK, Saramies, J, Scott, J, Scott, LJ, Scott, RA, Segre, AV, Sehmi, J, Sennblad, B, Shah, N, Shah, S, Shera, AS, Shu, XO, Shuldiner, AR, Sigurdsson, G, Sijbrands, E, Silveira, A, Sim, X, Sivapalaratnam, S, Small, KS, So, WY, Stancakova, A, Stefansson, K, Steinbach, G, Steinthorsdottir, V, Stirrups, K, Strawbridge, RJ, Stringham, HM, Sun, Q, Suo, C, Syvanen, A-C, Takayanagi, R, Takeuchi, F, Tay, WT, Teslovich, TM, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Tikkanen, E, Trakalo, J, Tremoli, E, Trip, MD, Tsai, FJ, Tuomi, T, Tuomilehto, J, Uitterlinden, AG, Valladares-Salgado, A, Vedantam, S, Veglia, F, Voight, BF, Wang, C, Wareham, NJ, Wennauer, R, Wickremasinghe, AR, Wilsgaard, T, Wilson, JF, Wiltshire, S, Winckler, W, Wong, TY, Wood, AR, Wu, J-Y, Wu, Y, Yamamoto, K, Yamauchi, T, Yang, M, Yengo, L, Yokota, M, Young, R, Zabaneh, D, Zhang, F, Zhang, R, Zheng, W, Zimmet, PZ, Altshuler, D, Bowden, DW, Cho, YS, Cox, NJ, Cruz, M, Hanis, CL, Kooner, J, Lee, J-Y, Seielstad, M, Teo, YY, Boehnke, M, Parra, EJ, Chambers, JC, Tai, ES, McCarthy, MI, and Morris, AP
Abstract: To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
Published: 2014

26. Fenofibrate intervention and event lowering in diabetes (FIELD) study: baseline characteristics and short-term effects of fenofibrate [ISRCTN64783481]

Author: Scott, R, Best, J, Forder, P, Taskinen, M-R, Simes, J, Barter, P, Keech, A, Colman, P, D'Emden, M, Davis, T, Drury, P, Ehnholm, C, Glasziou, P, Hunt, D, Kesaniemi, YA, Laakso, M, Simes, RJ, Sullivan, D, Whiting, M, Ansquer, J-C, Fraitag, B, Anderson, N, Hankey, G, Lehto, S, Mann, S, Romo, M, Li, LP, Hennekens, C, MacMahon, S, Pocock, S, Tonkin, A, Wilhelmsen, L, Akauola, H, Alford, F, Beinart, I, Bohra, S, Boyages, S, Connor, H, Darnell, D, Davoren, P, Lepre, F, De Looze, F, Duffield, A, Fassett, R, Flack, J, Fulcher, G, Grant, S, Hamwood, S, Harmelin, D, Jackson, R, Jeffries, W, Kamp, M, Kritharides, L, Mahar, L, McCann, V, McIntyre, D, Moses, R, Newnham, H, Nicholson, G, O'Brien, R, Park, K, Petrovsky, N, Phillips, P, Pinn, G, Simmons, D, Stanton, K, Stuckey, B, Sullivan, DR, Suranyi, M, Suthers, M, Tan, Y, Templer, M, Topliss, D, Waites, JH, Watts, G, Welborn, T, Wyndham, R, Haapamaki, H, Kesaniemi, A, Lahtela, J, Levanen, H, Saltevo, J, Sodervik, H, Taskinen, M, Vanhala, M, Baker, J, Burton, A, Dixon, P, Doran, J, Dunn, P, Graham, N, Hamer, A, Hedley, J, Lloyd, J, Manning, P, McPherson, I, Morris, S, Renner, C, Smith, R, Wackrow, M, Young, S, Alard, F, Alcoe, J, Allan, C, Amerena, J, Anderson, R, Arnold, N, Arsov, T, Ashby, D, Atkinson, C, Badhni, L, Balme, M, Barton, D, Batrouney, B, Beare, C, Beattie, T, Beggs, J, Bendall, C, Benz, A, Bond, A, Bradfield, R, Bradshaw, J, Brearley, S, Bruce, D, Burgess, J, Butler, J, Callary, M, Campbell, J, Chambers, K, Chow, J, Chow, S, Ciszek, K, Clifton, P, Clifton-Bligh, P, Clowes, V, Coates, P, Cocks, C, Cole, S, Colquhoun, D, Correcha, M, Costa, B, Coverdale, S, Croft, M, Crowe, J, Dal Sasso, S, Davis, W, Dunn, J, Edwards, S, Elder, R, El-Kaissi, S, Emery, L, England, M, Farouque, O, Fernandez, M, Fitzpatrick, B, Francis, N, Freeman, P, Fuller, A, Gale, D, Gaylard, V, Gillzan, C, Glatthaar, C, Goddard, J, Grange, V, Greenaway, T, Griffin, J, Grogan, A, Guha, S, Gustafson, J, Hamblin, PS, Hannay, T, Hardie, C, Harper, A, Hartl, G, Harvey, A, Havlin, S, Haworth, K, Hay, P, Hay, L, Heenan, B, Hesketh, R, Heyworth, A, Hines, M, Hockings, G, Hodge, A, Hoffman, L, Hoskin, L, Howells, M, Hunt, A, Inder, W, Jackson, D, Jovanovska, A, Kearins, K, Kee, P, Keen, J, Kilpatrick, D, Kindellan, J, Kingston-Ray, M, Kotowicz, M, Lassig, A, Layton, M, Lean, S, Lim, E, Long, F, Lucas, L, Ludeman, D, Ludeman-Robertson, C, Lyall, M, Lynch, L, Maddison, C, Malkus, B, Marangou, A, Margrie, F, Matthiesson, K, Matthiesson, J, Maxwell, S, McCarthy, K, McElduff, A, Mckee, H, McKenzie, J, McLachan, K, McNair, P, Meischke, M, Miller, AMC, Morrison, B, Morton, A, Mossman, W, Mowat, A, Muecke, J, Murie, P, Murray, S, Nadorp, P, Nair, S, Nairn, J, Nankervis, A, Narayan, K, Nattrass, N, Ngui, J, Nicholls, S, Nicholls, V, Nye, JA, Nye, E, O'Neal, D, O'Neill, M, O'Rourke, S, Pearse, J, Pearson, C, Phillips, J, Pittis, L, Playford, D, Porter, L, Portley, R, Powell, M, Preston, C, Pringle, S, Quinn, WA, Raffaele, J, Ramnath, G, Ramsden, J, Richtsteiger, D, Roffe, S, Rosen, S, Ross, G, Ross, Z, Rowe, J, Rumble, D, Ryan, S, Sansom, J, Seymour, C, Shanahan, E, Shelly, S, Shepherd, J, Sherman, G, Siddall, R, Silva, D, Simmons, S, Simpson, R, Sinha, A, Slobodniuk, R, Smith, M, Smith, P, Smith, S, Smith-Orr, V, Snow, J, Socha, L, Stack, T, Steed, K, Steele, K, Stephensen, J, Stevens, P, Stewart, G, Stewart, R, Strakosch, C, Sullivan, M, Sunder, S, Sunderland, J, Tapp, E, Taylor, J, Thorn, D, Tolley, A, Torpy, D, Truran, G, Turner, F, Turner, J, Van de Velde, J, Varley, S, Wallace, J, Walsh, J, Walshe, J, Ward, G, Watson, B, Watson, J, Webb, A, Werner, F, White, E, Whitehouse, A, Whitehouse, N, Wigg, S, Wilkinson, J, Wilmshurst, E, Wilson, D, Wittert, G, Wong, B, Wong, M, Worboys, S, Wright, S, Wu, S, Yarker, J, Yeo, M, Young, K, Youssef, J, Yuen, R, Zeimer, H, Ziffer, RW, Aura, A, Friman, A, Hanninen, J, Henell, J, Hyvarinen, N, Ikonen, M, Itkonen, A, Jappinen, J, Jarva, A, Jerkkola, T, Jokinen, V, Juutilainen, J, Kahkonen, H, Kangas, T, Karttunen, M, Kauranen, P, Kortelainen, S, Koukkunen, H, Kumpulainen, L, Laitinen, T, Laitinen, M, Lehto, R, Leinonen, E, Lindstron-Karjalainen, M, Lumiaho, A, Makela, J, Makinen, K, Mannermaa, L, Mard, T, Miettinen, J, Naatti, V, Paavola, S, Parssinen, N, Ripatti, J, Ruotsalainen, S, Salo, A, Siiskonen, M, Soppela, A, Starck, J, Suonranta, I, Ukkola, L, Valli, K, Virolainen, J, Allan, P, Arnold, W, Bagg, W, Balfour, K, Ball, T, Ballantine, B, Ballantyne, C, Barker, C, Bartley, F, Berry, E, Braatvedt, G, Campbell, A, Clarke, T, Clarke, R, Claydon, A, Clayton, S, Cresswell, P, Cutfield, R, Daffurn, J, Delahunt, J, Dissnayake, A, Eagleton, C, Ferguson, C, Florkowski, C, Fry, D, Giles, P, Gluyas, M, Grant, C, Guile, P, Guolo, M, Hale, P, Hammond, M, Healy, P, Hills, M, Hinge, J, Holland, J, Hyne, B, Ireland, A, Johnstone, A, Jones, S, Kerr, G, Kerr, K, Khant, M, Krebs, J, Law, L, Lydon, B, MacAuley, K, McEwan, R, McGregor, P, McLaren, B, McLeod, L, Medforth, J, Miskimmin, R, Moffat, J, Pickup, M, Prentice, C, Rahman, M, Reda, E, Ross, C, Ryalls, A, Schmid, D, Shergill, N, Snaddon, A, Snell, H, Stevens, L, Waterman, A, Watts, V, Jayne, K, Keirnan, E, Newman, P, Ritchie, G, Rosenfeld, A, Beller, E, Gebski, V, Pillai, A, Anderson, C, Blakesmith, S, Chan, S-Y, Czyniewski, S, Dobbie, A, Doshi, S, Dupuy, A, Eckermann, S, Edwards, M, Fields, N, Flood, K, Ford, S, French, C, Gillies, S, Greig, C, Groshens, M, Gu, J, Guo, Y, Hague, W, Healy, S, Hones, L, Hossain, Z, Howlett, M, Lee, J, Li, L-P, Matthews, T, Micallef, J, Martin, A, Minns, I, Nguyen, A, Papuni, F, Patel, A, Pike, R, Pena, M, Pinto, K, Schipp, D, Schroeder, J, Sim, B, Sodhi, C, Sourjina, T, Sutton, C, Taylor, R, Vlagsma, P, Walder, S, Walker, R, Wong, W, Zhang, J, Zhong, B, Kokkonen, A, Narva, P, Niemi, E-L, Syrjanen, A-M, Lintott, C, Tirimacco, R, Kajosaari, M, Raman, L, Sundvall, J, Tukianen, M, Crimet, D, Sirugue, I, and Aubonnet, P
Subjects: Male, Cardiac & Cardiovascular Systems, Endocrinology, Diabetes and Metabolism, Atorvastatin, Coronary Disease, Fibrate, SECONDARY PREVENTION, ATORVASTATIN, law.invention, Placebos, Randomized controlled trial, Fenofibrate, law, Myocardial infarction, 1102 Cardiorespiratory Medicine and Haematology, Finland, Original Investigation, Hypolipidemic Agents, PLASMA, CHOLESTEROL, Middle Aged, INSULIN, CARDIOVASCULAR-DISEASE, Cardiovascular Diseases, Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, medicine.drug_class, Diabetes Complications, Endocrinology & Metabolism, Double-Blind Method, Internal medicine, Diabetes mellitus, Intervention (counseling), medicine, Humans, CORONARY-HEART-DISEASE, Obesity, Triglycerides, Aged, Apolipoproteins B, Bezafibrate, Science & Technology, business.industry, Cholesterol, HDL, Australia, Cholesterol, LDL, medicine.disease, BEZAFIBRATE, FIELD Study Investigators, MYOCARDIAL-INFARCTION, Diabetes Mellitus, Type 2, Cardiovascular System & Hematology, Cardiovascular System & Cardiology, business, HIGH-DENSITY-LIPOPROTEIN, New Zealand
Abstract: Objective The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics. Research design and methods FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred. Results About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of 30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement or treatment for hypertension (84%), high waist measurement (68%), and raised triglycerides (52%). After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%). Conclusion The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic syndrome. The main results of the study will be reported in late 2005.
Published: 2005

27. The need for a large-scale trial of fibrate therapy in diabetes: The rationale and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. [ISRCTN64783481]

Author: Barter, P, Best, J, Colman, P, d'Emden, M, Davis, T, Drury, P, Ehnholm, C, Glasziou, P, Hunt, D, Keech, A, Laakso, M, Scott, R, Simes, RJ, Sullivan, D, Taskinen, M-R, Whiting, M, Ansquer, J-C, Fraitag, B, Anderson, N, Hankey, G, Lehto, S, Mann, S, Romo, M, Li, LP, Akauola, H, Alford, F, Beinart, I, Bohra, S, Boyages, S, Connor, H, Darnell, D, Davoren, P, Lepre, F, De Looze, D, Duffield, A, Fassett, R, Flack, J, Fulcher, G, Grant, S, Hamwood, S, Harmelin, D, Jackson, R, Jeffries, W, Kamp, M, Kritharides, L, Mahar, L, McCann, V, McIntyre, D, Moses, R, Newnham, H, Nicholson, G, O'Brien, R, Park, K, Petrovsky, N, Phillips, P, Pinn, G, Simmons, D, Stanton, K, Stuckey, B, Sullivan, DR, Suranyi, M, Suthers, M, Tan, Y, Templer, M, Topliss, D, Waites, JH, Watts, G, Welborn, T, Wyndham, R, Haapamaki, H, Kesaniemi, A, Lahtela, J, Levanen, H, Saltevo, J, Sodervik, H, Taskinen, M, and Vanhala, M
Abstract: Background: Fibrates correct the typical lipid abnormalities of type 2 diabetes mellitus, yet no study, to date, has specifically set out to evaluate the role of fibrate therapy in preventing cardiovascular events in this setting. Methods: Subjects with type 2 diabetes, aged 50-75 years, were screened for eligibility to participate in a long-term trial of comicronized fenofibrate 200 mg daily compared with matching placebo to assess benefits of treatment on the occurrence of coronary and other vascular events. People with total cholesterol levels 3.0-6.5 mmol/L plus either a total-to-HDLc ratio >4.0 or triglyceride level >1.0 mmol /L with no clear indication for lipid-modifying therapy were eligible. Results: A total of 9795 people were randomized into the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. All received dietary advice, followed by a 6-week single-blind placebo run-in, then a 6-week active run-in period before randomization. Participants are being followed up every 6 months for outcome events and safety assessments. The study is designed to yield at least 500 coronary events (primary endpoint: first nonfatal myocardial infarction or coronary death) over 5 years, to have 80% power to identify as statistically significant at 2P = 0.05 a 22% reduction in such events, using intention-to-treat methods. Conclusions: Type 2 diabetes is the most common endocrine disorder worldwide, and its prevalence is increasing. The current evidence about use of fibrates in type 2 diabetes, from around 2000 people treated, will increase with FIELD to evidence from around 12000. FIELD will establish the role of fenofibrate treatment in reducing cardiovascular risk in people with type 2 diabetes. The main results are expected to be available in late 2005. © 2004 The FIELD Study Investigators; licensee BioMed Central Ltd.
Published: 2004

28. FRI-295 - Determination of a Normal value for HOMA-IR and cut-off Value for Non-Alcoholic Fatty Liver Disease

Author: Petäjä, E.M., Zhou, Y., Peltonen, M., Jouslahti, P., Männistö, S., Keinänen-Kiukaanniemi, S., Saltevo, J., and Yki-Järvinen, H.
Published: 2016
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29. Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: Baseline characteristics and short-term effects of fenofibrate [ISRCTN64783481]

Author: Keech, AC, Scott, R, Best, J, Forder, P, Taskinen, MR, Simes, J, Barter, P, Colman, P, d'Emden, M, Davis, T, Drury, P, Ehnholm, C, Glasziou, P, Hunt, D, Kesaniemi, YA, Laakso, M, Simes, RJ, Sullivan, D, Whiting, M, Ansquer, JC, Fraitag, B, Anderson, N, Hankey, G, Lehto, S, Mann, S, Romo, M, Li, LP, Hennekens, C, MacMahon, S, Pocock, S, Tonkin, A, Wilhelmsen, L, Akauola, H, Alford, F, Beinart, I, Bohra, S, Boyages, S, Connor, H, Darnell, D, Davoren, P, Lepre, F, De Looze, F, Duffield, A, Fassett, R, Flack, J, Fulcher, G, Grant, S, Hamwood, S, Harmelin, D, Jackson, R, Jeffries, W, Kamp, M, Kritharides, L, Mahar, L, McCann, V, McIntyre, D, Moses, R, Newnham, H, Nicholson, G, O'Brien, R, Park, K, Petrovsky, N, Phillips, P, Pinn, G, Simmons, D, Stanton, K, Stuckey, B, Sullivan, DR, Suranyi, M, Suthers, M, Tan, Y, Templer, M, Topliss, D, Waites, JH, Watts, G, Welborn, T, Wyndham, R, Haapamaki, H, Kesaniemi, A, Lahtela, J, Levanen, H, Saltevo, J, Sodervik, H, Taskinen, M, Vanhala, M, Baker, J, Burton, A, Dixon, P, Doran, J, Dunn, P, Graham, N, Hamer, A, Hedley, J, Lloyd, J, Manning, P, McPherson, I, Morris, S, Keech, AC, Scott, R, Best, J, Forder, P, Taskinen, MR, Simes, J, Barter, P, Colman, P, d'Emden, M, Davis, T, Drury, P, Ehnholm, C, Glasziou, P, Hunt, D, Kesaniemi, YA, Laakso, M, Simes, RJ, Sullivan, D, Whiting, M, Ansquer, JC, Fraitag, B, Anderson, N, Hankey, G, Lehto, S, Mann, S, Romo, M, Li, LP, Hennekens, C, MacMahon, S, Pocock, S, Tonkin, A, Wilhelmsen, L, Akauola, H, Alford, F, Beinart, I, Bohra, S, Boyages, S, Connor, H, Darnell, D, Davoren, P, Lepre, F, De Looze, F, Duffield, A, Fassett, R, Flack, J, Fulcher, G, Grant, S, Hamwood, S, Harmelin, D, Jackson, R, Jeffries, W, Kamp, M, Kritharides, L, Mahar, L, McCann, V, McIntyre, D, Moses, R, Newnham, H, Nicholson, G, O'Brien, R, Park, K, Petrovsky, N, Phillips, P, Pinn, G, Simmons, D, Stanton, K, Stuckey, B, Sullivan, DR, Suranyi, M, Suthers, M, Tan, Y, Templer, M, Topliss, D, Waites, JH, Watts, G, Welborn, T, Wyndham, R, Haapamaki, H, Kesaniemi, A, Lahtela, J, Levanen, H, Saltevo, J, Sodervik, H, Taskinen, M, Vanhala, M, Baker, J, Burton, A, Dixon, P, Doran, J, Dunn, P, Graham, N, Hamer, A, Hedley, J, Lloyd, J, Manning, P, McPherson, I, and Morris, S
Abstract: Objective: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics. Research design and methods: FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred. Results: About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of <5%, but nearly all had a 5-year stroke risk of <10%. Despite this, half of the cohort were obese (BMI >30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement (41%), high waist measurement (65%), and raised triglycerides (52%). After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%). Conclusion: The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic
Published: 2005

30. Serum Omega-6 Polyunsaturated Fatty Acids and the Metabolic Syndrome: A Longitudinal Population-based Cohort Study

Author: Vanhala, M., primary, Saltevo, J., additional, Soininen, P., additional, Kautiainen, H., additional, Kangas, A. J., additional, Ala-Korpela, M., additional, and Mantyselka, P., additional
Published: 2012
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31. Increase in physical activity and cardiometabolic risk profile change during lifestyle intervention in primary healthcare: 1-year follow-up study among individuals at high risk for type 2 diabetes

Author: Kujala, U. M., primary, Jokelainen, J., additional, Oksa, H., additional, Saaristo, T., additional, Rautio, N., additional, Moilanen, L., additional, Korpi-Hyovalti, E., additional, Saltevo, J., additional, Vanhala, M., additional, Niskanen, L., additional, Peltonen, M., additional, Tuomilehto, J., additional, Uusitupa, M., additional, and Keinanen-Kiukaannemi, S., additional
Published: 2011
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32. Serum calcium level is associated with metabolic syndrome in the general population: FIN-D2D study

Author: Saltevo, J, primary, Niskanen, Leo, additional, Kautiainen, Hannu, additional, Teittinen, Jorma, additional, Oksa, Heikki, additional, Korpi-Hyövälti, Eeva, additional, Sundvall, Jouko, additional, Männistö, Satu, additional, Peltonen, Markku, additional, Mäntyselkä, Pekka, additional, and Vanhala, Mauno, additional
Published: 2011
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33. Sleep‐disordered breathing is related to an increased risk for type 2 diabetes in middle‐aged men, but not in women – the FIN‐D2D survey

Author: Tuomilehto, H., primary, Peltonen, M., additional, Partinen, M., additional, Seppä, J., additional, Saaristo, T., additional, Korpi‐Hyövälti, E., additional, Oksa, H., additional, Saltevo, J., additional, Puolijoki, H., additional, Vanhala, M., additional, and Tuomilehto, J., additional
Published: 2007
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34. Die Ausbreitung stoppen - Das Finnische Diabetesprogramm zur Prävention des Typ-2-Diabetes

Author: Saaristo, Timo, primary, Peltonen, M., additional, Keinänen-Kiukaanniemi, S., additional, Vanhala, M., additional, Saltevo, J., additional, Oksa, H., additional, Korpi-Hyövälti, E., additional, and Tuomilehto, J., additional
Published: 2007
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35. Treatment of hypercholesterolemia and combined hyperlipidemia with simvastatin and gemfibrozil in patients with NIDDM. A multicenter comparison study.

Author: Tikkanen MJ, Laakso M, Ilmonen M, Helve E, Kaarsalo E, Kilkki E, Saltevo J, Scandinavian Simvastation Survival Study Group, Tikkanen, M J, Laakso, M, Ilmonen, M, Helve, E, Kaarsalo, E, Kilkki, E, and Saltevo, J
Published: 1998
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36. Plasma endothelin in postmenopausal women with type 2 diabetes mellitus and metabolic syndrome: a comparison of oral combined and transdermal oestrogen-only replacement therapy

Author: Saltevo, J., primary, Puolakka, J., additional, and Ylikorkala, O., additional
Published: 2000
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37. Complications of nephropathia epidemica: three cases

Author: FORSLUND, T., primary, SALTEVO, J., additional, ANTTINEN, J., additional, AUVINEN, S., additional, BRUMMER-KORVENKONTIO, M., additional, KORHONEN, A., additional, and POUTIAINEN, M., additional
Published: 1992
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38. Cardiometabolic profile of people screened for high risk of type 2 diabetes in a national diabetes prevention programme (FIN-D2D)

Author: Saaristo T, Moilanen L, Jokelainen J, Korpi-Hyövälti E, Vanhala M, Saltevo J, Niskanen L, Peltonen M, Oksa H, Cederberg H, Tuomilehto J, Uusitupa M, and Keinänen-Kiukaanniemi S
Published: 2010
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39. Lifestyle intervention for prevention of type 2 diabetes in primary health care: one-year follow-up of the Finnish National Diabetes Prevention Program (FIN-D2D).

Author: Saaristo T, Moilanen L, Korpi-Hyövälti E, Vanhala M, Saltevo J, Niskanen L, Jokelainen J, Peltonen M, Oksa H, Tuomilehto J, Uusitupa M, Keinänen-Kiukaanniemi S, Saaristo, Timo, Moilanen, Leena, Korpi-Hyövälti, Eeva, Vanhala, Mauno, Saltevo, Juha, Niskanen, Leo, Jokelainen, Jari, and Peltonen, Markku
Abstract: Objective: To investigate 1-year outcomes of a national diabetes prevention program in Finland.Research Design and Methods: Altogether 10,149 individuals at high risk for diabetes were identified with the Finnish Diabetes Risk Score (FINDRISC; scoring ≥15 points), by a history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), cardiovascular disease, or gestational diabetes mellitus in 400 primary health care centers. One-year follow-up data were available for 2,798 participants who were nondiabetic at baseline (919 men and 1,879 women, aged 56.0 ± 9.9 and 54.0 ± 10.7 years [mean ± SD] with BMI 30.9 ± 4.6 and 31.6 ± 5.4 kg/m(2)).Results: The incidence of diabetes was 2.0 and 1.2% in men and women with normal glucose tolerance at baseline, 13.5 and 7.4% in those with IFG, and 16.1 and 11.3% in those with IGT, respectively. Altogether 17.5% of the subjects lost ≥ 5% weight with no sex difference. The relative risk of diabetes was 0.31 (95% CI 0.16-0.59) in the group who lost ≥ 5% weight, 0.72 (0.46-1.13) in the group who lost 2.5-4.9% weight, and 1.10 (0.77-1.58) in the group who gained ≥ 2.5% compared with the group who maintained weight.Conclusions: The FIN-D2D was the first national effort to implement the prevention of diabetes in a primary health care setting. Methods for recruiting high-risk subjects were simple and easy to use. Moderate weight loss in this very high-risk group was especially effective in reducing risk of diabetes among those participating in the program. [ABSTRACT FROM AUTHOR]
Published: 2010
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40. Sleep-disordered breathing is related to an increased risk for type 2 diabetes in middle-aged men, but not in women – the FIN-D2D survey.

Author: Tuomilehto, H., Peltonen, M., Partinen, M., Seppä, J., Saaristo, T., Korpi-Hyövälti, E., Oksa, H., Saltevo, J., Puolijoki, H., Vanhala, M., and Tuomilehto, J.
Subjects: SLEEP apnea syndromes, MIDDLE-aged men, TYPE 2 diabetes, METABOLIC disorders, OBESITY
Abstract: Aim: To determine the association between sleep-disordered breathing (SDB) and obesity, diabetes and glucose intolerance among middle-aged men and women in Finland. Methods: A multicentre, population-based, cross-sectional survey in Finland. A total of 1396 men and 1500 women aged 45–74 years participated in the survey between 2004 and 2005. The study subjects underwent a health examination including an oral glucose tolerance test and filled a questionnaire describing their sleep habits. Results: Middle-aged men with SDB had an increased prevalence of diabetes and abnormal glucose tolerance. These associations were not found among middle-aged women. After adjustments for age, body mass index, smoking and central nervous system–affecting medication, SDB was independently associated with diabetes and glucose intolerance in men, but not in women. Conclusion: Middle-aged men with SDB have an independent risk of type 2 diabetes. However, both diabetes and SDB exhibit a strong association with obesity and especially with central obesity, reflecting increased visceral fat. In clinical practice especially male patients with diabetes should always be asked about habitual snoring and about possible sleep apnoea. [ABSTRACT FROM AUTHOR]
Published: 2008
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41. A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes

Author: van Zuydam, Natalie R, Ahlqvist, Emma, Sandholm, Niina, Deshmukh, Harshal, Rayner, N William, Abdalla, Moustafa, Ladenvall, Claes, Ziemek, Daniel, Fauman, Eric, Robertson, Neil R, Mckeigue, Paul M, Valo, Erkka, Forsblom, Carol, Harjutsalo, Valma, Perna, Annalisa, Rurali, Erica, Marcovecchio, M Loredana, Igo, Robert P, Salem, Rany M, Perico, Norberto, Lajer, Maria, Käräjämäki, Annemari, Imamura, Minako, Kubo, Michiaki, Takahashi, Atsushi, Sim, Xueling, Liu, Jianjun, van Dam, Rob M, Jiang, Guozhi, Tam, Claudia H T, Luk, Andrea O Y, Lee, Heung Man, Lim, Cadmon K P, Szeto, Cheuk Chun, Wing Yee, So, Chan, Juliana C N, Ang, Su Fen, Dorajoo, Rajkumar, Wang, Ling, Clara, Tan Si Hua, Mcknight, Amy-Jayne, Duffy, Seamus, Pezzolesi, Marcus G, Marre, Michel, Gyorgy, Beata, Hadjadj, Samy, Hiraki, Koivula, S, Uggeldahl, T, Forslund, T, Halonen, A, Koistinen, A, Koskiaho, P, Laukkanen, M, Saltevo, J, Tiihonen, M, Forsen, M, Granlund, H, Jonsson, Ac, Nyroos, B, Kinnunen, P, Orvola, A, Salonen, T, Vähänen, A, Paldanius, Kr, Riihelä, M, Ryysy, L, Laukkanen, Kh, Nyländen, P, Sademies, A, Anderson, S, Asplund, B, Byskata, U, Liedes, P, Kuusela, M, Virkkala, T, Nikkola, A, Ritola, E, Niska, Tm, Saarinen, H, Oukko-Ruponen, Se, Virtanen, T, Lyytinen, Va, Kari, Ph, Simonen, T, Kaprio, Sa, Kärkkäinen, J, Rantaeskola, B, Kääriäinen, Tp, Haaga, J, Pietiläinen, Al, Klemetti, S, Nyandoto, T, Rontu, E, Satuli-Autere, S, Toivonen, Kr, Lansimaki, Hv, Ahonen, R, Ivaska-Suomela, M, Jauhiainen, A, Laine, Mm, Pellonpää, T, Puranen, R, Airas, Ma, Laakso, J, Rautavaara, K, Erola, Rm, Jatkola, E, Lönnblad, Tr, Malm, A, Mäkelä, J, Rautamo, E, Hentunen, P, Lagerstam, J, Feodoroff, M, Gordin, D, Heikkilä, O, Hietala, K, Fagerudd, J, Korolainen, M, Kyllönen, L, Kytö, J, Lindh, S, Pettersson-Fernholm, K, Rosengård-Bärlund, M, Sandelin, A, Thorn, L, Tuomikangas, J, Vesisenaho, T, Wadén, J, Sipilä, V, Kalliomäki, Ft, Koskelainen, J, Nikkanen, R, Savolainen, N, Sulonen, H, Valtonen, E, Norvio, L, Hämäläinen, A, Toivanen, E, Parta, Ja, Pirttiniemi, I, Aranko, S, Ervasti, S, Kauppinen-Mäkelin, R, Kuusisto, A, Leppälä, T, Nikkilä, K, Pekkonen, L, Jokelainen, Ks, Kananen, K, Karjalainen, M, Kemppainen, P, Mankinen, Am, Reponen, A, Sankari, M, Suominen, P, Lappalainen, A, Liimatainen, M, Santaholma, J, Aimolahti, A, Huovinen, E, Ilkka, V, Lehtimäki, M, Pälikkö-Kontinen, E, Vanhanen, A, Koskinen, E, Siitonen, T, Huttunen, E, Ikäheimo, R, Karhapää, P, Kekäläinen, P, Laakso, M, Lakka, T, Lampainen, E, Moilanen, L, Tanskanen, S, Niskanen, L, Tuovinen, U, Vauhkonen, I, Voutilainen, E, Rcw, Ma, Chan, Jcn, Huang, Y, Lan, Hy, Lok, S, Tomlinson, B, Tsui, Skw, Yu, W, Yip, Kyl, Chan, Tf, Fan, X, So, Wy, Szeto, Cc, Tang, N, Luk, Ao, Tian, X, Jiang, G, Tam, Cht, Lee, Hm, Lim, Ckp, Chan, Kkh, Xie, F, Acw, Ng, Cheung, Gpy, Yeung, Mw, Mai, S, Zhang, S, Yu, P, Weng, M, Maxwell, Ap, Mcknight, Aj, Savage, Da, Walker, J, Thomas, S, Viberti, Gc, Boulton, Ajm, Marshall, S, Demaine, Ag, Millward, Ba, Bain, Sc, Sandholm, N, Forsblom, C, Harjutsalo, V, Mäkinen, Vp, Ahola, Aj, Dahlström, E, Lehto, M, Lithovius, R, Panduru, Nm, Parkkonen, M, Saraheimo, M, Söderlund, J, Soro-Paavonen, A, Syreeni, A, Thorn, Lm, Tolonen, N, Groop, Ph, Mckay, Gj, Salem, Rm, Isakova, T, Palmer, C, Guiducci, C, Taylor, A, Mirel, Db, Williams, Ww, Hirschhorn, Jn, Florez, Jc, Brennan, Ep, Sadlier, Dm, Martin, F, Godson, C, Mayer, L, Gubitosi-Klug, R, Bourne, P, Schutta, M, Lackaye, Me, Gregory, Ns, Kruger, D, Jones, Jk, Bhan, A, Golden, E, Aiello, L, Larkin, M, Nathan, D, Ziegler, G, Caulder, S, Pittman, C, Luttrell, L, Lopes-Virella, M, Johnson, M, Gunyou, K, Bergenstal, R, Vittetoe, B, Sivitz, W, Flaherty, N, Bantle, J, Hitt, S, Goldstein, D, Hainsworth, D, Cimino, L, Orchard, T, Wigley, C, Dagogo-Jack, S, Strowig, S, Raskin, P, Barnie, A, Zinman, B, Fahlstrom, R, Palmer, J, Harth, J, Driscoll, M, Mcdonald, C, Lipps Hagan, J, May, M, Levandoski, L, White, N, Gatcomb, P, Tamborlane, W, Adelman, D, Colson, S, Molitch, M, Lorenzi, G, Mudaliar, S, Johnsonbaugh, S, Miller, R, Canady, J, Schade, D, Bernal, Ml, Malone, J, Morrison, A, Martin, C, Herman, W, Pop-Busui, R, Cowie, C, Leschek, E, Cleary, P, Lachin, J, Braffett, B, Steffes, M, Arends, V, Blodi, B, Danis, R, Lawrence, D, Wabers, H, Soliman, E, Zhang, Zm, Campbell, C, Hensley, S, Keasler, L, Mark, M, Albertini, M, Boustany, C, Ehlgen, A, Gerl, M, Huber, J, Schölch, C, Zimdahl-Gelling, H, Groop, L, Agardh, E, Ahlqvist, E, Ajanki, T, Al Maghrabi, N, Almgren, P, Apelqvist, J, Bengtsson, E, Berglund, L, Björckbacka, H, Blom-Nilsson, U, Borell, M, Burström, A, Cilio, C, Cinthio, M, Dreja, K, Dunér, P, Engelbertsen, D, Fadista, J, Gomez, M, Goncalves, I, Hedblad, B, Hultgårdh, A, Johansson, Me, Kennbäck, C, Kravic, J, Ladenvall, C, Lernmark, Å, Lindholm, E, Ling, C, Luthman, H, Melander, O, Neptin, M, Nilsson, J, Nilsson, P, Nilsson, T, Nordin, G, Orho-Melander, M, Ottoson-Laakso, E, Persson, A, Persson, M, Persson, Må, Postma, J, Pranter, E, Rattik, S, Sterner, G, Tindberg, L, Wigren, M, Zetterqvist, A, Åkerlund, M, Ostling, G, Kanninen, T, Ahonen-Bishopp, A, Eliasson, A, Herrala, T, Tikka-Kleemola, P, Hamsten, A, Betsholtz, C, Björkholm, A, Foroogh, F, Genové, G, Gertow, K, Gigante, B, He, B, Leander, K, Mcleod, O, Nastase-Mannila, M, Patrakka, J, Silveira, A, Strawbridge, R, Tryggvason, K, Vikström, M, Ohrvik, J, Österholm, Am, Thorand, B, Gieger, C, Grallert, H, Ludwig, T, Nitz, B, Schneider, A, Wang-Sattler, R, Zierer, A, Remuzzi, G, Benigni, A, Donadelli, R, Lesti, Md, Noris, M, Perico, N, Perna, A, Piras, R, Ruggenenti, P, Rurali, E, Dunger, D, Chassin, L, Dalton, N, Deanfield, J, Horsford, J, Rice, C, Rudd, J, Walker, N, Whitehead, K, Wong, M, Colhoun, H, Adams, F, Akbar, T, Belch, J, Deshmukh, H, Dove, F, Ellingford, A, Farran, B, Ferguson, M, Henderson, G, Houston, G, Khan, F, Leese, G, Liu, Y, Livingstone, S, Looker, H, Mccann, M, Mcgurnaghan, S, Morris, A, Newton, D, Pearson, E, Reekie, G, Smith, N, Shore, A, Aizawa, K, Ball, C, Bellenger, N, Casanova, F, Frayling, T, Gates, P, Gooding, K, Hattersley, A, Ling, R, Mawson, D, Shandas, R, Strain, D, Thorn, C, Smith, U, Hammarstedt, A, Häring, H, Pedersen, O, Sesti, G, Fagerholm, E, Toppila, I, Valo, E, Salomaa, V, Havulinna, A, Kristiansson, K, Okamo, P, Peltola, T, Perola, M, Pietilä, A, Ripatti, S, Taimi, M, Ylä-Herttuala, S, Babu, M, Dijkstra, M, Gurzeler, E, Huusko, J, Kholová, I, Merentie, M, Poikolainen, M, Mccarthy, M, Groves, C, Juliusdottir, T, Karpe, F, Lagou, V, Rayner, W, Robertson, N, van Zuydam, N, Cobelli, C, Di Camillo, B, Finotello, F, Sambo, F, Toffolo, G, Trifoglio, E, Bellazzi, R, Barbarini, N, Bucalo, M, Larizza, C, Magni, P, Malovini, A, Marini, S, Mulas, F, Quaglini, S, Sacchi, L, Vitali, F, Ferrannini, E, Boldrini, B, Kozakova, M, Mari, A, Morizzo, C, Mota, L, Natali, A, Palombo, C, Venturi, E, Walker, M, Patrono, C, Pagliaccia, F, Rocca, B, Nuutila, P, Haukkala, J, Knuuti, J, Roivainen, A, Saraste, A, Mckeague, P, Colombo, M, Steckel-Hamann, B, Bokvist, K, Shankar, S, Thomas, M, Gan, Lm, Heinonen, S, Jönsson-Rylander, Ac, Momo, R, Schnecke, V, Unwin, R, Walentinsson, A, Whatling, C, Nogoceke, E, Pacheco, Gd, Formentini, I, Schindler, T, Tortoli, P, Bassi, L, Boni, E, Dallai, A, Guidi, F, Lenge, M, Matera, R, Ramalli, A, Ricci, S, Viti, J, Jablonka, B, Crowther, D, Gassenhuber, J, Hess, S, Hubschle, T, Juretschke, Hp, Rutten, H, Sadowski, T, Wohlfart, P, Brosnan, J, Clerin, V, Fauman, E, Hyde, C, Malarstig, A, Pullen, N, Tilley, M, Tuthill, T, Vangjeli, C, Linda T, Ziemek D., Ahluwalia, Tarunveer S, Almgren, Peter, Schulz, Christina-Alexandra, Orho-Melander, Marju, Linneberg, Allan, Christensen, Cramer, Witte, Daniel R, Grarup, Niels, Brandslund, Ivan, Melander, Olle, Paterson, Andrew D, Tregouet, David, Maxwell, Alexander P, Lim, Su Chi, Ronald C W, Ma, Tai, E Shyong, Maeda, Shiro, Lyssenko, Valeriya, Tuomi, Tiinamaija, Krolewski, Andrzej S, Rich, Stephen S, Hirschhorn, Joel N, Florez, Jose C, Dunger, David, Pedersen, Oluf, Hansen, Torben, Rossing, Peter, Remuzzi, Giuseppe, Brosnan, Mary Julia, Palmer, Colin N A, Groop, Per-Henrik, Colhoun, Helen M, Groop, Leif C, Mccarthy, Mark, I, Palombo, Carlo, Clinicum, Diabetes and Obesity Research Program, Research Programs Unit, Nefrologian yksikkö, Department of Medicine, Institute for Molecular Medicine Finland, Tiinamaija Tuomi Research Group, Endokrinologian yksikkö, Per Henrik Groop / Principal Investigator, Leif Groop Research Group, HUS Abdominal Center, HUS Internal Medicine and Rehabilitation, and Lee Kong Chian School of Medicine (LKCMedicine)
Subjects: 0301 basic medicine, Male, endocrine system diseases, Endocrinology, Diabetes and Metabolism, LOCI, Genome-wide association study, Type 2 diabetes, Bioinformatics, Kidney Failure, 0302 clinical medicine, Genome-wide analysis, 80 and over, Diabetic Nephropathies, Renal Insufficiency, Chronic, Genome-wide analysis, Type 2 Diabetes, Aged, 80 and over, RISK, INSULIN-RESISTANCE, diabetes, Diabetes, STAGE RENAL-DISEASE, Single Nucleotide, Middle Aged, Type 2 Diabetes, SUSCEPTIBILITY GENES, Adult, Aged, Case-Control Studies, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney Failure, Chronic, Polymorphism, Single Nucleotide, Renal Insufficiency, Chronic, OBESITY, BIOLOGICAL PATHWAYS, nephropathy, Medical genetics, Type 2, kidney, medicine.medical_specialty, Diabetic Nephropathies/epidemiology, Settore BIO/14 - FARMACOLOGIA, Renal Insufficiency, Chronic/complications, NEPHROPATHY, SNP, 030209 endocrinology & metabolism, Nephropathy, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Diabetes mellitus, Journal Article, Diabetes Mellitus, Internal Medicine, medicine, Medicine [Science], Polymorphism, Diabetic Kidney Disease, METAANALYSIS, Genetic heterogeneity, business.industry, Diabetes Mellitus, Type 2/complications, association, Case-control study, nutritional and metabolic diseases, Kidney Failure, Chronic/complications, FAT DISTRIBUTION, medicine.disease, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, Microalbuminuria, genetic, business
Abstract: Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD. ASTAR (Agency for Sci., Tech. and Research, S’pore) NMRC (Natl Medical Research Council, S’pore)
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42. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Author: Wheeler, E, Leong, A, Liu, C-T, Hivert, M-F, Strawbridge, RJ, Podmore, C, Li, M, Yao, J, Sim, X, Hong, J, Chu, AY, Zhang, W, Wang, X, Chen, P, Maruthur, NM, Porneala, BC, Sharp, SJ, Jia, Y, Kabagambe, EK, Chang, L-C, Chen, W-M, Elks, CE, Evans, DS, Fan, Q, Giulianini, F, Go, MJ, Hottenga, J-J, Hu, Y, Jackson, AU, Kanoni, S, Kim, YJ, Kleber, ME, Ladenvall, C, Lecoeur, C, Lim, S-H, Lu, Y, Mahajan, A, Marzi, C, Nalls, MA, Navarro, P, Nolte, IM, Rose, LM, Rybin, DV, Sanna, S, Shi, Y, Stram, DO, Takeuchi, F, Tan, SP, Van Der Most, PJ, Van Vliet-Ostaptchouk, JV, Wong, A, Yengo, L, Zhao, W, Goel, A, Martinez Larrad, MT, Radke, D, Salo, P, Tanaka, T, Van Iperen, EPA, Abecasis, G, Afaq, S, Alizadeh, BZ, Bertoni, AG, Bonnefond, A, Böttcher, Y, Bottinger, EP, Campbell, H, Carlson, OD, Chen, C-H, Cho, YS, Garvey, WT, Gieger, C, Goodarzi, MO, Grallert, H, Hamsten, A, Hartman, CA, Herder, C, Hsiung, CA, Huang, J, Igase, M, Isono, M, Katsuya, T, Khor, C-C, Kiess, W, Kohara, K, Kovacs, P, Lee, J, Lee, W-J, Lehne, B, Li, H, Liu, J, Lobbens, S, Luan, J, Lyssenko, V, Meitinger, T, Miki, T, Miljkovic, I, Moon, S, Mulas, A, Müller, G, Müller-Nurasyid, M, Nagaraja, R, Nauck, M, Pankow, JS, Polasek, O, Prokopenko, I, Ramos, PS, Rasmussen-Torvik, L, Rathmann, W, Rich, SS, Robertson, NR, Roden, M, Roussel, R, Rudan, I, Scott, RA, Scott, WR, Sennblad, B, Siscovick, DS, Strauch, K, Sun, L, Swertz, M, Tajuddin, SM, Taylor, KD, Teo, Y-Y, Tham, YC, Tönjes, A, Wareham, NJ, Willemsen, G, Wilsgaard, T, Hingorani, AD, EPIC-CVD Consortium, EPIC-InterAct Consortium, Lifelines Cohort Study, Egan, J, Ferrucci, L, Hovingh, GK, Jula, A, Kivimaki, M, Kumari, M, Njølstad, I, Palmer, CNA, Serrano Ríos, M, Stumvoll, M, Watkins, H, Aung, T, Blüher, M, Boehnke, M, Boomsma, DI, Bornstein, Chambers, JC, Chasman, DI, Chen, Y-DI, Chen, Y-T, Cheng, C-Y, Cucca, F, De Geus, EJC, Deloukas, P, Evans, MK, Fornage, M, Friedlander, Y, Froguel, P, Groop, L, Gross, MD, Harris, TB, Hayward, C, Heng, C-K, Ingelsson, E, Kato, N, Kim, B-J, Koh, W-P, Kooner, JS, Körner, A, Kuh, D, Kuusisto, J, Laakso, M, Lin, X, Liu, Y, Loos, RJF, Magnusson, PKE, März, W, McCarthy, MI, Oldehinkel, AJ, Ong, KK, Pedersen, NL, Pereira, MA, Peters, A, Ridker, PM, Sabanayagam, C, Sale, M, Saleheen, D, Saltevo, J, Schwarz, PE, Sheu, WHH, Snieder, H, Spector, TD, Tabara, Y, Tuomilehto, J, Van Dam, RM, Wilson, JG, Wilson, JF, Wolffenbuttel, BHR, Wong, TY, Wu, J-Y, Yuan, J-M, Zonderman, AB, Soranzo, N, Guo, X, Roberts, DJ, Florez, JC, Sladek, R, Dupuis, J, Morris, AP, Tai, E-S, Selvin, E, Rotter, JI, Langenberg, C, Barroso, I, and Meigs, JB
Subjects: Hemoglobin A, Glycosylated, endocrine system diseases, Diabetes Mellitus, Type 2, phenotype, genetic variation, nutritional and metabolic diseases, humans, 3. Good health, Genome-Wide Association Study, risk
Abstract: BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. METHODS & FINDINGS: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. CONCLUSIONS: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.

43. Sleep duration is associated with an increased risk for the prevalence of type 2 diabetes in middle-aged women - The FIN-D2D survey.

Author: Tuomilehto H, Peltonen M, Partinen M, Seppä J, Saaristo T, Korpi-Hyövälti E, Oksa H, Puolijoki H, Saltevo J, Vanhala M, and Tuomilehto J
Published: 2008
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44. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial

Author: Paresh Dandona, Chantal Mathieu, Moshe Phillip, Lars Hansen, Steven C Griffen, Diethelm Tschöpe, Fredrik Thorén, John Xu, Anna Maria Langkilde, Joseph Proietto, Stephen Stranks, Roger Chen, David O'Neal, Alexia Pape, Mark Forbes, Claire Morbey, Anton Luger, Ursula Hanusch, Christoph Schnack, Evelyn Fliesser-Goerzer, Bertram Hoelzl, Christoph Ebenbichler, Rudolf Prager, Luc Van Gaal, Chris Vercammen, Andre Scheen, Francis Duyck, Frank Nobels, Johannes Ruige, Naresh Aggarwal, Vincent Woo, Bruno St-Pierre, Richard Dumas, Irene Hramiak, Thomas Elliott, Troels Krarup Hansen, Jan Erik Henriksen, Jeppe Gram, Aina Lihn, Jens Bruun, Juha Saltevo, Jyrki Taurio, Jorma Strand, Timo Valle, Sakari Nieminen, Kirsi Pietilainen, Bruno Guerci, Samy Hadjadj, Bertrand Cariou, Bruno Verges, Sophie Borot, Alfred Penfornis, Thomas Schaum, Diethelm Tschoepe, Cornelia Marck, Thomas Horacek, Ludger Rose, Gerhard Klausmann, Joerg Luedemann, Steffi Appelt, Ulrich Aigner, Rolf Goebel, Thomas Behnke, Anette-Gabriele Ziegler, Eva Peterfai, Zsuzsanna Kerenyi, Tamas Oroszlan, Gyula G. Kiss, Laszlo Konyves, Gyorgyi Piros, Ofri Mosenzon, Naim Shehadeh, Faiad Adawi, Julio Wainstein, Francesco Dotta, Piermarco Piatti, Stefano Genovese, Agostino Consoli, Paolo Di Bartolo, Edoardo Mannucci, Carla Giordano, Annunziata Lapolla, Carlos Aguilar, Alberto Esteban, Bazzoni Ruiz, Guillermo Mondragon Ramirez, Emilia Pelayo Orozco, Carlos Alejandro, Stobschinski de Alba, Carlos Medina Pech, Jose Garza Ruiz, Leobardo Sauque Reyna, Guillermo Llamas Esperon, Luis Alejandro Nevarez Ruiz, Maricela Vidrio Velazquez, Fernando Flores Lozano, Jose Gerardo Gonzalez Gonzalez, Pedro Alberto Garcia-Hernandez, Roberto Araujo-Silva, Efrain Villeda - Espinosa, Cristina Mistodie, Daniela Popescu, Ciprian Constantin, Alina Nicolau, Bogdan Popa, Romulus Timar, Cristian Serafinceanu, Ella Pintilei, Alfonso Soto, Margarita Gimenez, Juan Francisco Merino-Torres, Cristobal Morales, Pedro Mezquita, Johan Jendle, Bengt-Olov Tengmark, Jan Eriksson, Magnus Londahl, Bjorn Eliasson, Anthony Gunstone, Simon Heller, Ken Darzy, Peter Mansell, Melanie Davies, Rory Reed, Duncan Browne, Hamish Courtney, Wayne Turner, Mark Blagden, Rory McCrimmon, Richard Bergenstal, Wendy Lane, Kathryn Lucas, Alexander White, Shichun Bao, Judith White, Curtis Jantzi, Neda Rasouli, William Ervin, Lorena Lewy-Alterbaum, Yehuda Handelsman, Bresta Miranda-Palma, Alan Cleland, Raymond Fink, Helena Rodbard, Samer Nakhle, Craig Greenberg, Alan Schorr, Harold Bays, Debra Simmons, Eric Klein, Laurie Kane, Norman Fishman, Eli Ipp, Satish Garg, Anuj Bhargava, Michelle Zaniewski Singh, Julio Rosenstock, James Thrasher, Mark Warren, Laura Young, Vanita Aroda, Jeremy Pettus, David Liljenquist, Robert Busch, Jonathan Wise, David Kayne, William Biggs, Dandona P., Mathieu C., Phillip M., Hansen L., Griffen S.C., Tschope D., Thoren F., Xu J., Langkilde A.M., Proietto J., Stranks S., Chen R., O'Neal D., Pape A., Forbes M., Morbey C., Luger A., Hanusch U., Schnack C., Fliesser-Goerzer E., Hoelzl B., Ebenbichler C., Prager R., Van Gaal L., Vercammen C., Scheen A., Duyck F., Nobels F., Ruige J., Aggarwal N., Woo V., St-Pierre B., Dumas R., Hramiak I., Elliott T., Krarup Hansen T., Henriksen J.E., Gram J., Lihn A., Bruun J., Saltevo J., Taurio J., Strand J., Valle T., Nieminen S., Pietilainen K., Guerci B., Hadjadj S., Cariou B., Verges B., Borot S., Penfornis A., Schaum T., Tschoepe D., Marck C., Horacek T., Rose L., Klausmann G., Luedemann J., Appelt S., Aigner U., Goebel R., Behnke T., Ziegler A.-G., Peterfai E., Kerenyi Z., Oroszlan T., Kiss G.G., Konyves L., Piros G., Mosenzon O., Shehadeh N., Adawi F., Wainstein J., Dotta F., Piatti P., Genovese S., Consoli A., Di Bartolo P., Mannucci E., Giordano C., Lapolla A., Aguilar C., Esteban A., Ruiz B., Ramirez G.M., Pelayo Orozco E., Alejandro C., de Alba S., Medina Pech C., Garza Ruiz J., Sauque Reyna L., Llamas Esperon G., Nevarez Ruiz L.A., Vidrio Velazquez M., Flores Lozano F., Gonzalez Gonzalez J.G., Garcia-Hernandez P.A., Araujo-Silva R., Villeda - Espinosa E., Mistodie C., Popescu D., Constantin C., Nicolau A., Popa B., Timar R., Serafinceanu C., Pintilei E., Soto A., Gimenez M., Merino J., Morales C., Mezquita P., Jendle J., Tengmark B.-O., Eriksson J., Londahl M., Eliasson B., Gunstone A., Heller S., Darzy K., Mansell P., Davies M., Reed R., Browne D., Courtney H., Turner W., Blagden M., McCrimmon R., Bergenstal R., Lane W., Lucas K., White A., Bao S., White J., Jantzi C., Rasouli N., Ervin W., Lewy-Alterbaum L., Handelsman Y., Miranda-Palma B., Cleland A., Fink R., Rodbard H., Nakhle S., Greenberg C., Schorr A., Bays H., Simmons D., Klein E., Kane L., Fishman N., Ipp E., Garg S., Bhargava A., Singh M.Z., Rosenstock J., Thrasher J., Warren M., Young L., Aroda V., Pettus J., Liljenquist D., Busch R., Wise J., Kayne D., and Biggs W.
Subjects: Male, Glycated Hemoglobin A, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Settore MED/13 - Endocrinologia, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, diabetes, dapaglifozin, Glucosides, Randomized controlled trial, law, Insulin, 03.02. Klinikai orvostan, Dapagliflozin, Middle Aged, Diabetes and Metabolism, Treatment Outcome, Combination, Drug Therapy, Combination, Female, Type 1, Adult, medicine.medical_specialty, Diabetic ketoacidosis, 030209 endocrinology & metabolism, Placebo, 03 medical and health sciences, Drug Therapy, Diabetes management, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Benzhydryl Compounds, Body Weight, Diabetes Mellitus, Type 1, Hypoglycemia, Glycated Hemoglobin, Type 1 diabetes, business.industry, medicine.disease, Surgery, chemistry, business
Abstract: Background Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. Methods DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18–75 years and had inadequately controlled type 1 diabetes (HbA1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment. After an 8 week lead-in period to optimise diabetes management, patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo. Randomisation was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c. The primary efficacy outcome was the change from baseline in HbA1c after 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug. An additional 55 patients who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups were included in the safety analysis set. This study was registered with ClinicalTrials.gov, number NCT02268214; data collection for the present analysis was completed on Jan 4, 2017, and a 28 week extension phase is ongoing. Findings Between Nov 11, 2014, and April 16, 2016, 833 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]; 778 of these patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients). Mean baseline HbA1c was 8·53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]). At week 24, both doses of dapagliflozin significantly reduced HbA1c compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0·42% [95% CI −0·56 to −0·28; p
Published: 2017
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45. Is living alone associated with mortality among older primary care patients with or without diabetes?

Author: Aro AK, Karjalainen M, Tiihonen M, Kautiainen H, Saltevo J, Haanpää M, and Mäntyselkä P
Subjects: Humans, Female, Male, Aged, Finland epidemiology, Aged, 80 and over, Proportional Hazards Models, Case-Control Studies, Kaplan-Meier Estimate, Mortality trends, Registries, Diabetes Mellitus mortality, Diabetes Mellitus epidemiology, Primary Health Care statistics & numerical data
Abstract: Aims: The aim of this study was to evaluate the association between living alone and mortality among older patients with and without diabetes., Methods: Electronic patient records were used to identify patients at least 65 years of age with a diagnosis of diabetes and two age- and sex-matched controls without diabetes for each patient with diabetes in 2015. The study population in this analysis consisted of 429 patients with diabetes and 650 controls who returned a questionnaire that contained questions about their diseases, symptoms, and functions. The mortality (2015-2019) data were based on the national registry of Statistics Finland. Cumulative mortality was estimated with Kaplan-Meier's method and compared with the log-rank test. Cox proportional hazards regression was used to estimate the adjusted hazard ratios (HR) and their 95% confidence intervals (CI)., Results: The median follow-up time was 4.3 years. 208 of the controls (32%) and 156 (36%) of the patients with diabetes lived alone. Of the controls, 8.1% (95% CI 5.9-11.1) of those not living alone and 20.2% (95% CI 15.3-26.3) living alone died. The corresponding numbers for patients with diabetes were 15.1% (95% CI 11.3-19.8) and 28.8% (95% CI 22.4-36.7). Among all patients, living alone was associated with increased mortality (HR = 1.84; 95% Cl 1.30-2.61), whereas the diagnosis of diabetes was not (HR = 1.31; 95% Cl 0.94-1.81)., Conclusions: The results of this study show that living alone had a significant impact on the mortality of older patients, regardless of whether they had diabetes or not. Diabetes was not clearly associated with the increased mortality among these older home-dwelling patients., Competing Interests: Declarations. Ethics approval and consent to participate: The survey was conducted in accordance with the ethical principles set by the National Advisory Board on Research Ethics of Finland (15). The study protocol was reviewed and approved by the Research Ethics Committee of the Northern Savo Hospital District, Kuopio, Finland (256/2015) and approved by the Inner Savo Health Care Federation of Municipalities (61 A/2015). By filling out and returning the survey, all participants gave their informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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46. Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization.

Author: Willems SM, Ng NHJ, Fernandez J, Fine RS, Wheeler E, Wessel J, Kitajima H, Marenne G, Sim X, Yaghootkar H, Wang S, Chen S, Chen Y, Chen YI, Grarup N, Li-Gao R, Varga TV, Asimit JL, Feng S, Strawbridge RJ, Kleinbrink EL, Ahluwalia TS, An P, Appel EV, Arking DE, Auvinen J, Bielak LF, Bihlmeyer NA, Bork-Jensen J, Brody JA, Campbell A, Chu AY, Davies G, Demirkan A, Floyd JS, Giulianini F, Guo X, Gustafsson S, Jackson AU, Jakobsdottir J, Järvelin MR, Jensen RA, Kanoni S, Keinanen-Kiukaanniemi S, Li M, Lu Y, Luan J, Manning AK, Marten J, Meidtner K, Mook-Kanamori DO, Muka T, Pistis G, Prins B, Rice KM, Sanna S, Smith AV, Smith JA, Southam L, Stringham HM, Tragante V, van der Laan SW, Warren HR, Yao J, Yiorkas AM, Zhang W, Zhao W, Graff M, Highland HM, Justice AE, Marouli E, Medina-Gomez C, Afaq S, Alhejily WA, Amin N, Asselbergs FW, Bonnycastle LL, Bots ML, Brandslund I, Chen J, Danesh J, de Mutsert R, Dehghan A, Ebeling T, Elliott P, Farmaki AE, Faul JD, Franks PW, Franks S, Fritsche A, Gjesing AP, Goodarzi MO, Gudnason V, Hallmans G, Harris TB, Herzig KH, Hivert MF, Jørgensen T, Jørgensen ME, Jousilahti P, Kajantie E, Karaleftheri M, Kardia SLR, Kinnunen L, Koistinen HA, Komulainen P, Kovacs P, Kuusisto J, Laakso M, Lange LA, Launer LJ, Leong A, Lindström J, Manning Fox JE, Männistö S, Maruthur NM, Moilanen L, Mulas A, Nalls MA, Neville M, Pankow JS, Pattie A, Petersen ERB, Puolijoki H, Rasheed A, Redmond P, Renström F, Roden M, Saleheen D, Saltevo J, Savonen K, Sebert S, Skaaby T, Small KS, Stančáková A, Stokholm J, Strauch K, Tai ES, Taylor KD, Thuesen BH, Tönjes A, Tsafantakis E, Tuomi T, Tuomilehto J, Uusitupa M, Vääräsmäki M, Vaartjes I, Zoledziewska M, Abecasis G, Balkau B, Bisgaard H, Blakemore AI, Blüher M, Boeing H, Boerwinkle E, Bønnelykke K, Bottinger EP, Caulfield MJ, Chambers JC, Chasman DI, Cheng CY, Collins FS, Coresh J, Cucca F, de Borst GJ, Deary IJ, Dedoussis G, Deloukas P, den Ruijter HM, Dupuis J, Evans MK, Ferrannini E, Franco OH, Grallert H, Hansen T, Hattersley AT, Hayward C, Hirschhorn JN, Ikram A, Ingelsson E, Karpe F, Kaw KT, Kiess W, Kooner JS, Körner A, Lakka T, Langenberg C, Lind L, Lindgren CM, Linneberg A, Lipovich L, Liu CT, Liu J, Liu Y, Loos RJF, MacDonald PE, Mohlke KL, Morris AD, Munroe PB, Murray A, Padmanabhan S, Palmer CNA, Pasterkamp G, Pedersen O, Peyser PA, Polasek O, Porteous D, Province MA, Psaty BM, Rauramaa R, Ridker PM, Rolandsson O, Rorsman P, Rosendaal FR, Rudan I, Salomaa V, Schulze MB, Sladek R, Smith BH, Spector TD, Starr JM, Stumvoll M, van Duijn CM, Walker M, Wareham NJ, Weir DR, Wilson JG, Wong TY, Zeggini E, Zonderman AB, Rotter JI, Morris AP, Boehnke M, Florez JC, McCarthy MI, Meigs JB, Mahajan A, Scott RA, Gloyn AL, and Barroso I
Abstract: Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways., Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses., Results: Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology., Conclusions: Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries., Competing Interests: Competing interests: Rebecca S. Fine: Rebecca S. Fine is currently employed by Vertex Pharmaceuticals Incorporated. Audrey Y Chu: Currently employed by GlaxoSmithkline. Dennis O. Mook-Kanamori: Dennis Mook-Kanamori is working as a part-time clinical research consultant for Metabolon, Inc. Paul W. Franks: PWF has been a paid consultant for Eli Lilly and Sanofi Aventis and has received research support from several pharmaceutical companies as part of a European Union Innovative Medicines Initiative (IMI) project. Mike A. Nalls: Dr. Mike A. Nalls is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. Dr. Nalls also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. Mark J. Caulfield: MJC is Chief Scientist for Genomics England, a UK government company. Joel N. Hirschhorn: JHN is on the scientific advisory board of Camp4 Therapeutics. Erik Ingelsson: Erik Ingelsson is now an employee of GlaxoSmithKline. Anubha Mahajan: Anubha Mahajan is an employee of Genentech since January 2020, and a holder of Roche stock. Mark I McCarthy: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. MMcC has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MMcC is an employee of Genentech, and a holder of Roche stock. Inês Barroso: IB and spouse declare stock ownership in GlaxoSmithkline and Incyte Ltd. James B. Meigs: JBM serves as an Academic Associate for Quest Diagnostics R&D Bruce M Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Dr. Sander W. van der Laan has received Roche funding for unrelated work. Matthias Blüher received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis, Pfizer and Sanofi. Vinicius Tragante: VT became an employee of deCODE genetics/Amgen Inc. after the conclusion of this work Dr Franco is employed by ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.) and Metagenics., (Copyright: © 2023 Willems SM et al.)
Published: 2023
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47. Use of primary health care services among older patients with and without diabetes.

Author: Aro AK, Karjalainen M, Tiihonen M, Kautiainen H, Saltevo J, Haanpää M, and Mäntyselkä P
Subjects: Appointments and Schedules, Health Services, Humans, Primary Health Care methods, Surveys and Questionnaires, Diabetes Mellitus, Type 2 epidemiology
Abstract: Background: The aim of this study was to compare the utilization of primary healthcare services by older patients with and without type 2 diabetes., Methods: Electronic patient records were used to identify persons over 65 years of age with a diagnosis of diabetes. Two age- and sex-adjusted controls without diabetes were extracted for each person with diagnosis of diabetes. A health questionnaire was sent by mail to 527 people with diabetes and 890 controls. Of the persons who answered the questionnaire, 518 persons were randomly selected to participate in a health examination. The study group in this analysis consisted of 187 persons with diabetes and 176 persons without diabetes who attended the health examination. The data on primary health care utilization were extracted from electronic patient records one year before and one after the health examination., Results: Before the onset of the study, the patients with diabetes had more doctor's appointments (p < 0.001), nurse's appointments (< 0.001) and laboratory tests taken (p < 0.001) than those without diabetes After 1-year follow-up period the patients with diabetes had more doctor's appointments (p = 0.002), nurse's appointments (p = 0.006), laboratory tests taken (p = 0.006) and inpatient care at the community hospital (p = 0.004) than patients without a diagnosis of type 2 diabetes. The use of the community hospital increased significantly among patients with diabetes (ratio 2.50; 95% Cl 1.16-5.36) but not by patients without diabetes (ratio 0.91; 95% Cl 0.40.2.06). The number of nurse's appointments increased for patients without diabetes (ratio 1.31; 95% Cl 1.07-1.60) but not for those with diabetes (ratio 1.04; 95% Cl 0.88-1.24)., Conclusions: Patients with diabetes visit more often physicians and nurses compared with those without diabetes. During a 1-year follow-up, the use of community hospital care increased significantly among patients with diabetes. In addition to focusing on prevention and care of diabetes, these results suggest the importance of diabetes in planning community-based health care services., (© 2022. The Author(s).)
Published: 2022
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48. Factors predicting 31-year survival among a population cohort in Northern Finland.

Author: Perkkiö Y, Auvinen J, Timonen M, Jokelainen J, Valkeapää N, Koiranen M, Saltevo J, and Keinänen-Kiukaanniemi S
Subjects: Cohort Studies, Female, Finland epidemiology, Humans, Male, Proportional Hazards Models, Risk Factors, Cardiovascular Diseases
Abstract: We evaluated the survival of a subarctic population and the significance of traditional risk factors for mortality, causes of death and their seasonal variation from the period of 1984-2014. By the end of 2014 (follow-up), 644 (34.4% from 1,869) participants had died (42.1% of cardiovascular causes, 22.4% of neoplastic diseases). The average age at death±SD was 74.6±11.4 years for women (n=284) and 70.2±12.0 years for men (n=360). After adjusting for baseline age, the major risk factors predicting death were male sex (hazard ratio [HR] 1.80; 95% confidence interval [CI] 1.54-2.10), current smoking (HR 1.85; 95% CI 1.58-2.17), obesity (HR 1.75; 95% CI 1.45-2.12), high blood pressure (HR 1.46; 95% CI 1.24-1.72), cardiovascular disease (HR 1.62; 95% CI 1.36-1.93) and depression (HR 1.61; 95% CI 1.21-2.14) at baseline.The most common causes of death and the main risk factors predicting death in this population were the same as reported globally. Lifestyle factors had an important impact in predicting survival. The most common causes of death were the same for men and women. There was no significant difference in overall mortality rate between winter and summer, but cerebrovascular and pulmonary causes of death were more common during winter.
Published: 2021
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49. Long-term outcomes of lifestyle intervention to prevent type 2 diabetes in people at high risk in primary health care.

Author: Rintamäki R, Rautio N, Peltonen M, Jokelainen J, Keinänen-Kiukaanniemi S, Oksa H, Saaristo T, Puolijoki H, Saltevo J, Tuomilehto J, Uusitupa M, and Moilanen L
Subjects: Humans, Life Style, Primary Health Care, Weight Loss, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 prevention & control, Pharmaceutical Preparations
Abstract: Aims: The Finnish National Diabetes Prevention Program (FIN-D2D) was the first large-scale diabetes prevention program in a primary health care setting in the world. The risk reduction of type 2 diabetes was 69% after one-year intervention in high-risk individuals who were able to lose 5% of their weight. We investigated long-term effects of one-year weight change on the incidence of type 2 diabetes, cardiovascular events, and all-cause mortality., Methods: A total of 10,149 high-risk individuals for type 2 diabetes were identified in primary health care centers and they were offered lifestyle intervention to prevent diabetes. Of these individuals who participated in the baseline screening, 8353 had an oral glucose tolerance test (OGTT). Complete follow-up data during one-year intervention were available for 2730 individuals and those were included in the follow-up analysis. The long-term outcome events were collected from national health registers after the median follow-up of 7.4 years., Results: Among individuals who lost weight 2.5-4.9% and 5% or more during the first year, the hazard ratio for the incidence of drug-treated diabetes was 0.63 (95% CI 0.49-0.81, p = 0.0001), and 0.71 (95% CI 0.56-0.90, p = 0.004), respectively, compared with those with stable weight. There were no significant differences in cardiovascular events or all-cause mortality among study participants according to one-year weight changes., Conclusions: High-risk individuals for type 2 diabetes who achieved a moderate weight loss by one-year lifestyle counseling in primary health care had a long-term reduction in the incidence of drug-treated type 2 diabetes. The observed moderate weight loss was not associated with a reduction in cardiovascular events., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2021
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50. Use of pain relieving drugs in community-dwelling older people with and without type 2 diabetes.

Author: Karjalainen M, Kautiainen H, Saltevo J, Haanpää M, Mäntyselkä P, and Tiihonen M
Subjects: Aged, Analgesics, Opioid, Humans, Independent Living, Analgesics therapeutic use, Diabetes Mellitus, Type 2 epidemiology, Pain drug therapy
Abstract: Aims: To analyze the use of pain medication among community-dwelling people aged 65 years or older with and without type 2 diabetes in primary care., Methods: A total of 187 patients with and 176 patients without diabetes were randomly selected from a primary care sample of 389 patients with diabetes and 604 age- and gender-matched controls. Pain status was defined as no pain, nociceptive pain or neuropathic pain. Pain medication (paracetamol, NSAID, opioids, neuropathic pain medication) use was based on electronic patient records and checked by a physician during a health examination., Results: Some pain was present in 90 (51%) patients without and in 106 (57%) patients with diabetes (p = 0.55). Of the patients without diabetes, 109 (62%) and with diabetes 123 (66%) used some pain medication (p = 0.45). The respective proportions for the regular use were 13% and 11% and for the as needed use 56% and 61%. Diabetes was not associated with any of the pain medications used. The use of pain-relieving drugs was most common for neuropathic pain., Conclusions: The present study indicated that community-dwelling people with and without diabetes used pain medication similarly. Pain medication was used mostly as needed instead of being regular., (Copyright © 2020 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)
Published: 2020
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