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1. Factors associated with the night-time index fall in an older hip fracture population

Author: Nuotio, M. and Luukkaala, T.
Published: 2015
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2. Association of nutritional status as measured by the Mini-Nutritional Assessment short form with changes in mobility, institutionalization and death after hip fracture

Author: Nuotio, M., Tuominen, P., and Luukkaala, T.
Subjects: Nutrition -- Product/Service Evaluations, Hip joint -- Fractures, Food/cooking/nutrition, Health
Abstract: BACKGROUND/OBJECTIVES: We examined the association of nutritional status as measured by the Mini-Nutritional Assessment Short Form (MNA-SF) with changes in mobility, institutionalization and death after hip fracture. SUBJECTS/METHODS: Population-based prospective data were collected on 472 out of 693 consecutive hip fracture patients aged 65 years and over between January 2010 and December 2012. Declined vs same or improved mobility level, institutionalization and death during the 4-month follow-up were the outcomes. Age, gender, American Society of Anesthesiologists scores, pre-fracture diagnosis of a memory disorder, mobility level, living arrangements and MNA-SF scores at baseline were the independent variables. Age-adjusted and multivariate logistic regression and Cox proportional hazards models were conducted. RESULTS: At baseline, 41 (9%) patients were malnourished and 200 (42%) patients at risk of malnutrition according to the MNA-SF. During the follow-up, 90 (19%) had died. In the multivariate Cox proportional hazards model, malnutrition (hazard ratio 2.16;95% confidence interval (CI) 1.07-4.34) was associated with mortality. In the multivariate binary logistic regression analyses, risk of malnutrition (odds ratios (OR) 2.42;95% CI 1.25-4.66) and malnutrition (OR 6.10;95% CI 2.01-18.5) predicted institutionalization. Risk of malnutrition (OR 2.03;95% CI 1.24-3.31) was associated with decline in the mobility level. CONCLUSIONS: Malnutrition or risk of malnutrition as measured by the MNA-SF were independent predictors of negative outcomes after hip fracture. Patients classified as being at risk of malnutrition by the MNA-SF may constitute a patient population with mild-to-moderate malnutrition and may require specific attention when nutritional interventions are designed after hip fracture. European Journal of Clinical Nutrition (2016) 70, 393-398; doi: 10.1038/ejcn.2015.174;published online 21 October 2015, INTRODUCTION Hip fractures are a source of substantial morbidity, disability and mortality in ageing populations. (1, 2) The quality of life and economic consequences are well known and recognized. (3) [...]
Published: 2016
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3. Nutritional aspects in perioperative care

Author: Saarnio, J. (Juha), Nuotio, M. (Maria), Helminen, H. (Heli), Saarnio, J. (Juha), Nuotio, M. (Maria), and Helminen, H. (Heli)
Abstract: This thesis investigates the role of nutrition in perioperative care; the effects of preoperative carbohydrate loading and whether nutrition screening tests can detect malnutrition and determine the prognosis of recovery from hip fracture in older patients. In the randomized, controlled trial (RCT) overnight fasting was compared to overnight intravenous (iv) glucose and carbohydrate-rich drink (CHD) in the morning. The patients’ subjective feelings of wellbeing were elicited using a visual analogue scale (VAS). In the second RCT overnight fasting was compared to CHD in day-case cholecystectomy patients. In the observational nutrition studies status of hip fracture patients was evaluated using the Mini Nutritional Assessment (MNA) short (SF) and long version (LF), serum albumin (S-Alb) and the Nutritional Risk Screening 2002 (NRS2002). The outcomes were the length of hospitalization, readmissions, changes in mobility and living arrangements and mortality. The changes in nutritional status and its association with the comprehensive geriatric assessment (CGA) were evaluated after six months follow-up. CHD relieved thirst better than iv solution. The CHD group was less hungry than the fasting group before the operation. Day-case cholecystectomy patients did not benefit from CHD. Of the hip fracture patients 25%, 45% and 55 % had poor nutritional status at fractura time according to the NRS2002, S-Alb and MNA tests, respectively. Poor nutritional status in the MNAs predicted prolonged hospitalization, readmissions, need for more supportive living arrangements, mobility limitations and mortality. Low S-Alb predicted mortality. The NRS2002 predicted the outcomes poorly. There was a clear deterioration in nutritional status during follow-up. Many factors in the CGA were associated with poor nutrition status: depressed mood, cognitive impairment, weakened grip strength, difficulties in activities of daily living. CHD is safe and may promote wellbeing while waiting f, Tiivistelmä Väitöskirjassa tarkastellaan ravitsemusnäkökulmia liittyen leikkaushoitoon. Kahdessa satunnaistetussa, kontrolloidussa tutkimuksessa (RCT) verrattiin hiilihydraattitankkausta paastoamiseen ennen suunniteltua leikkausta. Toisena aiheena tutkittiin ravitsemusseulontatestien toimivuuttaa tunnistaa vanhuksen vajaaravitsemus ja ennustaa toipumista lonkkamurtumasta. Verrattiin suonensisäisen (iv), juomalla annetun hiilihydraattitankkauksen (CHD) ja paaston vaikutusta vointiin leikkausta odottaessa. Vointia arvioitiin Visual Analogue Scale (VAS) mittarilla. Toisessa osatyössä verrattiin paaston ja CHD vaikutusta päiväkirurgisilla sappileikkauspotilailla. Lonkkamurtumapotilaiden ravitsemustilaa arvioitiin neljällä testillä: Mini Nutritional Assessment (MNA) lyhyt (SF) ja pitkä versio (LF), seerumin albumiini (S-Alb) ja Nutritional Risk Screening 2002 (NRS2002). Toipumismittareina käytettiin sairaalahoidon pituutta, uusia hoitojaksoja, liikuntakyvyn, asumismuodon muutosta ja kuolleisuutta. Lisäksi selvitettiin ravitsemustilan muutosta ja yhteyttä laajan geriatrisen arvioinnin (CGA) tuloksiin puoli vuotta murtumasta. CHD lievensi janoa paremmin kuin iv-liuos. CHD:tä saaneet olivat ennen leikkausta vähemmän nälkäisiä kuin paastonneet. Päiväkirurgiset potilaat eivät hyötyneet CHD:stä. Ravitsemusseulontatutkimuksissa oli murtumahetkellä potilaista vajaaravitsemusriskissä tai vajaaravittuja 25 % NRS2002-testillä, 45 % S-Alb:lla ja 55 % MNA-testeillä arvioituna. Heikentynyt ravitsemustila MNA-testien perusteella ennusti sairaalahoidon pitkittymistä, uusia hoitojaksoja, tuetumman asumismuodon tarvetta, liikuntakyvyn heikkenemistä ja kuolleisuutta. Matala S-Alb ennusti kuolleisuutta. NRS2002 ennusti huonosti toipumistuloksia. Ravitsemustila huononi useilla seuranta-aikana ja oli yhteydessä masennukseen, muistisairauteen, heikkoon käden puristusvoimaan ja heikentyneisiin tuloksiin toimintakykytesteissä CGA:ssa. CHD leikkauspäivän aamuna on turvallinen ja voi vähentää epäm
Published: 2020

4. An epigenome-wide association study of metabolic syndrome and its components

Author: Nuotio, M.-L. (Marja-Liisa), Natalia Pervjakova, N. P. (Natalia Pervjakova), Joensuu, A. (Anni), Karhunen, V. (Ville), Hiekkalinna, T. (Tero), Milani, L. (Lili), Kettunen, J. (Johannes), Järvelin, M.-R. (Marjo-Riitta), Jousilahti, P. (Pekka), Metspalu, A. (Andres), Salomaa, V. (Veikko), Kristiansson, K. (Kati), Perola, M. (Markus), Nuotio, M.-L. (Marja-Liisa), Natalia Pervjakova, N. P. (Natalia Pervjakova), Joensuu, A. (Anni), Karhunen, V. (Ville), Hiekkalinna, T. (Tero), Milani, L. (Lili), Kettunen, J. (Johannes), Järvelin, M.-R. (Marjo-Riitta), Jousilahti, P. (Pekka), Metspalu, A. (Andres), Salomaa, V. (Veikko), Kristiansson, K. (Kati), and Perola, M. (Markus)
Abstract: The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP —previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level (P = 1.80 × 10⁻⁸). Cg06500161 in gene ABCG1 associated both with serum triglycerides (P = 5.36 × 10⁻⁹) and waist circumference (P = 5.21 × 10⁻⁹). The previously identified type 2 diabetes–associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time (P = 2.24 × 10⁻⁷). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified (P = 7.81 × 10⁻⁸). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.
Published: 2020

5. European postgraduate curriculum in geriatric medicine developed using an international modified Delphi technique

Author: Roller-Wirnsberger, R., Masud, T., Vassallo, M., Zobl, M., Reiter, R., Van Den Noortgate, N., Petermans, J., Petrov, I., Topinkova, E., Andersen-Ranberg, K., Saks, K., Nuotio, M., Bonin-Guillaume, S., Luttje, D., Mestheneos, E., Szekacs, B., Jonsdottir, A.B., O'Neill, D., Cherubini, A., Macijauskiene, J., Leners, J.C., Fiorini, A., Iersel, M.B. van, Ranhoff, A.H., Kostka, T., Duque, S., Prada, G.I., Davidovic, Mladen, Krajcik, S., Kolsek, M., Del Nozal, J.M., Ekdahl, A.W., Munzer, T., Savas, S., Knight, P., Gordon, A., Singler, K., Roller-Wirnsberger, R., Masud, T., Vassallo, M., Zobl, M., Reiter, R., Van Den Noortgate, N., Petermans, J., Petrov, I., Topinkova, E., Andersen-Ranberg, K., Saks, K., Nuotio, M., Bonin-Guillaume, S., Luttje, D., Mestheneos, E., Szekacs, B., Jonsdottir, A.B., O'Neill, D., Cherubini, A., Macijauskiene, J., Leners, J.C., Fiorini, A., Iersel, M.B. van, Ranhoff, A.H., Kostka, T., Duque, S., Prada, G.I., Davidovic, Mladen, Krajcik, S., Kolsek, M., Del Nozal, J.M., Ekdahl, A.W., Munzer, T., Savas, S., Knight, P., Gordon, A., and Singler, K.
Abstract: Contains fulltext : 208089.pdf (publisher's version ) (Open Access), BACKGROUND: the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations. METHODS: under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators. RESULTS: the final recommendations include four different domains: 'General Considerations' on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), 'Knowledge in patient care' (36 sub-items), 'Additional Skills and Attitude required for a Geriatrician' (9 sub-items) and a domain on 'Assessment of postgraduate education: which items are important for the transnational comparison process' (1 item). CONCLUSION: the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states.
Published: 2019

6. Predictive value of the mini-nutritional assessment short form (MNA-SF) and nutritional risk screening (NRS2002) in hip fracture

Author: Helminen, H. (Heli), Luukkaala, T. (Tiina), Saarnio, J. (Juha), Nuotio, M. S. (Maria S.), Helminen, H. (Heli), Luukkaala, T. (Tiina), Saarnio, J. (Juha), and Nuotio, M. S. (Maria S.)
Abstract: Background/Objectives: To examine Mini-Nutritional Assessment short form (MNA-SF) and Nutritional Risk Screening 2002 (NRS2002) as prognostic indicators of postoperative complications, length of hospital stay (LOS), readmissions, mobility, living arrangements and mortality after hip fracture. Subjects/Methods: Population-based prospective data were collected on 265 consecutive hip fracture patients aged 65 and over. Nutritional status according to MNA-SF and NRS2002 was assessed on admission. Outcomes were postoperative complications, LOS, readmissions and mortality 1 and 4 months post fracture and changes in mobility level and living arrangements 4 months post fracture. Results: At baseline, 18 (7%) patients were malnourished and 108 (41%) at risk of malnutrition according to MNA-SF. According to NRS2002, 11 (4%) patients were at severe risk and 56 (21%) patients at moderate risk of malnutrition. Only MNA-SF predicted mortality, LOS and readmissions. Both instruments proved ineffective in predicting changes in mobility level and living arrangements. Conclusions: MNA-SF is superior to NRS2002 in predicting short-term hip fracture outcomes.
Published: 2019

7. Urgency, urge incontinence and voiding symptoms in men and women aged 70 years and over

Author: Nuotio, M., Jylhä, M., Luukkaala, T., and Tammela, T.L.J.
Published: 2002

8. Association between urinary incontinence and frailty: a systematic review and meta-analysis

Author: Veronese, N., Soysal, P., Stubbs, B., Marengoni, A., Demurtas, J., Maggi, S., Petrovic, M., Verdejo-Bravo, C., Aharony, L., De Cock, J., Nuotio, M. S., Pedone, C., Rifel, J., Vande Walle, N., Velghe, A., Vella, A., Solmi, M., Koyanagi, A., Thompson, T., Beudart, C., Bruyère, O., Torbahn, G., Firth, J., Smith, L., The Special Interest Group on Urinary Incontinence, The Special Interest Group of Systematic Reviews and Meta-Analysis for Healthy Aging, European Geriatric Medicine Society (EuGMS), SOYSAL, PINAR, Veronese, N., Soysal, P., Stubbs, B., Marengoni, A., Demurtas, J., Maggi, S., Petrovic, M., Verdejo-Bravo, C., Aharony, L., De Cock, J., Nuotio, M.S., Pedone, C., Rifel, J., Vande Walle, N., Velghe, A., Vella, A., Solmi, M., Koyanagi, A., Thompson, T., Beudart, C., Bruyère, O., Torbahn, G., Firth, J., Smith, L., The Special Interest Group on Urinary Incontinence, and The Special Interest Group of Systematic Reviews and Meta-Analysis for Healthy Aging, European Geriatric Medicine Society (EuGMS)
Subjects: Gerontology, Longitudinal study, a systematic review and meta-analysis-, EUROPEAN GERIATRIC MEDICINE, cilt.9, ss.571-578, 2018 [Veronese N., SOYSAL P., Stubbs B., Marengoni A., Demurtas J., Maggi S., Petrovic M., Verdejo-Bravo C., -Association between urinary incontinence and frailty], business.industry, Confounding, Psychological intervention, Urinary incontinence, Odds ratio, medicine.disease, Frailty · Urinary incontinence · Meta-analysis · Aged, Comorbidity, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Meta-analysis, medicine, 030212 general & internal medicine, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Purpose: Urinary incontinence (UI) and frailty are common geriatric syndromes. Although literature increasingly supports a relationship between these two conditions, no systematic review and meta-analysis has been performed on this topic. Therefore, we aimed to investigate the potential association between UI and frailty, through a meta-analytic approach. Methods: A systematic search in major databases was undertaken until 15th March 2018 for studies reporting the association between UI and frailty. The prevalence of UI in people with frailty (vs. those without) was pooled through an odds ratio (OR) and 95% confidence intervals (CIs), with a random-effects model. The other outcomes were summarized descriptively. Results: Among 828 papers, 11 articles were eligible, including 3784 participants (mean age 78.2years; 55.1% women). The prevalence of UI was 39.1% in people with frailty and 19.4% in those without. A meta-analysis with five studies (1540 participants) demonstrated that UI was over twice as likely in frail people versus those without (OR 2.28; 95% CI 1.35–3.86; I2 = 61%). One cross-sectional study, adjusting for potential confounders and one longitudinal study confirmed that UI is significantly associated with frailty. In two cross-sectional studies, using adjusted analyses, frailty was more common in people with UI. Conclusion: Urinary incontinence is twice as common in older people with frailty compared to older people without frailty. Screening and the development of interventions for UI and frailty could prove useful for this common comorbidity. © 2018, European Geriatric Medicine Society.
Published: 2018

9. Lateral and Posterior Approaches in Hemiarthroplasty

Author: Hongisto, M. T., primary, Nuotio, M. S., additional, Luukkaala, T., additional, Väistö, O., additional, and Pihlajamäki, H. K., additional
Published: 2018
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10. Gene × dietary pattern interactions in obesity: Analysis of up to 68 317 adults of European ancestry

Author: Nettleton, J.A., Follis, J.L. (Jack ), Ngwa, J.S., Smith, C.E. (Caren), Ahmad, S. (Shafqat), Tanaka, T. (Toshiko), Wojczynski, M.K. (Mary ), Voortman, R.G. (Trudy), Lemaitre, R.N. (Rozenn ), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Houston, D.K., Perälä, M.-M. (Mia-Maria), Qi, Q., Sonestedt, E. (Emily), Manichaikul, A. (Ani), Kanoni, S. (Stavroula), Ganna, A. (Andrea), Mikkilä, V. (Vera), North, K.E. (Kari), Siscovick, D.S. (David), Harald, K. (Kennet), McKeown, N.M. (Nicola ), Johansson, I. (Ingegerd), Rissanen, H. (Harri), Liu, Y. (YongMei), Lahti, J. (Jari), Hu, F.B. (Frank), Bandinelli, S. (Stefania), Rukh, G. (Gull), Rich, S.S. (Stephen S.), Booij, L. (Lisanne), Dmitriou, M. (Maria), Ax, E. (Erika), Raitakari, O.T. (Olli T.), Mukamal, K. (Kenneth), Männistö, S. (Satu), Hallmans, G. (Göran), Jula, A. (Antti), Ericson, U. (Ulrika), Jacobs, D.R. (David), Rooij, F.J.A. (Frank) van, Deloukas, P. (Panagiotis), Sjøgren, P. (Per), Kähönen, M. (Mika), Djoussé, L. (Luc), Perola, M. (Markus), Barroso, I.E. (Inês), Hofman, A. (Albert), Stirrups, K. (Kathy), Viikari, J. (Jorma), Uitterlinden, A.G. (André), Kalafati, I.-P. (Ioanna-Panagiota), Franco, O.H. (Oscar), Mozaffarian, D. (Dariush), Salomaa, V. (Veikko), Borecki, I.B. (Ingrid), Knekt, P., Kritchevsky, S.B. (Stephen), Hagen, K. (Knut), Dedoussis, G.V. (George), Qi, L. (Lu), Ferrucci, L. (Luigi), Orho-Melander, M. (Marju), Zillikens, M.C. (Carola), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Renström, F. (Frida), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), Franks, P.W. (Paul), Nettleton, J.A., Follis, J.L. (Jack ), Ngwa, J.S., Smith, C.E. (Caren), Ahmad, S. (Shafqat), Tanaka, T. (Toshiko), Wojczynski, M.K. (Mary ), Voortman, R.G. (Trudy), Lemaitre, R.N. (Rozenn ), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Houston, D.K., Perälä, M.-M. (Mia-Maria), Qi, Q., Sonestedt, E. (Emily), Manichaikul, A. (Ani), Kanoni, S. (Stavroula), Ganna, A. (Andrea), Mikkilä, V. (Vera), North, K.E. (Kari), Siscovick, D.S. (David), Harald, K. (Kennet), McKeown, N.M. (Nicola ), Johansson, I. (Ingegerd), Rissanen, H. (Harri), Liu, Y. (YongMei), Lahti, J. (Jari), Hu, F.B. (Frank), Bandinelli, S. (Stefania), Rukh, G. (Gull), Rich, S.S. (Stephen S.), Booij, L. (Lisanne), Dmitriou, M. (Maria), Ax, E. (Erika), Raitakari, O.T. (Olli T.), Mukamal, K. (Kenneth), Männistö, S. (Satu), Hallmans, G. (Göran), Jula, A. (Antti), Ericson, U. (Ulrika), Jacobs, D.R. (David), Rooij, F.J.A. (Frank) van, Deloukas, P. (Panagiotis), Sjøgren, P. (Per), Kähönen, M. (Mika), Djoussé, L. (Luc), Perola, M. (Markus), Barroso, I.E. (Inês), Hofman, A. (Albert), Stirrups, K. (Kathy), Viikari, J. (Jorma), Uitterlinden, A.G. (André), Kalafati, I.-P. (Ioanna-Panagiota), Franco, O.H. (Oscar), Mozaffarian, D. (Dariush), Salomaa, V. (Veikko), Borecki, I.B. (Ingrid), Knekt, P., Kritchevsky, S.B. (Stephen), Hagen, K. (Knut), Dedoussis, G.V. (George), Qi, L. (Lu), Ferrucci, L. (Luigi), Orho-Melander, M. (Marju), Zillikens, M.C. (Carola), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Renström, F. (Frida), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), and Franks, P.W. (Paul)
Abstract: Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS
Published: 2015
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11. Age- and sex-specific causal effects of adiposity on cardiovascular risk factors

Author: Fall, M. (Magnus), Hägg, S. (Sara), Ploner, A. (Alexander), Mägi, R. (Reedik), Fischer, K. (Krista), Draisma, G. (Gerrit), Sarin, A.-P., Benyamin, B. (Beben), Ladenvall, C. (Claes), Åkerlund, M. (Mikael), Kals, M. (Mart), Esko, T. (Tõnu), Nelson, C.P. (Christopher P.), Kaakinen, M. (Marika), Huikari, V. (Ville), Mangino, M. (Massimo), Meirhaeghe, A. (Aline), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Kobl, M. (Michael), Grallert, H. (Harald), Dehghan, A. (Abbas), Kuningas, M. (Maris), Vries, P.S. (Paul) de, Bruijn, R.F.A.G. (Renée) de, Willems, S.M. (Sara), Heikkilä, K. (Kauko), Silventoinen, K. (Karri), Pietilainen, K.H. (Kirsi Hannele), Legry, V. (Vanessa), Giedraitis, V. (Vilmantas), Goumidi, L. (Louisa), Syvanen, A.C., Strauch, K. (Konstantin), Koenig, W. (Wolfgang), Lichtner, P. (Peter), Herder, C. (Christian), Palotie, A. (Aarno), Menni, C. (Cristina), Uitterlinden, A.G. (André), Kuulasmaa, K. (Kari), Havulinna, A.S. (Aki), Moreno, L. (Luis), Gonzalez-Gross, M. (Marcela), Evans, A. (Alun), Tregouet, D.-A. (David-Alexandre), Yarnell, J.W.G. (John W.), Virtamo, J. (Jarmo), Ferrieres, J. (Jean), Veronesi, G. (Giovanni), Perola, M. (Markus), Arveiler, D. (Dominique), Brambilla, P. (Paolo), Lind, L. (Lars), Kaprio, J. (Jaakko), Hofman, A. (Albert), Stricker, B.H.Ch. (Bruno), Duijn, C.M. (Cornelia) van, Ikram, M.A. (Arfan), Franco, O.H. (Oscar), Cottel, D. (Dominique), Dallongeville, J., Hall, A.S. (Alistair), Jula, A. (Antti), Tobin, M.D. (Martin), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Gieger, C. (Christian), Samani, N.J. (Nilesh), Montgomery, G.W. (Grant), Whitfield, J. (John), Martin, N.G. (Nicholas), Groop, L. (Leif), Spector, T.D. (Timothy), Magnusson, P.K. (Patrik), Amouyel, P. (Philippe), Boomsma, D.I. (Dorret), Nilsson, P. (Peter), Jarvelin, M.-R. (Marjo-Riitta), Lyssenko, V. (Valeriya), Metspalu, A. (Andres), Strachan, D.P. (David), Salomaa, V. (Veikko), Ripatti, S. (Samuli), Pedersen, N.L. (Nancy), Prokopenko, I. (Inga), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Fall, M. (Magnus), Hägg, S. (Sara), Ploner, A. (Alexander), Mägi, R. (Reedik), Fischer, K. (Krista), Draisma, G. (Gerrit), Sarin, A.-P., Benyamin, B. (Beben), Ladenvall, C. (Claes), Åkerlund, M. (Mikael), Kals, M. (Mart), Esko, T. (Tõnu), Nelson, C.P. (Christopher P.), Kaakinen, M. (Marika), Huikari, V. (Ville), Mangino, M. (Massimo), Meirhaeghe, A. (Aline), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Kobl, M. (Michael), Grallert, H. (Harald), Dehghan, A. (Abbas), Kuningas, M. (Maris), Vries, P.S. (Paul) de, Bruijn, R.F.A.G. (Renée) de, Willems, S.M. (Sara), Heikkilä, K. (Kauko), Silventoinen, K. (Karri), Pietilainen, K.H. (Kirsi Hannele), Legry, V. (Vanessa), Giedraitis, V. (Vilmantas), Goumidi, L. (Louisa), Syvanen, A.C., Strauch, K. (Konstantin), Koenig, W. (Wolfgang), Lichtner, P. (Peter), Herder, C. (Christian), Palotie, A. (Aarno), Menni, C. (Cristina), Uitterlinden, A.G. (André), Kuulasmaa, K. (Kari), Havulinna, A.S. (Aki), Moreno, L. (Luis), Gonzalez-Gross, M. (Marcela), Evans, A. (Alun), Tregouet, D.-A. (David-Alexandre), Yarnell, J.W.G. (John W.), Virtamo, J. (Jarmo), Ferrieres, J. (Jean), Veronesi, G. (Giovanni), Perola, M. (Markus), Arveiler, D. (Dominique), Brambilla, P. (Paolo), Lind, L. (Lars), Kaprio, J. (Jaakko), Hofman, A. (Albert), Stricker, B.H.Ch. (Bruno), Duijn, C.M. (Cornelia) van, Ikram, M.A. (Arfan), Franco, O.H. (Oscar), Cottel, D. (Dominique), Dallongeville, J., Hall, A.S. (Alistair), Jula, A. (Antti), Tobin, M.D. (Martin), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Gieger, C. (Christian), Samani, N.J. (Nilesh), Montgomery, G.W. (Grant), Whitfield, J. (John), Martin, N.G. (Nicholas), Groop, L. (Leif), Spector, T.D. (Timothy), Magnusson, P.K. (Patrik), Amouyel, P. (Philippe), Boomsma, D.I. (Dorret), Nilsson, P. (Peter), Jarvelin, M.-R. (Marjo-Riitta), Lyssenko, V. (Valeriya), Metspalu, A. (Andres), Strachan, D.P. (David), Salomaa, V. (Veikko), Ripatti, S. (Samuli), Pedersen, N.L. (Nancy), Prokopenko, I. (Inga), McCarthy, M.I. (Mark), and Ingelsson, E. (Erik)
Abstract: Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.
Published: 2015
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12. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, 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Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Cox, D, Dimitriou, M, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Peden, J, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Basart, H, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Goodall, A, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kim, H, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Hovingh, G, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Kathiresan, S, Roberts, R, Schunkert, H, 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Lacroix, A, Lee, S, Leung, P, Lewis, J, Masi, L, Mencej Bedrac, S, Nguyen, T, Nogues, X, Patel, M, Prezelj, J, Scollen, S, Siggeirsdottir, K, Svensson, O, Trummer, O, van Schoor, N, Woo, J, Zhu, K, Balcells, S, Brandi, M, Cheng, S, Christiansen, C, Cooper, C, Frost, M, Goltzman, D, González Macías, J, Karlsson, M, Khusnutdinova, E, Koh, J, Kollia, P, Langdahl, B, Leslie, W, Lips, P, Ljunggren, Ö, Lorenc, R, Marc, J, Mellström, D, Obermayer Pietsch, B, Olmos, J, Pettersson Kymmer, U, Reid, D, Riancho, J, Rousseau, F, Tang, N, Urreizti, R, Van Hul, W, Zarrabeitia, M, Castano Betancourt, M, Herrera, L, Ingvarsson, T, Johannsdottir, H, Kwan, T, Li, R, Luben, R, Medina Gómez, C, Palsson, S, Reppe, S, Sigurdsson, G, van Meurs, J, Verlaan, D, Williams, F, Zhou, Y, Gautvik, K, Raychaudhuri, S, Cauley, J, Clark, G, Cummings, S, Danoy, P, Dennison, E, Eastell, R, Eisman, J, Jackson, R, Jones, G, Khaw, K, Mccloskey, E, Nandakumar, K, Peacock, M, Pols, H, Prince, R, Reid, I, Robbins, J, 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Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

13. Age- And sex-specific causal effects of adiposity on cardiovascular risk factors

Author: Fall, T, Hägg, S, Ploner, A, Mägi, R, Fischer, K, Draisma, H, Sarin, A, Benyamin, B, Ladenvall, C, Åkerlund, M, Kals, M, Esko, T, Nelson, C, Kaakinen, M, Huikari, V, Mangino, M, Meirhaeghe, A, Kristiansson, K, Nuotio, M, Kobl, M, Grallert, H, Dehghan, A, Kuningas, M, de Vries, P, de Bruijn, R, Willems, S, Heikkilä, K, Silventoinen, K, Pietiläinen, K, Legry, V, Giedraitis, V, Goumidi, L, Syvänen, A, Strauch, K, Koenig, W, Lichtner, P, Herder, C, Palotie, A, Menni, C, Uitterlinden, A, Kuulasmaa, K, Havulinna, A, Moreno, L, Gonzalez Gross, M, Evans, A, Tregouet, D, Yarnell, J, Virtamo, J, Ferrières, J, Veronesi, G, Perola, M, Arveiler, D, Brambilla, P, Lind, L, Kaprio, J, Hofman, A, Stricker, B, van Duijn, C, Ikram, M, Franco, O, Cottel, D, Dallongeville, J, Hall, A, Jula, A, Tobin, M, Penninx, B, Peters, A, Gieger, C, Samani, N, Montgomery, G, Whitfield, J, Martin, N, Groop, L, Spector, T, Magnusson, P, Amouyel, P, Boomsma, D, Nilsson, P, Järvelin, M, Lyssenko, V, Metspalu, A, Strachan, D, Salomaa, V, Ripatti, S, Pedersen, N, Prokopenko, I, Mccarthy, M, Ingelsson, E, BRAMBILLA, PAOLO, Ingelsson, E., Fall, T, Hägg, S, Ploner, A, Mägi, R, Fischer, K, Draisma, H, Sarin, A, Benyamin, B, Ladenvall, C, Åkerlund, M, Kals, M, Esko, T, Nelson, C, Kaakinen, M, Huikari, V, Mangino, M, Meirhaeghe, A, Kristiansson, K, Nuotio, M, Kobl, M, Grallert, H, Dehghan, A, Kuningas, M, de Vries, P, de Bruijn, R, Willems, S, Heikkilä, K, Silventoinen, K, Pietiläinen, K, Legry, V, Giedraitis, V, Goumidi, L, Syvänen, A, Strauch, K, Koenig, W, Lichtner, P, Herder, C, Palotie, A, Menni, C, Uitterlinden, A, Kuulasmaa, K, Havulinna, A, Moreno, L, Gonzalez Gross, M, Evans, A, Tregouet, D, Yarnell, J, Virtamo, J, Ferrières, J, Veronesi, G, Perola, M, Arveiler, D, Brambilla, P, Lind, L, Kaprio, J, Hofman, A, Stricker, B, van Duijn, C, Ikram, M, Franco, O, Cottel, D, Dallongeville, J, Hall, A, Jula, A, Tobin, M, Penninx, B, Peters, A, Gieger, C, Samani, N, Montgomery, G, Whitfield, J, Martin, N, Groop, L, Spector, T, Magnusson, P, Amouyel, P, Boomsma, D, Nilsson, P, Järvelin, M, Lyssenko, V, Metspalu, A, Strachan, D, Salomaa, V, Ripatti, S, Pedersen, N, Prokopenko, I, Mccarthy, M, Ingelsson, E, BRAMBILLA, PAOLO, and Ingelsson, E.
Abstract: Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 10-107) and stratified analyses (all P < 3.3 10-30). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ‡55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- And age-specific causal estimates on cardiovascular risk factors.
Published: 2015

14. Association of nutritional status as measured by the Mini-Nutritional Assessment Short Form with changes in mobility, institutionalization and death after hip fracture

Author: Nuotio, M, primary, Tuominen, P, additional, and Luukkaala, T, additional
Published: 2015
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15. P-441: Multiple medication use and renal insufficiency predict mortality in an older hip fracture population

Author: Pajulammi, H., primary, Pihlajamäki, H., additional, Luukkaala, T., additional, and Nuotio, M., additional
Published: 2015
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16. O-079: Nutritional status as measured by the Mini Nutritional Assessment Short Form as a predictor of hip fracture outcomes

Author: Nuotio, M., primary, Tuominen, P., additional, and Luukkaala, T., additional
Published: 2015
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17. The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

Author: Fall, M. (Magnus), Hägg, S. (Sara), Mägi, R. (Reedik), Ploner, A. (Alexander), Fischer, K. (Krista), Horikoshi, M. (Momoko), Sarin, A.-P., Thorleifsson, G. (Gudmar), Ladenvall, C. (Claes), Kals, M. (Mart), Kuningas, M. (Maris), Draisma, G. (Gerrit), Ried, J.S. (Janina), Zuydam, N.R. (Natalie) van, Huikari, V. (Ville), Mangino, M. (Massimo), Sonestedt, E. (Emily), Benyamin, B. (Beben), Nelson, C.P. (Christopher P.), Rivera, N.V. (Natalia), Kristiansson, K. (Kati), Shen, H.-y. (Huei-yi), Havulinna, A.S. (Aki), Dehghan, A. (Abbas), Donnelly, L.A. (Louise), Kaakinen, M. (Marika), Nuotio, M.-L. (Marja-Liisa), Robertson, N. (Neil), Bruijn, R.F.A.G. (Renée) de, Ikram, M.A. (Arfan), Amin, N. (Najaf), Balmforth, A.J. (Anthony), Braund, P.S. (Peter), Doney, A.S.F. (Alex), Döring, A. (Angela), Elliott, P. (Paul), Esko, T. (Tõnu), Franco, O.H. (Oscar), Gretarsdottir, S. (Solveig), Hartikainen, A.L., Heikkilä, K. (Kauko), Herzig, K.H., Holm, H. (Hilma), Hottenga, J.J. (Jouke Jan), Hyppönen, E. (Elina), Illig, T. (Thomas), Isaacs, A.J. (Aaron), Isomaa, B. (Bo), Karssen, L.C. (Lennart), Kettunen, J. (Johannes), Koenig, W. (Wolfgang), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Laitinen, J. (Jaana), Lindgren, C. (Cecilia), Lyssenko, V. (Valeriya), Läärä, E. (Esa), Rayner, N.W. (Nigel William), Männistö, S. (Satu), Pouta, A. (Anneli), Rathmann, W. (Wolfgang), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Savolainen, M.J. (Markku), Sijbrands, E.J.G. (Eric), Small, K.S. (Kerrin), Smit, J.H. (Jan), Steinthorsdottir, V. (Valgerdur), Syvanen, A.C., Taanila, A. (Anja), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Perola, M. (Markus), Evans, A. (Andrew), Ferrières, J. (Jean), Virtamo, J. (Jarmo), Kee, F. (F.), Tregouet, D.-A. (David-Alexandre), Arveiler, D. (Dominique), Amouyel, P. (Philippe), Ferrario, F. (Franco), Brambilla, P. (Paolo), Hall, A. (Anne), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Whitfield, J. (John), Jula, A. (Antti), Knekt, P., Oostra, B.A. (Ben), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Davey-Smith, G. (George), Kaprio, J. (Jaakko), Samani, N.J. (Nilesh), Gieger, C. (Christian), Peters, A. (Annette), Wichmann, H.E. (Heinz Erich), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Tuomi, T. (Tiinamaija), Power, C. (Christopher), Hammond, C.J. (Christopher), Spector, T.D. (Timothy), Lind, L. (Lars), Orho-Melander, M. (Marju), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Groop, L. (Leif), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Vartiainen, E. (Erkki), Hofman, A. (Albert), Ripatti, S. (Samuli), Metspalu, A. (Andres), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Pedersen, N.L. (Nancy), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Prokopenko, I. (Inga), Fall, M. (Magnus), Hägg, S. (Sara), Mägi, R. (Reedik), Ploner, A. (Alexander), Fischer, K. (Krista), Horikoshi, M. (Momoko), Sarin, A.-P., Thorleifsson, G. (Gudmar), Ladenvall, C. (Claes), Kals, M. (Mart), Kuningas, M. (Maris), Draisma, G. (Gerrit), Ried, J.S. (Janina), Zuydam, N.R. (Natalie) van, Huikari, V. (Ville), Mangino, M. (Massimo), Sonestedt, E. (Emily), Benyamin, B. (Beben), Nelson, C.P. (Christopher P.), Rivera, N.V. (Natalia), Kristiansson, K. (Kati), Shen, H.-y. (Huei-yi), Havulinna, A.S. (Aki), Dehghan, A. (Abbas), Donnelly, L.A. (Louise), Kaakinen, M. (Marika), Nuotio, M.-L. (Marja-Liisa), Robertson, N. (Neil), Bruijn, R.F.A.G. (Renée) de, Ikram, M.A. (Arfan), Amin, N. (Najaf), Balmforth, A.J. (Anthony), Braund, P.S. (Peter), Doney, A.S.F. (Alex), Döring, A. (Angela), Elliott, P. (Paul), Esko, T. (Tõnu), Franco, O.H. (Oscar), Gretarsdottir, S. (Solveig), Hartikainen, A.L., Heikkilä, K. (Kauko), Herzig, K.H., Holm, H. (Hilma), Hottenga, J.J. (Jouke Jan), Hyppönen, E. (Elina), Illig, T. (Thomas), Isaacs, A.J. (Aaron), Isomaa, B. (Bo), Karssen, L.C. (Lennart), Kettunen, J. (Johannes), Koenig, W. (Wolfgang), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Laitinen, J. (Jaana), Lindgren, C. (Cecilia), Lyssenko, V. (Valeriya), Läärä, E. (Esa), Rayner, N.W. (Nigel William), Männistö, S. (Satu), Pouta, A. (Anneli), Rathmann, W. (Wolfgang), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Savolainen, M.J. (Markku), Sijbrands, E.J.G. (Eric), Small, K.S. (Kerrin), Smit, J.H. (Jan), Steinthorsdottir, V. (Valgerdur), Syvanen, A.C., Taanila, A. (Anja), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Perola, M. (Markus), Evans, A. (Andrew), Ferrières, J. (Jean), Virtamo, J. (Jarmo), Kee, F. (F.), Tregouet, D.-A. (David-Alexandre), Arveiler, D. (Dominique), Amouyel, P. (Philippe), Ferrario, F. (Franco), Brambilla, P. (Paolo), Hall, A. (Anne), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Whitfield, J. (John), Jula, A. (Antti), Knekt, P., Oostra, B.A. (Ben), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Davey-Smith, G. (George), Kaprio, J. (Jaakko), Samani, N.J. (Nilesh), Gieger, C. (Christian), Peters, A. (Annette), Wichmann, H.E. (Heinz Erich), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Tuomi, T. (Tiinamaija), Power, C. (Christopher), Hammond, C.J. (Christopher), Spector, T.D. (Timothy), Lind, L. (Lars), Orho-Melander, M. (Marju), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Groop, L. (Leif), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Vartiainen, E. (Erkki), Hofman, A. (Albert), Ripatti, S. (Samuli), Metspalu, A. (Andres), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Pedersen, N.L. (Nancy), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), and Prokopenko, I. (Inga)
Abstract: Background:The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and Findings:We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses.Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05).
Published: 2013
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18. GWAS of 126,559 individuals identifies genetic variants associated with educational attainment

Author: Rietveld, C.A. (Niels), Medland, S.E. (Sarah), Derringer, J., Yang, J. (Joanna), Esko, T. (Tõnu), Martin, N.W. (Nicolas), Westra, H.J. (Harm-Jan), Shakhbazov, K. (Konstantin), Abdellaoui, A. (Abdel), Agrawal, A. (Arpana), Albrecht, E. (Eva), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Barnard, J. (John), Baumeister, S.E. (Sebastian), Benke, P.J. (Paul), Bielak, L.F. (Lawrence F.), Boatman, J.A. (Jeffrey), Boyle, P.A. (Patricia), Davies, G. (Gail), Leeuw, C. (Christiaan) de, Eklund, N. (Niina), Evans, D.S. (Daniel), Ferhmann, R. (Rudolf), Fischer, K. (Krista), Gieger, C. (Christian), Gjessing, H.K. (Håkon), Hägg, S. (Sara), Harris, J.R. (Jennifer), Hayward, C. (Caroline), Holzapfel, C. (Christina), Ibrahim-Verbaas, C.A. (Carla), Ingelsson, E. (Erik), Jacobsson, B. (Bo), Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kanoni, S. (Stavroula), Karjalainen, J. (Juha), Kolcic, I. (Ivana), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Lee, S.H. (Sang Hong), Lin, P. (Peng), Lind, P.A. (Penelope), Liu, Y. (YongMei), Lohman, K. (Kurt), Loitfelder, M. (Marisa), Mcmahon, G. (George), Marques-Vidal, P. (Pedro), Meirelles, O., Milani, L. (Lili), Myhre, R. (Ronny), Nuotio, M.-L. (Marja-Liisa), Oldmeadow, C. (Christopher), Petrovic, K. (Katja), Peyrot, W.J. (Wouter ), Polasek, O. (Ozren), Quaye, L. (Lydia), Reinmaa, E. (Eva), Rice, J.P. (John), Rizzi, T.S. (Thais), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Terracciano, A., Loos, M.J.H.M. (Matthijs) van der, Vitart, V. (Veronique), Völzke, H. (Henry), Wellmann, J. (Jürgen), Yu, L. (Lei), Zhao, W. (Wei), Allik, J., Attia, J. (John), Bandinelli, S. (Stefania), Bastardot, F. (Francois), Beauchamp, J.P. (Jonathan), Bennett, D.A. (David), Berger, K. (Klaus), Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Bültmann, U. (Ute), Campbell, H. (Harry), Chabris, C.F. (Christopher F.), Cherkas, L. (Lynn), Chung, M.K. (Mina), Cucca, F. (Francesco), Andrade, M. (Mariza) de, Jager, P.L. (Philip) de, Neve, J.E. (Jan-Emmanuel) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Dimitriou, M. (Maria), Eiríksdóttir, G. (Guoný), Elderson, M.F. (Martin), Eriksson, J.G. (Johan), Evans, D.M. (David), Faul, J.D. (Jessica), Ferrucci, L. (Luigi), Garcia, M. (Melissa), Grönberg, H. (Henrik), Guonason, V. (Vilmundur), Hall, P. (Per), Harris, J.M. (Juliette), Harris, T.B. (Tamara), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hoffmann, W. (Wolfgang), Holle, R. (Rolf), Holliday, E.G. (Elizabeth), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kirkpatrick, R.M. (Robert), Kowgier, M. (Matthew), Latvala, A. (Antti), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Li, J. (Jingmei), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Mäkinen, T. (Tuukka), Masala, G. (Giovanna), McGue, M. (Matt), Metspalu, A. (Andres), Mielck, A. (Andreas), Miller, M. (Michael), Montgomery, G.W. (Grant), Mukherjee, S. (Sutapa), Nyholt, D.R. (Dale), Oostra, B.A. (Ben), Palmer, C. (Cameron), Palotie, A. (Aarno), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peyser, P.A. (Patricia A.), Preisig, M. (Martin), Räikkönen, K. (Katri), Raitakari, O. (Olli), Realo, A. (Anu), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sarin, A.-P., Schlessinger, D., Scott, R.J. (Rodney), Snieder, H. (Harold), St Pourcain, B. (Beate), Starr, J.M. (John), Sul, J.H. (Jae Hoon), Surakka, I. (Ida), Svento, R. (Rauli), Teumer, A. (Alexander), Tiemeier, H.W. (Henning), Rooij, F.J.A. (Frank) van, Wagoner, D.R. (David) van, Vartiainen, E. (Erkki), Viikari, J. (Jorma), Vollenweider, P. (Peter), Vonk, J.M. (Judith), Waeber, G. (Gérard), Weir, D.R. (David), Wichmann, H.E. (Heinz Erich), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Conley, D. (Dalton), Davey-Smith, G. (George), Franke, L. (Lude), Groenen, P.J.F. (Patrick), Hofman, A. (Albert), Johannesson, M. (Magnus), Kardia, S.L.R. (Sharon), Krueger, R.F., Laibson, D. (David), Martin, N.G. (Nicholas), Meyer, M.N. (Michelle), Posthuma, D. (Danielle), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), Koellinger, Ph.D. (Philipp), Rietveld, C.A. (Niels), Medland, S.E. (Sarah), Derringer, J., Yang, J. (Joanna), Esko, T. (Tõnu), Martin, N.W. (Nicolas), Westra, H.J. (Harm-Jan), Shakhbazov, K. (Konstantin), Abdellaoui, A. (Abdel), Agrawal, A. (Arpana), Albrecht, E. (Eva), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Barnard, J. (John), Baumeister, S.E. (Sebastian), Benke, P.J. (Paul), Bielak, L.F. (Lawrence F.), Boatman, J.A. (Jeffrey), Boyle, P.A. (Patricia), Davies, G. (Gail), Leeuw, C. (Christiaan) de, Eklund, N. (Niina), Evans, D.S. (Daniel), Ferhmann, R. (Rudolf), Fischer, K. (Krista), Gieger, C. (Christian), Gjessing, H.K. (Håkon), Hägg, S. (Sara), Harris, J.R. (Jennifer), Hayward, C. (Caroline), Holzapfel, C. (Christina), Ibrahim-Verbaas, C.A. (Carla), Ingelsson, E. (Erik), Jacobsson, B. (Bo), Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kanoni, S. (Stavroula), Karjalainen, J. (Juha), Kolcic, I. (Ivana), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Lee, S.H. (Sang Hong), Lin, P. (Peng), Lind, P.A. (Penelope), Liu, Y. (YongMei), Lohman, K. (Kurt), Loitfelder, M. (Marisa), Mcmahon, G. (George), Marques-Vidal, P. (Pedro), Meirelles, O., Milani, L. (Lili), Myhre, R. (Ronny), Nuotio, M.-L. (Marja-Liisa), Oldmeadow, C. (Christopher), Petrovic, K. (Katja), Peyrot, W.J. (Wouter ), Polasek, O. (Ozren), Quaye, L. (Lydia), Reinmaa, E. (Eva), Rice, J.P. (John), Rizzi, T.S. (Thais), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Terracciano, A., Loos, M.J.H.M. (Matthijs) van der, Vitart, V. (Veronique), Völzke, H. (Henry), Wellmann, J. (Jürgen), Yu, L. (Lei), Zhao, W. (Wei), Allik, J., Attia, J. (John), Bandinelli, S. (Stefania), Bastardot, F. (Francois), Beauchamp, J.P. (Jonathan), Bennett, D.A. (David), Berger, K. (Klaus), Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Bültmann, U. (Ute), Campbell, H. (Harry), Chabris, C.F. (Christopher F.), Cherkas, L. (Lynn), Chung, M.K. (Mina), Cucca, F. (Francesco), Andrade, M. (Mariza) de, Jager, P.L. (Philip) de, Neve, J.E. (Jan-Emmanuel) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Dimitriou, M. (Maria), Eiríksdóttir, G. (Guoný), Elderson, M.F. (Martin), Eriksson, J.G. (Johan), Evans, D.M. (David), Faul, J.D. (Jessica), Ferrucci, L. (Luigi), Garcia, M. (Melissa), Grönberg, H. (Henrik), Guonason, V. (Vilmundur), Hall, P. (Per), Harris, J.M. (Juliette), Harris, T.B. (Tamara), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hoffmann, W. (Wolfgang), Holle, R. (Rolf), Holliday, E.G. (Elizabeth), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kirkpatrick, R.M. (Robert), Kowgier, M. (Matthew), Latvala, A. (Antti), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Li, J. (Jingmei), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Mäkinen, T. (Tuukka), Masala, G. (Giovanna), McGue, M. (Matt), Metspalu, A. (Andres), Mielck, A. (Andreas), Miller, M. (Michael), Montgomery, G.W. (Grant), Mukherjee, S. (Sutapa), Nyholt, D.R. (Dale), Oostra, B.A. (Ben), Palmer, C. (Cameron), Palotie, A. (Aarno), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peyser, P.A. (Patricia A.), Preisig, M. (Martin), Räikkönen, K. (Katri), Raitakari, O. (Olli), Realo, A. (Anu), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sarin, A.-P., Schlessinger, D., Scott, R.J. (Rodney), Snieder, H. (Harold), St Pourcain, B. (Beate), Starr, J.M. (John), Sul, J.H. (Jae Hoon), Surakka, I. (Ida), Svento, R. (Rauli), Teumer, A. (Alexander), Tiemeier, H.W. (Henning), Rooij, F.J.A. (Frank) van, Wagoner, D.R. (David) van, Vartiainen, E. (Erkki), Viikari, J. (Jorma), Vollenweider, P. (Peter), Vonk, J.M. (Judith), Waeber, G. (Gérard), Weir, D.R. (David), Wichmann, H.E. (Heinz Erich), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Conley, D. (Dalton), Davey-Smith, G. (George), Franke, L. (Lude), Groenen, P.J.F. (Patrick), Hofman, A. (Albert), Johannesson, M. (Magnus), Kardia, S.L.R. (Sharon), Krueger, R.F., Laibson, D. (David), Martin, N.G. (Nicholas), Meyer, M.N. (Michelle), Posthuma, D. (Danielle), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), and Koellinger, Ph.D. (Philipp)
Published: 2013
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19. The role of adiposity in cardiometabolic traits: a mendelian randomization analysis

Author: Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, Prokopenko, I., Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, and Prokopenko, I.
Abstract: Background:The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and Findings:We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses.Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (
Published: 2013

20. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals

Author: Dastani, Z. (Zari), Hivert, M.-F. (Marie-France), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Yuan, X. (Xin), Scott, R.A. (Robert), Hennemann, P. (Peter), Heid, I.M. (Iris), Kizer, J.R. (Jorge), Lyytikäinen, L.-P. (Leo-Pekka), Fuchsberger, C. (Christian), Tanaka, T. (Toshiko), Morris, A.P. (Andrew), Small, K.S. (Kerrin), Isaacs, A.J. (Aaron), Beekman, M. (Marian), Coassin, S. (Stefan), Lohman, K. (Kurt), Qi, L. (Lu), Kanoni, S. (Stavroula), Pankow, J.S. (James), Uh, H.-W. (Hae-Won), Wu, Y. (Ying), Bidulescu, A. (Aurelian), Rasmussen-Torvik, L.J. (Laura), Greenwood, C.M.T. (Celia), Ladouceur, M. (Martin), Grimsby, J.L. (Jonna), Manning, A.K. (Alisa), Liu, C.-T. (Ching-Ti), Kooner, J.S. (Jaspal), Mooser, V. (Vincent), Vollenweider, P. (Peter), Kapur, K. (Karen), Chambers, J. (John), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Frants, R.R. (Rune), Willems van Dijk, J.A.P. (Ko), Oostra, B.A. (Ben), Willems, S.M. (Sara), Lamina, C. (Claudia), Winkler, T.W. (Thomas), Psaty, B.M. (Bruce), Tracy, R.P. (Russell), Brody, J.A. (Jennifer A.), Chen, I. (Ida), Viikari, J. (Jorma), Kähönen, M. (Mika), Pramstaller, P.P. (Peter Paul), Evans, D.M. (David), St Pourcain, B. (Beate), Sattar, N. (Naveed), Wood, A.R. (Andrew), Bandinelli, S. (Stefania), Carlson, O.D. (Olga), Egan, J.M. (Josephine), Böhringer, S. (Stefan), Heemst, D. (Diana) van, Kedenko, L. (Lyudmyla), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Loo, B.-M. (Britt-Marie), Harris, T.B. (Tamara), Garcia, M. (Melissa), Kanaya, A. (Alka), Haun, M. (Margot), Klopp, N. (Norman), Wichmann, H.E. (Erich), Deloukas, P. (Panagiotis), Katsareli, E. (Efi), Couper, D.J. (David), Duncan, B.B. (Bruce), Kloppenburg, M. (Margreet), Adair, L.S. (Linda), Borja, J.B. (Judith), Wilson, J.G. (James), Musani, S. (Solomon), Guo, X. (Xiuqing), Johnson, T. (Toby), Semple, R.K. (Robert), Teslovich, T.M. (Tanya), Allison, M.A. (Matthew), Redline, S. (Susan), Buxbaum, S.G. (Sarah), Mohlke, K.L. (Karen), Meulenbelt, I. (Ingrid), Ballantyne, C. (Christie), Dedoussis, G.V. (George), Hu, F.B. (Frank), Liu, Y. (YongMei), Paulweber, B. (Bernhard), Spector, T.D. (Timothy), Slagboom, P.E. (Eline), Ferrucci, L. (Luigi), Jula, A. (Antti), Perola, M. (Markus), Raitakari, O.T. (Olli T.), Florez, J.C. (Jose), Salomaa, V. (Veikko), Eriksson, J.G. (Johan), Frayling, T.M. (Timothy), Hicks, A.A. (Andrew), Lehtimäki, T. (Terho), Smith, G.D. (George Davey), Siscovick, D.S. (David), Kronenberg, F. (Florian), Duijn, C.M. (Cornelia) van, Loos, R.J.F. (Ruth), Waterworth, D.M. (Dawn), Meigs, J.B. (James), Dupuis, J. (Josée), Richards, J.B. (Brent), Dastani, Z. (Zari), Hivert, M.-F. (Marie-France), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Yuan, X. (Xin), Scott, R.A. (Robert), Hennemann, P. (Peter), Heid, I.M. (Iris), Kizer, J.R. (Jorge), Lyytikäinen, L.-P. (Leo-Pekka), Fuchsberger, C. (Christian), Tanaka, T. (Toshiko), Morris, A.P. (Andrew), Small, K.S. (Kerrin), Isaacs, A.J. (Aaron), Beekman, M. (Marian), Coassin, S. (Stefan), Lohman, K. (Kurt), Qi, L. (Lu), Kanoni, S. (Stavroula), Pankow, J.S. (James), Uh, H.-W. (Hae-Won), Wu, Y. (Ying), Bidulescu, A. (Aurelian), Rasmussen-Torvik, L.J. (Laura), Greenwood, C.M.T. (Celia), Ladouceur, M. (Martin), Grimsby, J.L. (Jonna), Manning, A.K. (Alisa), Liu, C.-T. (Ching-Ti), Kooner, J.S. (Jaspal), Mooser, V. (Vincent), Vollenweider, P. (Peter), Kapur, K. (Karen), Chambers, J. (John), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Frants, R.R. (Rune), Willems van Dijk, J.A.P. (Ko), Oostra, B.A. (Ben), Willems, S.M. (Sara), Lamina, C. (Claudia), Winkler, T.W. (Thomas), Psaty, B.M. (Bruce), Tracy, R.P. (Russell), Brody, J.A. (Jennifer A.), Chen, I. (Ida), Viikari, J. (Jorma), Kähönen, M. (Mika), Pramstaller, P.P. (Peter Paul), Evans, D.M. (David), St Pourcain, B. (Beate), Sattar, N. (Naveed), Wood, A.R. (Andrew), Bandinelli, S. (Stefania), Carlson, O.D. (Olga), Egan, J.M. (Josephine), Böhringer, S. (Stefan), Heemst, D. (Diana) van, Kedenko, L. (Lyudmyla), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Loo, B.-M. (Britt-Marie), Harris, T.B. (Tamara), Garcia, M. (Melissa), Kanaya, A. (Alka), Haun, M. (Margot), Klopp, N. (Norman), Wichmann, H.E. (Erich), Deloukas, P. (Panagiotis), Katsareli, E. (Efi), Couper, D.J. (David), Duncan, B.B. (Bruce), Kloppenburg, M. (Margreet), Adair, L.S. (Linda), Borja, J.B. (Judith), Wilson, J.G. (James), Musani, S. (Solomon), Guo, X. (Xiuqing), Johnson, T. (Toby), Semple, R.K. (Robert), Teslovich, T.M. (Tanya), Allison, M.A. (Matthew), Redline, S. (Susan), Buxbaum, S.G. (Sarah), Mohlke, K.L. (Karen), Meulenbelt, I. (Ingrid), Ballantyne, C. (Christie), Dedoussis, G.V. (George), Hu, F.B. (Frank), Liu, Y. (YongMei), Paulweber, B. (Bernhard), Spector, T.D. (Timothy), Slagboom, P.E. (Eline), Ferrucci, L. (Luigi), Jula, A. (Antti), Perola, M. (Markus), Raitakari, O.T. (Olli T.), Florez, J.C. (Jose), Salomaa, V. (Veikko), Eriksson, J.G. (Johan), Frayling, T.M. (Timothy), Hicks, A.A. (Andrew), Lehtimäki, T. (Terho), Smith, G.D. (George Davey), Siscovick, D.S. (David), Kronenberg, F. (Florian), Duijn, C.M. (Cornelia) van, Loos, R.J.F. (Ruth), Waterworth, D.M. (Dawn), Meigs, J.B. (James), Dupuis, J. (Josée), and Richards, J.B. (Brent)
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8- 1.2 ×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- choles
Published: 2012
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21. Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

Author: Dastani, Z, Hivert, M-F, Timpson, N, Perry, JRB, Yuan, X, Scott, RA, Henneman, P, Heid, IM, Kizer, JR, Lyytikainen, L-P, Fuchsberger, C, Tanaka, T, Morris, AP, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, JS, Uh, H-W, Wu, Y, Bidulescu, A, Rasmussen-Torvik, LJ, Greenwood, CMT, Ladouceur, M, Grimsby, J, Manning, AK, Liu, C-T, Kooner, J, Mooser, VE, Vollenweider, P, Kapur, KA, Chambers, J, Wareham, NJ, Langenberg, C, Frants, R, Willems-vanDijk, K, Oostra, BA, Willems, SM, Lamina, C, Winkler, TW, Psaty, BM, Tracy, RP, Brody, J, Chen, I, Viikari, J, Kahonen, M, Pramstaller, PP, Evans, DM, St Pourcain, B, Sattar, N, Wood, AR, Bandinelli, S, Carlson, OD, Egan, JM, Bohringer, S, van Heemst, D, Kedenko, L, Kristiansson, K, Nuotio, M-L, Loo, B-M, Harris, T, Garcia, M, Kanaya, A, Haun, M, Klopp, N, Wichmann, H-E, Deloukas, P, Katsareli, E, Couper, DJ, Duncan, BB, Kloppenburg, M, Adair, LS, Borja, JB, Wilson, JG, Musani, S, Guo, X, Johnson, T, Semple, R, Teslovich, TM, Allison, MA, Redline, S, Buxbaum, SG, Mohlke, KL, Meulenbelt, I, Ballantyne, CM, Dedoussis, GV, Hu, FB, Liu, Y, Paulweber, B, Spector, TD, Slagboom, PE, Ferrucci, L, Jula, A, Perola, M, Raitakari, O, Florez, JC, Salomaa, V, Eriksson, JG, Frayling, TM, Hicks, AA, Lehtimaki, T, Smith, GD, Siscovick, DS, Kronenberg, F, van Duijn, C, Loos, RJF, Waterworth, DM, Meigs, JB, Dupuis, J, Richards, JB, Dastani, Z, Hivert, M-F, Timpson, N, Perry, JRB, Yuan, X, Scott, RA, Henneman, P, Heid, IM, Kizer, JR, Lyytikainen, L-P, Fuchsberger, C, Tanaka, T, Morris, AP, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, JS, Uh, H-W, Wu, Y, Bidulescu, A, Rasmussen-Torvik, LJ, Greenwood, CMT, Ladouceur, M, Grimsby, J, Manning, AK, Liu, C-T, Kooner, J, Mooser, VE, Vollenweider, P, Kapur, KA, Chambers, J, Wareham, NJ, Langenberg, C, Frants, R, Willems-vanDijk, K, Oostra, BA, Willems, SM, Lamina, C, Winkler, TW, Psaty, BM, Tracy, RP, Brody, J, Chen, I, Viikari, J, Kahonen, M, Pramstaller, PP, Evans, DM, St Pourcain, B, Sattar, N, Wood, AR, Bandinelli, S, Carlson, OD, Egan, JM, Bohringer, S, van Heemst, D, Kedenko, L, Kristiansson, K, Nuotio, M-L, Loo, B-M, Harris, T, Garcia, M, Kanaya, A, Haun, M, Klopp, N, Wichmann, H-E, Deloukas, P, Katsareli, E, Couper, DJ, Duncan, BB, Kloppenburg, M, Adair, LS, Borja, JB, Wilson, JG, Musani, S, Guo, X, Johnson, T, Semple, R, Teslovich, TM, Allison, MA, Redline, S, Buxbaum, SG, Mohlke, KL, Meulenbelt, I, Ballantyne, CM, Dedoussis, GV, Hu, FB, Liu, Y, Paulweber, B, Spector, TD, Slagboom, PE, Ferrucci, L, Jula, A, Perola, M, Raitakari, O, Florez, JC, Salomaa, V, Eriksson, JG, Frayling, TM, Hicks, AA, Lehtimaki, T, Smith, GD, Siscovick, DS, Kronenberg, F, van Duijn, C, Loos, RJF, Waterworth, DM, Meigs, JB, Dupuis, J, and Richards, JB
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
Published: 2012

22. Prospects of geriatric medicine in acute specialized hospitals in Finland

Author: Nuotio, M., primary, Salonoja, M., additional, and Seppänen, M.L., additional
Published: 2013
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23. Factors associated with outcomes of mobility and living arrangements in a comprehensive geriatric assessment after hip fracture

Author: Nuotio, M., primary and Luukkaala, T., additional
Published: 2013
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24. Review of potentially harmful medications in memory impaired outpatients with polypharmacy

Author: Nuotio, M., primary, Juonoja, T., additional, Haanpää, K., additional, Lampi, K., additional, and Tiippana, P., additional
Published: 2012
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25. Urinary incontinence–an overview from Finland

Author: Nuotio, M., primary
Published: 2011
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26. Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

Author: Seppo Koskinen, Christian Herder, Daniel I. Chasman, Andrew R. Wood, Jonna L. Grimsby, J.F. Wilson, Day Inm., Massimo Mangino, Gonneke Willemsen, Robert W. Mahley, Cristian Pattaro, Nicole L. Glazer, T.B. Harris, Irene Pichler, M S Sandhu, D. van Heemst, Christine Proença, Martha Ganser, Robert A. Hegele, Richa Saxena, Eleftheria Zeggini, Markku Laakso, Peter Kraft, Judith B. Borja, Karen L. Mohlke, J B Richards, de Geus Ejc., Robert Sladek, Cristen J. Willer, Samy Hadjadj, S.M. Boekholdt, Gina M. Peloso, Kijoung Song, Sutapa Mukherjee, Gudmar Thorleifsson, Winston Hide, Mark I. McCarthy, Ruth E. Pakyz, Marian Beekman, Ayellet V. Segrè, Inga Prokopenko, Ping An, George Dedoussis, Danielle Posthuma, Jeanette Erdmann, Simon J. Griffin, Nilesh J. Samani, Inke R. König, Frank B. Hu, Lokki M-L., David M. Evans, Xiaohui Li, Valgerdur Steinthorsdottir, Aimo Ruokonen, A Pouta, Kerrin S. Small, Cecilia M. Lindgren, O Le Bacquer, Xijing Han, Florian Kronenberg, E Katsareli, Christian Dina, S. Gabriel, Jochen Spranger, James S. Pankow, M. Kloppenburg, Penninx Bwjh., Torben Hansen, Josh Smith, Jennie Hui, Gordon H. Williams, Mark Seielstad, Ingrid B. Borecki, Weihua Zhang, Peter P. Pramstaller, Stephen J. Sharp, Neil R. Robertson, Zee Ryl., Mike Sampson, Angela Silveira, C.M. van Duijn, Anders Hamsten, Peter Shrader, Denis Rybin, Chen Y-Di., Gunnar Sigurdsson, Michael Stumvoll, Russel Tracy, Mark O. Goodarzi, Göran Hallmans, Michael R. Erdos, Valeriya Lyssenko, Juha Saharinen, Sven Bergmann, Jeffrey R. O'Connell, Debbie A Lawlor, Thomas Meitinger, Yvonne Böttcher, Jérôme Delplanque, Sarah G. Buxbaum, Silvia Naitza, Shah Ebrahim, Graham A. Hitman, Angelo Scuteri, Aroon D. Hingorani, Heribert Schunkert, François Pattou, Claudia Lamina, A L Elliott, Sekar Kathiresan, Dawn M. Waterworth, Jennifer A. Brody, Thomas Quertermous, Leena Peltonen, Josephine M. Egan, Daniel J. Rader, J F Peden, Yarnell Jwg., Daniel S. Pearson, Pfeiffer Afh., P S Chines, N Vogelzangs, Susan Redline, Alka M. Kanaya, T B Harris, J. V. van Vliet-Ostaptchouk, Ghislain Rocheleau, Rune R. Frants, Olga D. Carlson, James G. Wilson, Melissa Garcia, Ong Rt-H., Mark J. Caulfield, Tanya M. Teslovich, Loo B-M., Beatrice Knight, Andreas Ziegler, Claudia Langenberg, Yoon Shin Cho, Paul M. Ridker, Mark J. Rieder, Praveen Sethupathy, Bert Bravenboer, J. Viikari, Matt Neville, Ioannis M. Stylianou, Andrew Walley, Jarvelin M-R., Jarred B. McAteer, Ronald M. Krauss, Augustine Kong, Oluf Pedersen, Mark J. Daly, Andrew P. Morris, Anna F. Dominiczak, Stéphane Cauchi, Michael Boehnke, Christopher J. O'Donnell, Barbara Thorand, Peter M. Nilsson, Aaron Isaacs, Deborah A. Nickerson, Roza Blagieva, Mary F. Feitosa, Nicholas J. Wareham, Robert Roberts, J S Kooner, K W van Dijk, Tiinamaija Tuomi, Paul Scheet, Lynda M. Rose, Albert V. Smith, Rafn Benediktsson, Chiara Sabatti, Candace Guiducci, Lee M. Kaplan, Aki S. Havulinna, Toby Johnson, Samuli Ripatti, Erik Ingelsson, Mario A. Morken, Carl G. P. Platou, Anke Tönjes, Qi Sun, Narisu Narisu, S J Bumpstead, Jose M. Ordovas, Alan B. Feranil, L Groop, P Chines, Sara M. Willems, Perry Jrb., Matthew A. Allison, Jan Scott, Cécile Lecoeur, Kastelein Jjp., Herman A. Taylor, Anyuan Cao, Christopher J. Groves, Lincoln D. Stein, Laura J. Scott, John Beilby, Kristin G. Ardlie, Christopher S. Franklin, Yoav Ben-Shlomo, B M Shields, N J Timpson, Marco Orrù, Amélie Bonnefond, Kiran Musunuru, Murielle Bochud, Udo Seedorf, Yongmei Liu, Guillaume Lettre, Lee J-Y., Alan R. Shuldiner, Ryan P. Welch, David J. Hunter, John Whitfield, Klaus Strassburger, Khaw K-T., Hartikainen A-L., Gunnar Sigurðsson, Lu Qi, Richard N. Bergman, G M Lathrop, Sigrid W. Fouchier, T van Herpt, David S. Siscovick, Igor Rudan, Richard M. Watanabe, Themistocles L. Assimes, Nicholas G. Martin, Ozren Polasek, Dhiraj Varma, K Kim, Oliver Hofmann, Nicholas D. Hastie, S Bumpstead, Jose C. Florez, Fernando Rivadeneira, Katharine R. Owen, Braxton D. Mitchell, Alisa K. Manning, Abbas Dehghan, Bruce Bartholow Duncan, Cisca Wijmenga, Timo T. Valle, Jaakko Kaprio, Mika Kivimäki, B Shields, Laila Simpson, Tim D. Spector, Paul W. Franks, Guangju Zhai, María Teresa Martínez-Larrad, Janssens Acjw., Kim L. Ward, Inês Barroso, Xiuqing Guo, Rosa Maria Roccasecca, Zari Dastani, Reijo Laaksonen, Wilmar Igl, Vincent Mooser, Niels Grarup, Cornelia Huth, Christian Gieger, Fabio Marroni, Jaakko Tuomilehto, Doney Asf., Andrew C. Edmondson, Christian Fuchsberger, Meena Kumari, David M. Nathan, Reedik Mägi, Solomon K. Musani, U de Faire, Knut Borch-Johnsen, Masahiro Koseki, Giuseppe Paolisso, Norman Klopp, Caroline S. Fox, Nelson B. Freimer, Mika Kähönen, Peter Henneman, Diana Zelenika, K Willems-Vandijk, Steven A. McCarroll, Paul Elliott, Wichmann H-E., J. C. Bis, Nita G. Forouhi, Antti Jula, Witteman Jcm., Fredrik Karpe, Joseph Hung, Antje Fischer-Rosinsky, Eric J. Brunner, Elena Gonzalez, Soumya Raychaudhuri, Jian'an Luan, Josée Dupuis, Joshua C. Randall, Taesung Park, Francis S. Collins, Lori L. Bonnycastle, Andrew A. Hicks, Peter Kovacs, Thomas Illig, Maja Barbalić, David Couper, Jaspal S. Kooner, Damien C. Croteau-Chonka, Gavin Lucas, P J Wagner, Young-Jin Kim, Yurii S. Aulchenko, Aurelian Bidulescu, Ingrid Meulenbelt, Pilar Galan, Iris M. Heid, Michael N. Weedon, Serena Sanna, Sarah H. Wild, Hivert M-F., Patricia B. Munroe, Johan G. Eriksson, Teresa Ferreira, Robert A. Scott, A. Sandbaek, Kenneth Rice, Veronique Vitart, Xin Yuan, Leslie A. Lange, Hilma Holm, Jorge R. Kizer, Timothy M. Frayling, Marika Kaakinen, Liu C-T., Petersen A-K., Peter Schwarz, G B Walters, Palmer Cna., Jean Tichet, Bernhard Paulweber, Ying Wu, Alyson Hall, Christopher T. Johansen, David Masson, Martin Ladouceur, Christie M. Ballantyne, Tai E-S., Robert Luben, Guillaume Charpentier, Angela Döring, Philip J. Barter, Ruth McPherson, Benjamin F. Voight, Wolfgang Rathmann, Mark Walker, Markus Perola, M. A. Province, Veikko Salomaa, James B. Meigs, George Davey Smith, Robert Clarke, Gerard Waeber, Stefania Bandinelli, Sally L. Ricketts, Kaisa Silander, Loos Rjf., Amanda J. Bennett, John C. Chambers, Marilyn C. Cornelis, L A Cupples, Andrew T. Hattersley, M Sandhu, Marju Orho-Melander, C M van Duijn, Olli T. Raitakari, David Meyre, Ida Surakka, Jouke-Jan Hottenga, Uh H-W., Kari Stefansson, David Melzer, P E Slagboom, Kristian Midthjell, Robert K. Semple, James P. Pirruccello, Aloysius G Lieverse, Åsa Johansson, Michael Roden, Felicity Payne, Eric J.G. Sijbrands, N P Burtt, David R. Hillman, Michael Marmot, Todd Green, Eric E. Schadt, Sijbrands Ejg., Tien Yin Wong, Coin Ljm., K B Boström, Olov Rolandsson, A D Morris, David Altshuler, Harald Grallert, L C Groop, Alan F. Wright, Karen Kapur, Xueling Sim, Philippe Froguel, K O Kyvik, T. Lauritzen, Linda S. Adair, Yavuz Ariyurek, Talin Haritunians, Toshiko Tanaka, Albert Hofman, MariaGrazia Franzosi, Nicholas L. Smith, Laura Crisponi, Andrew B. Singleton, A Uitterlinden, Bo Isomaa, Y A Kesaniemi, Anne U. Jackson, Christa Meisinger, Holly E. Syddall, Dorret I. Boomsma, Harry Campbell, Gonçalo R. Abecasis, Lyudmyla Kedenko, Christine Cavalcanti-Proença, G Crawford, Scott M. Grundy, Johnson Prv., Nuotio M-L., I Chen, J.H. Smit, Anuj Goel, M Li, David P. Strachan, Kenechi Ejebe, Beverley Balkau, Neelam Hassanali, Kristian Hveem, Pierre Meneton, R. Gwilliam, A J Swift, Caroline Hayward, J. Graessler, Carina Zabena, B. St Pourcain, Michel Marre, Margot Haun, Lyytikäinen L-P., Ben A. Oostra, Stefan Coassin, M. van Hoek, Nigel W. Rayner, John R. Thompson, Kurt Lohman, Ulla Sovio, Unnur Thorsteinsdottir, Naveed Sattar, Lyle J. Palmer, Ulf Gyllensten, A Elliott, Muredach P. Reilly, A Swift, Luigi Ferrucci, Syvänen A-C., Simon C. Potter, T.W. van Haeften, G Wu, Stefan Böhringer, Grant W. Montgomery, Edward G. Lakatta, Serkalem Demissie, Alex S. F. Doney, Najaf Amin, Lenore J. Launer, Hugh Watkins, Johanna Kuusisto, Lars Lind, Stefan R. Bornstein, Laura J. Rasmussen-Torvik, Terho Lehtimäki, Guillaume Paré, Sophie Visvikis-Siest, S C Heath, David Schlessinger, Juha Sinisalo, Kao Whl., Mark E. Cooper, Kati Kristiansson, Thomas W. Winkler, Thomas Sparsø, Laura J. McCulloch, Taina K. Lajunen, Alex N. Parker, Nabila Bouatia-Naji, Markku S. Nieminen, Peter Vollenweider, Wendy L. McArdle, G K Hovingh, Thomas A. Buchanan, Avan Aihie Sayer, M C Zillikens, Jing Hua Zhao, Naomi Hammond, Vilmundur Gudnason, Björn Zethelius, Panos Deloukas, Jacqueline C. M. Witteman, Eric Boerwinkle, Manuel Serrano-Ríos, Anna L. Gloyn, Katherine S. Elliott, A C Fedson, Torben Jørgensen, Nicole Soranzo, Heather M. Stringham, Bruce M. Psaty, A G Uitterlinden, Stavroula Kanoni, Christian Hengstenberg, Yun Li, Olle Melander, Alan R. Tall, Manuela Uda, Magnusson Pke., Christopher W. Kuzawa, V Mooser, R. M. van Dam, Jerome I. Rotter, Greenwood Cmt., Cyrus Cooper, Pau Navarro, Min Jin Go, Nancy L. Pedersen, Serge Hercberg, Bernhard O. Boehm, Eleanor Wheeler, Epidemiology, Medical Microbiology & Infectious Diseases, Clinical Genetics, Dastani, Z, Hivert, Mf, Timpson, N, Perry, Jr, Yuan, X, Scott, Ra, Henneman, P, Heid, Im, Kizer, Jr, Lyytikäinen, Lp, Fuchsberger, C, Tanaka, T, Morris, Ap, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, J, Uh, Hw, Wu, Y, Bidulescu, A, Rasmussen Torvik, Lj, Greenwood, Cm, Ladouceur, M, Grimsby, J, Manning, Ak, Liu, Ct, Kooner, J, Mooser, Ve, Vollenweider, P, Kapur, Ka, Chambers, J, Wareham, Nj, Langenberg, C, Frants, R, Willems Vandijk, K, Oostra, Ba, Willems, Sm, Lamina, C, Winkler, Tw, Psaty, Bm, Tracy, Rp, Brody, J, Chen, I, Viikari, J, Kähönen, M, Pramstaller, Pp, Evans, Dm, St Pourcain, B, Sattar, N, Wood, Ar, Bandinelli, S, Carlson, Od, Egan, Jm, Böhringer, S, van Heemst, D, Kedenko, L, Kristiansson, K, Nuotio, Ml, Loo, Bm, Harris, T, Garcia, M, Kanaya, A, Haun, M, Klopp, N, Wichmann, He, Deloukas, P, Katsareli, E, Couper, Dj, Duncan, Bb, Kloppenburg, M, Adair, L, Borja, Jb, DIAGRAM+, Consortium, Magic, Consortium, Glgc, Investigator, Muther, Consortium, Wilson, Jg, Musani, S, Guo, X, Johnson, T, Semple, R, Teslovich, Tm, Allison, Ma, Redline, S, Buxbaum, Sg, Mohlke, Kl, Meulenbelt, I, Ballantyne, Cm, Dedoussis, Gv, Hu, Fb, Liu, Y, Paulweber, B, Spector, Td, Slagboom, Pe, Ferrucci, L, Jula, A, Perola, M, Raitakari, O, Florez, Jc, Salomaa, V, Eriksson, Jg, Frayling, Tm, Hicks, Aa, Lehtimäki, T, Smith, Gd, Siscovick, D, Kronenberg, F, van Duijn, C, Loos, Rj, Waterworth, Dm, Meigs, Jb, Dupuis, J, Richards, Jb, Voight, Bf, Scott, Lj, Steinthorsdottir, V, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Morris, Ad, Palmer, Cn, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Pedersen, O, Barroso, I, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Elliott, P, Rybin, D, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Lajunen, T, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sigurðsson, G, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Diagram, Consortium, Giant, Consortium, Global B., Pgen Consortium, Borecki, Ib, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Serrano Ríos, M, Lind, L, Palmer, Lj, Hu FB, 1st, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Procardis, Consortium, Buchanan, Ta, Valle, Tt, Rotter, Ji, Penninx, Bw, Boomsma, Di, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Peltonen, L, Mooser, V, Magic, Investigator, Glgc, Consortium, Musunuru, K, Smith, Av, Edmondson, Ac, Stylianou, Im, Koseki, M, Pirruccello, Jp, Chasman, Di, Johansen, Ct, Fouchier, Sw, Peloso, Gm, Barbalic, M, Ricketts, Sl, Bis, Jc, Feitosa, Mf, Orho Melander, M, Melander, O, Li, X, Cho, Y, Go, Mj, Kim, Yj, Lee, Jy, Park, T, Kim, K, Sim, X, Ong, Rt, Croteau Chonka, Dc, Lange, La, Smith, Jd, Ziegler, A, Zhang, W, Zee, Ry, Whitfield, Jb, Thompson, Jr, Surakka, I, Smit, Jh, Sinisalo, J, Scott, J, Saharinen, J, Sabatti, C, Rose, Lm, Roberts, R, Rieder, M, Parker, An, Pare, G, O'Donnell, Cj, Nieminen, M, Nickerson, Da, Montgomery, Gw, Mcardle, W, Masson, D, Martin, Ng, Marroni, F, Lucas, G, Luben, R, Lokki, Ml, Lettre, G, Launer, Lj, Lakatta, Eg, Laaksonen, R, König, Ir, Khaw, Kt, Kaplan, Lm, Johansson, Å, Janssens, Ac, Igl, W, Hovingh, Gk, Hengstenberg, C, Havulinna, A, Hastie, Nd, Harris, Tb, Haritunians, T, Hall, A, Groop, Lc, Gonzalez, E, Freimer, Nb, Erdmann, J, Ejebe, Kg, Döring, A, Dominiczak, Af, Demissie, S, de Faire, U, Caulfield, Mj, Boekholdt, Sm, Assimes, Tl, Quertermous, T, Seielstad, M, Wong, Ty, Tai, E, Feranil, Ab, Kuzawa, Cw, Taylor HA, Jr, Gabriel, Sb, Holm, H, Gudnason, V, Krauss, Rm, Ordovas, Jm, Munroe, Pb, Tall, Ar, Hegele, Ra, Kastelein, Jj, Schadt, Ee, Strachan, Dp, Reilly, Mp, Samani, Nj, Schunkert, H, Cupples, La, Ridker, Pm, Rader, Dj, Kathiresan, S., Medical Research Council (MRC), Perry, John [0000-0001-6483-3771], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Semple, Robert [0000-0001-6539-3069], Griffin, Simon [0000-0002-2157-4797], Barroso, Ines [0000-0001-5800-4520], Soranzo, Nicole [0000-0003-1095-3852], Wheeler, Eleanor [0000-0002-8616-6444], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Zhao, Jing Hua [0000-0003-4930-3582], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Sandhu, Manjinder [0000-0002-2725-142X], Apollo - University of Cambridge Repository, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, Other departments, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Human genetics, Psychiatry, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Lääketieteen yksikkö - School of Medicine, University of Tampere, Institute for Molecular Medicine Finland, Hjelt Institute (-2014), Clinicum, Department of General Practice and Primary Health Care, Department of Public Health, Haartman Institute (-2014), Transplantation Laboratory, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Genetic Epidemiology, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., and O'Leary, DH.
Subjects: Netherlands Twin Register (NTR), Male, Insulin Resistance/genetics, VARIANTS, 0302 clinical medicine, POPULATION, African Americans, blood/genetics, 0303 health sciences, education.field_of_study, Adiponectin/blood, Adiponectin/genetics, Asian Continental Ancestry Group, Cholesterol, HDL/genetics, Diabetes Mellitus, Type 2/genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Global B Pgen Consortium, MAGIC investigators, 3. Good health, Cholesterol, Medicine, Adiponectin, Type 2, medicine.medical_specialty, HDL, Biolääketieteet - Biomedicine, Single-nucleotide polymorphism, DIAGRAM Consortium, White People, Molecular Genetics, GLGC Consortium, 03 medical and health sciences, Asian People, SDG 3 - Good Health and Well-being, GIANT Consortium, Diabetes Mellitus, Genetics, DIAGRAM+ Consortium, GENOME-WIDE ASSOCIATION, Polymorphism, education, Biology, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 0604 Genetics, Science & Technology, GLGC Investigators, nutritional and metabolic diseases, ta3121, medicine.disease, Obesity, Black or African American, blood/genetics, African Americans, Asian Continental Ancestry Group, Cholesterol, genetics, Diabetes Mellitus, genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance, genetics, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Endocrinology, Diabetes Mellitus, Type 2, Developmental Biology, Type 2/genetics, Cancer Research, Type 2 diabetes, QH426-470, 030204 cardiovascular system & hematology, LIPID CONCENTRATIONS, GENETICS & HEREDITY, Genetics (clinical), RISK, 2. Zero hunger, INSULIN-RESISTANCE, Glucose tolerance test, medicine.diagnostic_test, MAGIC Consortium, Single Nucleotide, ADIPOSE-TISSUE, CORONARY-ARTERY-DISEASE, Life Sciences & Biomedicine, Research Article, Clinical Research Design, GENETIC-BASIS, Population, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, ddc:610, 030304 developmental biology, RECEPTOR, Cholesterol, HDL, Human Genetics, HDL/genetics, 3121 General medicine, internal medicine and other clinical medicine, MuTHER Consortium, 3111 Biomedicine, Procardis Consortium, Insulin Resistance
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p, Author Summary Serum adiponectin levels are highly heritable and are inversely correlated with the risk of type 2 diabetes (T2D), coronary artery disease, stroke, and several metabolic traits. To identify common genetic variants associated with adiponectin levels and risk of T2D and metabolic traits, we conducted a meta-analysis of genome-wide association studies of 45,891 multi-ethnic individuals. In addition to confirming that variants at the ADIPOQ and CDH13 loci influence adiponectin levels, our analyses revealed that 10 new loci also affecting circulating adiponectin levels. We demonstrated that expression levels of several genes in these candidate regions are associated with serum adiponectin levels. Using a powerful novel method to assess the contribution of the identified variants with other traits using summary-level results from large-scale GWAS consortia, we provide evidence that the risk alleles for adiponectin are associated with deleterious changes in T2D risk and metabolic syndrome traits (triglycerides, HDL, post-prandial glucose, insulin, and waist-to-hip ratio), demonstrating that the identified loci, taken together, impact upon metabolic disease.
Published: 2012
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27. Individually Tailored Care Plan Improved Calcium Intake and Vitamin D Levels in Older Hip Fracture Patients.

Author: Pehkonen, M., Luukkaala, T., Kujala, M., and Nuotio, M.
Subjects: CALCIUM, VITAMIN D, HIP fractures, OSTEOPOROSIS, BONE fractures
Abstract: Introduction: Ensuring sufficient calcium intake and serum vitamin D levels is essential part of fracture care and secondary prevention of subsequent falls and fractures. Many hip fracture patients have low vitamin D levels (assessed by serum 25(OH)D) at presentation and the amount of dietary calcium intake is commonly not known. We studied the effect of an individual care plan on calcium intake and 25(OH)D levels in older hip fracture patients. Methods: The study comprised population-based sample of 1001 Finns aged 65 and over sustaining a low energy hip fracture between 2011 and 2018. Follow-up data at geriatric outpatient clinic 4-6 months post-fracture were available on 796 patients. We assessed 25(OH)D levels and calcium intake from food and supplements in the acute post-fracture period. Calcium and vitamin D supplements along with nutritional advice were tailored individually. According to national guidelines for osteoporosis, the aim of daily calcium intake was 1000 to 1500 mg and the target range for 25(OH)D 75-120 nmol/l. Calcium intake and 25(OH)D were re-evaluated at the outpatient follow-up. The patients were categorized into living in their own home with or without organized homecare, and living assisted or institutionalized. Results: The pre-fracture calcium intake was below recommendation in half (52%) of the patients. This was particularly evident in patients living in their own homes. In this group calcium intake improved significantly in the post-fracture period (median change 780 to 830 mg, interquartile ranges (IQRs) 5401200, 600-1040). In the group of assisted or institutionalized living calcium intake was already higher and did not improve significantly. Daily intake exceeded the recommendation in 16% of the patients. In 60% of the patients the 25(OH)D level was below the target range for osteoporosis and 36% had hypovitaminosis (<50 nmol/l). D vitamin supplement was in use in 40% before the fracture. In the post-fracture period 25(OH)D increased to the recommended therapeutic area in majority of patients living both in their own homes (median 25(OH)D 57 vs 87 nmol/l, IQR 38-79 vs 70-108) and assisted or institutionalized (median 25(OH)D 65 vs 86 nmol/l, IQR 50-86 vs 76-107). True vitamin D deficiency became less common towards the end of the study period. (P < 0.001). Conclusion: Individually tailored care plan improved calcium intake and vitamin D levels in older hip fracture patients. Primary prevention was more successful in patients living assisted or institutionalized. [ABSTRACT FROM AUTHOR]
Published: 2021
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28. Factors Associated With Urinary and Double Incontinence in a Geriatric Post-Hip Fracture Assessment in Older Women.

Author: Hellman-Bronstein, A., Luukkaala, T., Ala-Nissila, S., and Nuotio, M.
Subjects: OLDER women, MORTALITY, HIP fractures, HEALTH outcome assessment, HOSPITAL admission & discharge
Abstract: Introduction: Incontinence and hip fractures, both of which are more common among women than in men, are associated with numerous adverse outcomes, such as functional decline, institutionalization, and mortality. Incontinence is a known risk factor for falls. The aim of this study was to investigate the prevalence and changes of urinary incontinence (UI) and double incontinence (DI, concurrent UI and faecal incontinence) among older female hip fracture patients, and to identify factors associated with UI and DI six months post-fracture. Methods: A prospective population-based cohort study was conducted. All female patients aged ≥ 65 who were treated for their first hip fracture in Seinäjoki Central Hospital, Finland, between May 2008 and April 2018, were included. Pathologic and periprosthetic fractures were excluded. Continence status was elicited at baseline and six months postoperatively at our geriatric outpatient clinic where all participants underwent a comprehensive geriatric assessment (CGA) and a physiotherapist's examination. Multinomial logistic regression analyses were used. Results: Of the 910 patients included in the study, 70% were aged over 80 years, 25% had a cognitive disorder, 22% lived in an institution, 33% had poor nutrition, and 37% could not ambulate independently at baseline. Before the fracture 47% were continent, 45% had UI and 8% had DI and, 38%, 52% and 11% six months post-fracture, respectively. The continence status had deteriorated in 24% of the patients. In the multivariable-adjusted analyses, constipation (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.02-2.13) and depressive mood (OR 1.81, 95% CI 1.16-2.84) observed in the outpatient CGA were associated with UI, whereas prolonged use of urinary catheter during hospitalization (OR 2.33, 95% CI 1.31-4.14), non-independent mobility at baseline (OR 2.08, 95% CI 1.05-4.15) and poor nutrition observed in the outpatient CGA (OR 2.31, 95% CI 1.11-4.79) were associated with DI six months post-fracture. Conclusion: This study demonstrates a high prevalence of UI and DI in older female hip fracture patients. Both UI and DI were associated with modifiable risk factors, which should be targeted both during hospitalization and rehabilitation process as a part of secondary falls prevention. Patients with DI were found to be an especially vulnerable group. More efforts are needed to increase awareness of incontinence and its consequences and complications in older hip fracture patients. [ABSTRACT FROM AUTHOR]
Published: 2021
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29. Predictors of Institutionalization in an Older Population During a 13-Year Period: The Effect of Urge Incontinence

Author: Nuotio, M., primary, Tammela, T. L. J., additional, Luukkaala, T., additional, and Jylha, M., additional
Published: 2003
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30. Association of Smoking with Urgency in Older People

Author: Nuotio, M., primary, Jylhä, M., additional, Koivisto, A.-M., additional, and Tammela, T.L.J., additional
Published: 2001
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31. Association of urgency symptoms with self-rated health, mood and functioning in an older population.

Author: Nuotio M, Tammela TL, Luukkaala T, and Jylhä M
Abstract: BACKGROUND AND AIMS: Lower urinary tract symptoms (LUTS) with comorbidities are common in old age. The aim here was to investigate the associations of urgency symptoms with self-rated health, mood and functioning in a random older population adjusted for comorbid conditions. METHODS: A population-based cross-sectional survey was made involving 343 people (159 men and 184 women) aged 70 years and over. LUTS were categorized as symptoms with or without urgency. Perceived inconvenience from LUTS, self-rated health, mood, social activity and activities of daily living (ADL), instrumental activities of daily living (IADL) and mobility disability were the outcome measures. Ageand gender-adjusted and multivariate logistic regression models were constructed in order to examine the associations of urgency and non-urgency symptoms with the outcomes. The covariates were age, gender, and self-reported cardiovascular, musculoskeletal, neurological and other chronic diseases. RESULTS: Perceived inconvenience from urgency symptoms was more frequent than that from non-urgency symptoms (64% vs 20%, p<0.001). In the age- and gender-adjusted logistic regression models, LUTS with urgency were associated with poor self-rated health (OR [odds ratio] 2.35; 95% CI [confidence interval] 1.06-5.20), depressive mood (OR 7.29; 95% CI 2.91-18.30), ADL (OR 2.33; 95% CI 1.10-4.92), IADL (OR 2.16; 95% CI 1.19-3.92) and mobility disability (OR 2.44; 95% CI 1.37-4.36). LUTS without urgency were associated with depressive mood (OR 5.02; 95% CI 1.97-12.82) and mobility disability (OR 1.97; 95% CI 1.10-3.53). In the multivariate analyses in which comorbid conditions were added to the model, the associations of non-urgency and urgency symptoms persisted only with depressive mood (OR 4.00; 95% CI 1.52-10.53 and OR 6.16; 95% CI 2.39-15.84, respectively). CONCLUSION: Urgency symptoms are associated with poor self-rated health, depressive mood and disability in older people. There is an independent association between both urgency and non-urgency LUTS and depressive mood. A careful assessment of the mental state of older individuals with LUTS is warranted. [ABSTRACT FROM AUTHOR]
Published: 2007
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32. Health problems associated with lower urinary tract symptoms in older women: a population-based study.

Author: Nuotio M, Jylha M, Luukkaala T, and Tammela TLJ
Abstract: OBJECTIVE: To identify health problems associated with lower urinary tract symptoms (LUTS) in an older female population. DESIGN: Population-based cross-sectional survey. SETTING: Third wave for the Tampere Longitudinal Study on Ageing (TamELSA) in 1999-2000. SUBJECTS: A total of 203 women aged 70 years and over. MAIN OUTCOME MEASURES: LUTS categorized as urge symptoms only, voiding symptoms only, and urge and voiding symptoms combined. The health indicators were polypharmacy (> 3 medications), use of sleeping medication, constipation, treated urinary tract infections (UTIs), and neurological, cardiovascular, and musculoskeletal diseases. RESULTS: Of the respondents 16% reported urge symptoms, 22% voiding symptoms, and 26% combined symptoms. In the multinomial logistic regression models, constipation and musculoskeletal diseases were significantly associated with voiding symptoms (OR 4.33; 95% CI 1.62-11.57 and OR 5.25; 95% CI 1.94-14.18, respectively) and with combined symptoms (OR 4.33; 95% CI 1.67-11.21 and OR 2.84; 95% CI 1.17-6.89, respectively). UTIs (OR 2.78; 95% CI 1.09-7.08) were associated with combined symptoms. CONCLUSIONS: Voiding symptoms comprise a significant part of lower urinary tract symptomalogy in older women. Although constipation, musculoskeletal diseases, and UTIs are the main health problems associated with LUTS, other concomitant diseases and medications also need to be assessed in older female patients with LUTS. [ABSTRACT FROM AUTHOR]
Published: 2005
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33. A thermodynamic analysis of the binary alloy systems Cu-Cr, Cu-Nb and Cu-V

Author: Hämäläinen, M., primary, Jääskeläinen, K., additional, Luoma, R., additional, Nuotio, M., additional, Taskinen, P., additional, and Teppo, O., additional
Published: 1990
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34. Urinary incontinence in a Finnish population aged 70 and over: prevalence of types, associated factors and self-reported treatments.

Author: Nuotio M, Jylhä M, Luukkaala T, and Tammela TLJ
Abstract: OBJECTIVE: To describe the prevalence, associated factors and self-reported treatments of different types of incontinence in a random older population. DESIGN: A population-based cross-sectional survey. SETTING: Third wave for the Tampere Longitudinal Study on Ageing (TamELSA) in 1999. SUBJECTS: 171 men and 227 women aged 70 and over. MAIN OUTCOME MEASURES: Urge and mixed incontinence combined and associated health and social indicators. RESULTS: The prevalence of stress, urge and mixed incontinence was 2%, 17% and 6%, respectively, in men and 23%, 6% and 30%, respectively, in women. In the logistic regression analyses adjusted for age, urge and mixed incontinence in women were associated with living in an institution (OR [odds ratiol 13.55), comorbidity (OR 1.94), ADL (activities of daily living) disability (OR 3.55), depressive mood (OR 2.49) and fecal incontinence (OR 7.84), while in men an association was found between urge and mixed incontinence and ADL disability (OR 2.59) and depressive mood (OR 2.69). All the men living in an institution were incontinent of urine. Of the incontinent women, 46% used diapers, but collecting devices were rare in men. CONCLUSION: The results emphasise the significance and multifactorial nature of the urge component in geriatric incontinence, which should be considered in both geriatric and general practice. [ABSTRACT FROM AUTHOR]
Published: 2003

35. Inter- and Subtrochanteric vs Femoral Neck Fractures are Associated With Poorer Mobility and Physical Performance After Hip Fracture.

Author: Kujala, M. A., Luukkaala, T., Stenholm, S., and Nuotio, M. S.
Subjects: HIP fractures, POSTOPERATIVE period, OLDER patients, HEALTH outcome assessment
Abstract: Introduction: Hip fracture often leads to decline in mobility and increased need for assistance in activities of daily living (ADL). The purpose of our study was to elucidate post-fracture functional outcome and physical performance according to hip fracture type. Methods: The study material comprised all 2052 consecutive patients aged 65 and over who sustained their first hip fracture between September 2007 and February 2018 in the Hospital District of Southern Ostrobothnia, Finland. Fractures of the upper femur were categorized as neck of femur, intertrochanteric and subtrochanteric fracture. Data were collected on admission and with telephone interview by a geriatric nurse 4 months postoperatively. Follow-up visit at the geriatric outpatient clinic with comprehensive geriatric assessment (CGA) including ADL assessments was carried out 4 to 6 months post-fracture. The CGA was preceded by a physiotherapist's examination including physical performance tests such as the Timed Up and Go (TUG), Elderly Mobility Scale (EMS) and measurement for grip strength. Logistic regression analyses were used. Results: Of the 2052 patients 62% had a neck of femur, 32% an intertrochanteric and 6% a subtrochanteric fracture. Of patient's characteristics age, living arrangements, American Society of Anesthesiologists (ASA) grade, diagnosis of cognitive disorder and need of mobility aid were significantly associated with other hip fracture type than the femoral neck fracture. During the follow-up, mobility level had deteriorated in 39% of the femoral neck, 52% of the intertrochateric and 51% of the subtrochanteric fracture patients. Change in mobility was most significant in patients moving independently before the fracture. Advanced age and abnormal/low results in physical performance tests and low ADL performance were more common in patients with other hip fracture type than the femoral neck fracture. In the multivariable analyses adjusted for age, gender and mobility level at baseline, poor results in each of the physical performance tests and ADLs were significantly associated with intertrochanteric vs femoral neck fractures. Conclusion: Femoral neck fracture patients are more likely to regain their pre-fracture mobility level after hip fracture compared to inter- and subtrochanteric fractures but mobility decline is common in all hip fracture types. In order to regain pre-fracture mobility, all hip fracture patients need intensive rehabilitation. [ABSTRACT FROM AUTHOR]
Published: 2021
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36. Nutritional aspects in perioperative care

Author: Helminen, H. (Heli), Saarnio, J. (Juha), and Nuotio, M. (Maria)
Subjects: preoperative carbohydrate drink, lonkkamurtumapotilas, päiväkirurginen sappileikkaus, carbohydrate loading, day-case cholecystectomy, screening of malnutrition, hiilihydraattitankkaus, hip fracture patient, leikkausta edeltävä hiilihydraattijuoma, ravitsemustestaus, malnutrition, vajaaravitsemus
Abstract: This thesis investigates the role of nutrition in perioperative care; the effects of preoperative carbohydrate loading and whether nutrition screening tests can detect malnutrition and determine the prognosis of recovery from hip fracture in older patients. In the randomized, controlled trial (RCT) overnight fasting was compared to overnight intravenous (iv) glucose and carbohydrate-rich drink (CHD) in the morning. The patients’ subjective feelings of wellbeing were elicited using a visual analogue scale (VAS). In the second RCT overnight fasting was compared to CHD in day-case cholecystectomy patients. In the observational nutrition studies status of hip fracture patients was evaluated using the Mini Nutritional Assessment (MNA) short (SF) and long version (LF), serum albumin (S-Alb) and the Nutritional Risk Screening 2002 (NRS2002). The outcomes were the length of hospitalization, readmissions, changes in mobility and living arrangements and mortality. The changes in nutritional status and its association with the comprehensive geriatric assessment (CGA) were evaluated after six months follow-up. CHD relieved thirst better than iv solution. The CHD group was less hungry than the fasting group before the operation. Day-case cholecystectomy patients did not benefit from CHD. Of the hip fracture patients 25%, 45% and 55 % had poor nutritional status at fractura time according to the NRS2002, S-Alb and MNA tests, respectively. Poor nutritional status in the MNAs predicted prolonged hospitalization, readmissions, need for more supportive living arrangements, mobility limitations and mortality. Low S-Alb predicted mortality. The NRS2002 predicted the outcomes poorly. There was a clear deterioration in nutritional status during follow-up. Many factors in the CGA were associated with poor nutrition status: depressed mood, cognitive impairment, weakened grip strength, difficulties in activities of daily living. CHD is safe and may promote wellbeing while waiting for surgery. It is useless in recovery from day-case cholecystectomy. About half of hip fracture patients have poor nutritional status and this can inhibit recovery. The MNA-SF appeared to be the most useful nutritional screening test. Healthcare organizations should identify patients at nutritional risk leading to nutritional care plans. Tiivistelmä Väitöskirjassa tarkastellaan ravitsemusnäkökulmia liittyen leikkaushoitoon. Kahdessa satunnaistetussa, kontrolloidussa tutkimuksessa (RCT) verrattiin hiilihydraattitankkausta paastoamiseen ennen suunniteltua leikkausta. Toisena aiheena tutkittiin ravitsemusseulontatestien toimivuuttaa tunnistaa vanhuksen vajaaravitsemus ja ennustaa toipumista lonkkamurtumasta. Verrattiin suonensisäisen (iv), juomalla annetun hiilihydraattitankkauksen (CHD) ja paaston vaikutusta vointiin leikkausta odottaessa. Vointia arvioitiin Visual Analogue Scale (VAS) mittarilla. Toisessa osatyössä verrattiin paaston ja CHD vaikutusta päiväkirurgisilla sappileikkauspotilailla. Lonkkamurtumapotilaiden ravitsemustilaa arvioitiin neljällä testillä: Mini Nutritional Assessment (MNA) lyhyt (SF) ja pitkä versio (LF), seerumin albumiini (S-Alb) ja Nutritional Risk Screening 2002 (NRS2002). Toipumismittareina käytettiin sairaalahoidon pituutta, uusia hoitojaksoja, liikuntakyvyn, asumismuodon muutosta ja kuolleisuutta. Lisäksi selvitettiin ravitsemustilan muutosta ja yhteyttä laajan geriatrisen arvioinnin (CGA) tuloksiin puoli vuotta murtumasta. CHD lievensi janoa paremmin kuin iv-liuos. CHD:tä saaneet olivat ennen leikkausta vähemmän nälkäisiä kuin paastonneet. Päiväkirurgiset potilaat eivät hyötyneet CHD:stä. Ravitsemusseulontatutkimuksissa oli murtumahetkellä potilaista vajaaravitsemusriskissä tai vajaaravittuja 25 % NRS2002-testillä, 45 % S-Alb:lla ja 55 % MNA-testeillä arvioituna. Heikentynyt ravitsemustila MNA-testien perusteella ennusti sairaalahoidon pitkittymistä, uusia hoitojaksoja, tuetumman asumismuodon tarvetta, liikuntakyvyn heikkenemistä ja kuolleisuutta. Matala S-Alb ennusti kuolleisuutta. NRS2002 ennusti huonosti toipumistuloksia. Ravitsemustila huononi useilla seuranta-aikana ja oli yhteydessä masennukseen, muistisairauteen, heikkoon käden puristusvoimaan ja heikentyneisiin tuloksiin toimintakykytesteissä CGA:ssa. CHD leikkauspäivän aamuna on turvallinen ja voi vähentää epämiellyttävää oloa leikkaussaliin odottaessa. Toipumiseen päiväkirurgisesta sappileikkauksesta juoma ei merkittävästi vaikuta. Lonkkamurtumavanhuksista noin puolella on alentunut ravitsemustila murtuman sattuessa ja tämä vaikuttaa heikentävästi toipumiseen. Seulontatesteistä MNA-SF on käyttökelpoisin. Terveydenhoitojärjestelmässä tulisi olla ohjeet ravitsemustilan seulonnasta ja vajaaravitsemuksen hoidosta.
Published: 2020

37. Adiposity as a cause of cardiovascular disease: a Mendelian randomization study

Author: Aarno Palotie, Tõnu Esko, Christopher P. Nelson, Christian Gieger, Vilmantas Giedraitis, Jarmo Virtamo, Inga Prokopenko, Alistair S. Hall, Jean Ferrières, John Whitfield, Marika Kaakinen, Cornelia M. van Duijn, Samuli Ripatti, M. Arfan Ikram, Harmen H.M. Draisma, Massimo Mangino, David P. Strachan, Martin D. Tobin, Paul S. de Vries, Albert Hofman, Renée F A G de Bruijn, Nancy L. Pedersen, Ann-Christine Syvänen, Alun Evans, Bruno H. Stricker, Beben Benyamin, Markus Perola, Antti-Pekka Sarin, Tove Fall, Lars Lind, Francesco Gianfagna, Abbas Dehghan, David-Alexandre Trégouët, Veikko Salomaa, Kati Kristiansson, Eco J. C. de Geus, Michael Kobl, Oscar H. Franco, Antti Jula, Mart Kals, Sara M. Willems, Ville Huikari, Marjo-Riitta Järvelin, Krista Fischer, Reedik Mägi, Philippe Amouyel, Maris Kuningas, Andres Metspalu, Aki S. Havulinna, Sara Hägg, André G. Uitterlinden, Paolo Brambilla, Alexander Ploner, Kari Kuulasmaa, Erik Ingelsson, Jaakko Kaprio, Marja-Liisa Nuotio, Mark I. McCarthy, Nilesh J. Samani, Tim D. Spector, Dominique Arveiler, Patrik K. E. Magnusson, Frank Kee, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Epidemiology, Neurology, Internal Medicine, Hägg, S, Fall, T, Ploner, A, Mägi, R, Fischer, K, Draisma, H, Kals, M, de Vries, P, Dehghan, A, Willems, S, Sarin, A, Kristiansson, K, Nuotio, M, Havulinna, A, de Bruijn, R, Ikram, M, Kuningas, M, Stricker, B, Franco, O, Benyamin, B, Gieger, C, Hall, A, Huikari, V, Jula, A, Järvelin, M, Kaakinen, M, Kaprio, J, Kobl, M, Mangino, M, Nelson, C, Palotie, A, Samani, N, Spector, T, Strachan, D, Tobin, M, Whitfield, J, Uitterlinden, A, Salomaa, V, Syvänen, A, Kuulasmaa, K, Magnusson, P, Esko, T, Hofman, A, de Geus, E, Lind, L, Giedraitis, V, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Gianfagna, F, Brambilla, P, Ripatti, S, van Duijn, C, Metspalu, A, Prokopenko, I, Mccarthy, M, Pedersen, N, Ingelsson, E, Hägg, Sara, Fall, Tove, Ploner, Alexander, Mägi, Reedik, Benyamin, Beben, Ingelsson, Erik, and European Network Genetic Genomic Epidemiology (ENGAGE) consortium
Subjects: Male, medicine.medical_specialty, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Cross-sectional study, Epidemiology, Mendelian Randomization Causal Analysis, body mass index, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, cardiovascular disease, Internal medicine, Mendelian randomization, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Adiposity, 2. Zero hunger, business.industry, Mendelian Randomization Analysis, Cardiovascular Disease, Mendelian Randomization, General Medicine, Middle Aged, medicine.disease, Cardiovascular disease, epidemiology, 3. Good health, Endocrinology, Blood pressure, Cross-Sectional Studies, Cardiovascular Diseases, Heart failure, Cardiology, Female, business, Body mass index
Abstract: BACKGROUND: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods. METHODS: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes. RESULTS: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9·10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9·10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3·10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD. CONCLUSIONS: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.
Published: 2015
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38. Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

Author: Christopher P. Nelson, Valeriya Lyssenko, Philippe Amouyel, Alistair S. Hall, Andres Metspalu, Giovanni Veronesi, Mark I. McCarthy, Peter M. Nilsson, Nilesh J. Samani, Marika Kaakinen, Jean Ferrières, Antti-Pekka Sarin, Veikko Salomaa, Tove Fall, Cristina Menni, Jarmo Virtamo, Cornelia M. van Duijn, Samuli Ripatti, Tõnu Esko, Oscar H. Franco, David P. Strachan, Martin D. Tobin, John Yarnell, Beben Benyamin, Aki S. Havulinna, André G. Uitterlinden, M. Arfan Ikram, Christian Herder, Michael Kobl, Abbas Dehghan, Wolfgang Koenig, Nicholas G. Martin, Patrik K. E. Magnusson, Kirsi H. Pietiläinen, Ville Huikari, Massimo Mangino, John Whitfield, Paul S. de Vries, Sara M. Willems, Brenda W.J.H. Penninx, Jaakko Kaprio, Peter Lichtner, Marja-Liisa Nuotio, Leif Groop, Albert Hofman, Alexander Ploner, Konstantin Strauch, Kari Kuulasmaa, Jean Dallongeville, Mart Kals, Dominique Cottel, Dorret I. Boomsma, Paolo Brambilla, Maris Kuningas, Dominique Arveiler, Harmen H.M. Draisma, Tim D. Spector, Aarno Palotie, Claes Ladenvall, Karri Silventoinen, Luis A. Moreno, Lars Lind, Christian Gieger, Marjo-Riitta Järvelin, Krista Fischer, Ann-Christine Syvänen, Alun Evans, Vilmantas Giedraitis, Annette Peters, Vanessa Legry, Erik Ingelsson, Harald Grallert, Aline Meirhaeghe, Sara Hägg, Kati Kristiansson, Grant W. Montgomery, Renée F.A.G. de Bruijn, Marcela González-Gross, Inga Prokopenko, Nancy L. Pedersen, David-Alexandre Trégouët, Reedik Mägi, Mikael Åkerlund, Bruno H. Stricker, Markus Perola, Louisa Goumidi, Kauko Heikkilä, Antti Jula, Surgery, Epidemiology, Neurology, Internal Medicine, Radiology & Nuclear Medicine, Fall, Tove, Hägg, Sara, Ploner, Alexander, Mägi, Reedik, Benyamin, Beben, Ingelsson, Erik, ENGAGE Consortium, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Fall, T, Hägg, S, Ploner, A, Mägi, R, Fischer, K, Draisma, H, Sarin, A, Benyamin, B, Ladenvall, C, Åkerlund, M, Kals, M, Esko, T, Nelson, C, Kaakinen, M, Huikari, V, Mangino, M, Meirhaeghe, A, Kristiansson, K, Nuotio, M, Kobl, M, Grallert, H, Dehghan, A, Kuningas, M, de Vries, P, de Bruijn, R, Willems, S, Heikkilä, K, Silventoinen, K, Pietiläinen, K, Legry, V, Giedraitis, V, Goumidi, L, Syvänen, A, Strauch, K, Koenig, W, Lichtner, P, Herder, C, Palotie, A, Menni, C, Uitterlinden, A, Kuulasmaa, K, Havulinna, A, Moreno, L, Gonzalez Gross, M, Evans, A, Tregouet, D, Yarnell, J, Virtamo, J, Ferrières, J, Veronesi, G, Perola, M, Arveiler, D, Brambilla, P, Lind, L, Kaprio, J, Hofman, A, Stricker, B, van Duijn, C, Ikram, M, Franco, O, Cottel, D, Dallongeville, J, Hall, A, Jula, A, Tobin, M, Penninx, B, Peters, A, Gieger, C, Samani, N, Montgomery, G, Whitfield, J, Martin, N, Groop, L, Spector, T, Magnusson, P, Amouyel, P, Boomsma, D, Nilsson, P, Järvelin, M, Lyssenko, V, Metspalu, A, Strachan, D, Salomaa, V, Ripatti, S, Pedersen, N, Prokopenko, I, Mccarthy, M, Ingelsson, E, Psychiatry, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
Subjects: Netherlands Twin Register (NTR), Male, medicine.medical_specialty, Aging, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Endocrinology, Diabetes and Metabolism, Blood Pressure, chemistry.chemical_compound, Insulin resistance, Sex Factors, SDG 3 - Good Health and Well-being, Internal medicine, Mendelian randomization, Internal Medicine, medicine, Humans, Insulin, Triglycerides, Adiposity, adiposity, genetic markers, adiposity, blood pressure, glycemic indices, circulating lipid levels, arkers of inflammation, liver disease, biology, business.industry, Cholesterol, Interleukin-6, C-reactive protein, Cholesterol, HDL, Genetics/Genomes/Proteomics/Metabolomics, Middle Aged, medicine.disease, Obesity, 3. Good health, cardiovascular diseases, sex factors, Glycemic index, Endocrinology, Blood pressure, C-Reactive Protein, chemistry, Cardiovascular Diseases, biology.protein, Female, business, Body mass index
Abstract: Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10−107) and stratified analyses (all P < 3.3 × 10−30). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the
Published: 2015
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39. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, Dmitry, Winkler, Thomas W, Workalemahu, Tsegaselassie, Hartman, Catharina A, Duncan, Emma L, Ntzani, Evangelia E, Oei, Ling, Albagha, Omar M E, Amin, Najaf, Kemp, John P, Koller, Daniel L, Li, Guo, Liu, Ching-Ti, Minster, Ryan L, Hassinen, Maija, Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su-Mei, Yerges-Armstrong, Laura M, Zheng, Hou-Feng, Alonso, Nerea, Eriksson, Joel, Kammerer, Candace M, Kaptoge, Stephen K, Hayward, Caroline, Leo, Paul J, Thorleifsson, Gudmar, Wilson, Scott G, Wilson, James F, Aalto, Ville, Alen, Markku, Aragaki, Aaron K, Aspelund, Thor, Center, Jacqueline R, Dailiana, Zoe, Heikkilä, Kauko, Duggan, David J, Garcia, Melissa, Garcia-Giralt, Natàlia, Giroux, Sylvie, Hallmans, Göran, Hocking, Lynne J, Husted, Lise Bjerre, Jameson, Karen A, Khusainova, Rita, Kim, Ghi Su, Herzig, Karl-Heinz, Kooperberg, Charles, Koromila, Theodora, Kruk, Marcin, Laaksonen, Marika, Lacroix, Andrea Z, Lee, Seung Hun, Leung, Ping C, Lewis, Joshua R, Masi, Laura, Mencej-Bedrac, Simona, Helmer, Quinta, Nguyen, Tuan V, Nogues, Xavier, Patel, Millan S, Prezelj, Janez, Rose, Lynda M, Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V, Svensson, Olle, Trompet, Stella, Hillege, Hans L, Trummer, Olivia, van Schoor, Natasja M, Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M, Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Holmen, Oddgeir, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Hunt, Steven C, Langdahl, Bente Lomholt, Leslie, William D, Lips, Paul, Ljunggren, Östen, Lorenc, Roman S, Marc, Janja, Mellström, Dan, Obermayer-Pietsch, Barbara, Olmos, José M, Pettersson-Kymmer, Ulrika, Isaacs, Aaron, Reid, David M, Riancho, José A, Ridker, Paul M, Rousseau, François, Slagboom, P Eline, Tang, Nelson L S, Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, María T, Wu, Joseph M W, Ittermann, Till, Aulchenko, Yurii S, Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gómez, Carolina, James, Alan L, Palsson, Stefan Th, Reppe, Sjur, Rotter, Jerome I, Sigurdsson, Gunnar, van Meurs, Joyce B J, Verlaan, Dominique, Williams, Frances M K, Wood, Andrew R, Zhou, Yanhua, Gautvik, Kaare M, Johansson, Ingegerd, Pastinen, Tomi, Raychaudhuri, Soumya, Cauley, Jane A, Chasman, Daniel I, Clark, Graeme R, Cummings, Steven R, Danoy, Patrick, Dennison, Elaine M, Eastell, Richard, Eisman, John A, Juliusdottir, Thorhildur, Gudnason, Vilmundur, Hofman, Albert, Jackson, Rebecca D, Jones, Graeme, Jukema, J Wouter, Khaw, Kay-Tee, Lehtimäki, Terho, Liu, Yongmei, Lorentzon, Mattias, McCloskey, Eugene, Kalafati, Ioanna-Panagiota, Mitchell, Braxton D, Nandakumar, Kannabiran, Nicholson, Geoffrey C, Oostra, Ben A, Peacock, Munro, Pols, Huibert A P, Prince, Richard L, Raitakari, Olli, Reid, Ian R, Robbins, John, Kinnunen, Leena, Sambrook, Philip N, Sham, Pak Chung, Shuldiner, Alan R, Tylavsky, Frances A, van Duijn, Cornelia M, Wareham, Nick J, Cupples, L Adrienne, Econs, Michael J, Evans, David M, Harris, Tamara B, Koenig, Wolfgang, Kung, Annie Wai Chee, Psaty, Bruce M, Reeve, Jonathan, Spector, Timothy D, Streeten, Elizabeth A, Zillikens, M Carola, Thorsteinsdottir, Unnur, Ohlsson, Claes, Karasik, David, Richards, J Brent, Kooner, Ishminder K, Brown, Matthew A, Stefansson, Kari, Uitterlinden, André G, Ralston, Stuart H, Ioannidis, John P A, Kiel, Douglas P, Rivadeneira, Fernando, Sandholm, Niina, Salem, Rany M, McKnight, Amy Jayne, Kratzer, Wolfgang, Brennan, Eoin P, Forsblom, Carol, Isakova, Tamara, McKay, Gareth J, Williams, Winfred W, Sadlier, Denise M, Mäkinen, Ville-Petteri, Swan, Elizabeth J, Palmer, Cameron, Boright, Andrew P, Lamina, Claudia, Ahlqvist, Emma, Deshmukh, Harshal A, Keller, Benjamin J, Huang, Huateng, Ahola, Aila, Fagerholm, Emma, Gordin, Daniel, Harjutsalo, Valma, He, Bing, Heikkilä, Outi, Buchkovich, Martin L, Leander, Karin, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Saraheimo, Markku, Sarti, Cinzia, Lee, Nanette R, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Wadén, Johan, Gill, Geoffrey V, Lichtner, Peter, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Ladenvall, Claes, Alhenc-Gelas, François, Lind, Lars, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Möllsten, Anna, Cimponeriu, Dan, Lindström, Jaana, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Colhoun, Helen M, Panduru, Nicolae Mircea, Lobbens, Stéphane, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Waggott, Daryl, Paterson, Andrew D, Savage, David A, Bain, Stephen C, Martin, Finian, Hirschhorn, Joel N, Godson, Catherine, Florez, Jose C, Groop, Per-Henrik, Maxwell, Alexander P, Willer, Cristen J, Schmidt, Ellen M, Mach, François, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Mora, Samia, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Magnusson, Patrik Ke, Chang, Hsing-Yi, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Ferreira, Teresa, Fischer, Krista, Mahajan, Anubha, Fontanillas, Pierre, Fraser, Ross M, Freitag, Daniel F, Gurdasani, Deepti, Hyppönen, Elina, Jackson, Anne U, Johansson, Åsa, Johnson, Toby, Heard-Costa, Nancy L, McArdle, Wendy L, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Mihailov, Evelin, Montasser, May E, Menni, Cristina, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K, Shah, Sonia, Merger, Sigrun, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Been, Latonya F, Bolton, Jennifer L, Milani, Lili, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex S F, Döring, Angela, Elliott, Paul, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Mills, Rebecca, Gigante, Bruna, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, 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P., Esko, T., Fall, T., Chen, H., Robertson, N., Rybin, D., Chines, PS., Song, K., An, P., Marullo, L., Jansen, H., Oldehinkel, AJ., North, KE., Forouhi, NG., Edkins, S., Varga, TV., Oksa, H., Antonella, M., Kong, A., Herder, C., Antti, J., Miljkovic, I., Atalay, M., Kiess, W., James, AL., Smit, JH., Campbell, S., Fowkes, GR., Basart, HV., Rathmann, W., Maerz, W., Province, MA., Watanabe, RM., de Geus EJ., Penninx, BW., Oostra, B., Toenjes, A., Peyser, PA., Körner, A., Keinanen-Kiukaanniemi, SM., Saaristo, TE., Boomsma, D., Cucca, F., Balkau, B., Froguel, P., Jarvelin, MR., Bouatia-Naji, N., Ahmadi, KR., Ainali, C., Barrett, A., Bataille, V., Bell, JT., Buil, A., Dermitzakis, ET., Dimas, AS., Durbin, R., Glass, D., Hassanali, N., Hedman£££Åsa K£££ ÅK., Ingle, C., Keildson, S., Knowles, D., Krestyaninova, M., Lowe, CE., Meduri, E., di Meglio, P., Min, JL., Montgomery, SB., Nestle, FO., Nica, AC., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, SY., Small, KS., Surdulescu, G., Travers, ME., Tsaprouni, L., Tsoka, S., Wilk, A., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., Heiss, G., Taylor, K., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Crawford, D., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Ritchie, M., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Peters, U., Anderson, G., Carlson, C., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, W., Albrecht, E., Alizadeh, BZ., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Keyzer, J., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Department of Clinical Sciences, Lund University [Lund], Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Umeå University, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, Limnology, Ecology, Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Institute of Medical Informatics, Biometry and Epidemiology, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Space Sciences Laboratory [Berkeley] (SSL), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, King‘s College London, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Department of Pharmacy Sciences, Creighton University Medical Center, Medical Department III, Universität Leipzig, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Epidemiology, Erasmus Medical Centre, Netherlands Genomics Initiative (NGI), Netherlands Genomics Initiative, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Public Health and Clinical Medicine, Medstar Research Institute, Genetics and Pathology, Finnish Institute of Occupational Health, Epidemiology, University Medical Centre Groningen, Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, University of California [Irvine] (UC Irvine), Department of Odontology, Cariology, Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Division of Cardiology, Geneva University Hospital (HUG), Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Anaesthesia and Intensive care, Royal Aberdeen Childrens Hospital, UCL Institute of neurology, UCL Institute of Neurology, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], 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= University of Helsinki, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, MRC epidemiology Unit, Institute of Epidemiology, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Oncology, Queensland Brain Institute, University of Queensland [Brisbane], Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, 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(BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Landsteiner Laboratory, Clinical Haematology, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Lund University Diabetes Centre-Lund University [Lund], Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Technical University of Denmark [Lyngby] (DTU), Université de Lausanne (UNIL), Universität Duisburg-Essen [Essen], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California [Berkeley], University of California-University of California, Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of California [Irvine] (UCI), German Research Center for Environmental Health, University of Bonn, Czech Academy of Sciences [Prague] (ASCR), Yale University School of Medicine, University of Oxford [Oxford], German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Laval University, Laval University [Québec], Turku University Hospital, Lausanne university hospital, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Helmholtz-Zentrum München (HZM), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Internal Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Medical Informatics, Obstetrics & Gynecology, Lund University [Lund]-Lund University Diabetes Centre, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institute of Medicine-University of Gothenburg (GU), Signalisation et Transports Ioniques Membranaires ( STIM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Technical University of Denmark [Lyngby] ( DTU ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Department of Medical Epidemiology and Biostatistics ( MEB ), University of Lausanne, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC, Space Sciences Laboratory [Berkeley] ( SSL ), Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), University of Leipzig, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Epidemiology [Neuherberg] ( EPI ), University of California [Irvine] ( UCI ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Geneva University Hospital ( HUG ), Bonn Universität [Bonn], Indian Institute of Technology Kanpur ( IIT Kanpur ), The University of North Carolina at Chapel Hill, Université de Bonn, Wellcome Trust Sanger Institute, Harvard University School of Public Health, Czech Academy of Sciences [Prague] ( ASCR ), deCODE genetics, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Yale School of Medicine, National Heart and Lung Institute ( NHLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, University Medical Center Groningen, University of Cambridge [UK] ( CAM ), Wellcome Trust Centre for Human Genetics, University of Pisa [Pisa], University of Cambridge [UK] ( CAM ) -Institute of Metabolic Science, German Research Center for Environmental Health-Helmholtz-Zentrum München ( HZM ), University of Otago, University of Greifswald, University College of London [London] ( UCL ), National Institute for Health and Welfare, Queen's University [Belfast] ( QUB ), University of Hawaii at Manoa ( UHM ), University of Gothenburg ( GU ) -Institute of Medicine, Recherches en Psychopathologie, nouveaux symptômes et lien social ( EA 4050 ), Université de Poitiers-Université de Brest ( UBO ) -Université Catholique de l'Ouest-Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Finland Institute for Molecular Medicine ( FIMM ), Georgia Prevention Institute, Netherlands Consortium for Healthy Aging, Helmholtz-Zentrum München ( HZM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Massachusetts General Hospital, Children's Hospital, Boston, Broad Institute, Cambridge, MA, The University of North Carolina at Chapel Hill-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Shungin D, Winkler TW, Adipogen, Consortium, Cardiogramplusc4d, Consortium, Ckdgen, Consortium, Gefos, Consortium, Genie, Consortium, Glgc, Icbp, International, Endogene Consortium, Lifelines, Cohort Study, Magic, Investigator, Muther, Consortium, Consortium, Page, ReproGen Consortium, Amouyel P, D'Adamo, ADAMO PIO, Gasparini, Paolo, Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Hypponen, Elina, Mohlke, Karen L, ADIPOGEN Consortium, Int Endogene Consortium, Lee Kong Chian School of Medicine (LKCMedicine), Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, Cooper, R, Dedoussis, G, Ferrucci, L, Froguel, P, Grabe, H, Hamsten, A, Hui, J, Hveem, K, Jöckel, K, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, März, W, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Pe'Russe, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sinisalo, J, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, 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de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Döring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Wright, A, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Völzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Krämer, B, Portas, L, Ford, I, Buckley, B, Adam, M, Thun, G, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Gasparini, P, Pirastu, M, Jukema, J, Probst Hensch, N, Toniolo, D, Coresh, J, Schmidt, R, Kardia, S, Curhan, G, Gyllensten, U, Franke, A, Rettig, R, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, van der Harst, P, Arking, D, Franceschini, N, Hernandez, D, Townsend, R, Lumley, T, Kestenbaum, B, Haritunians, T, Waeber, G, Lu, X, Leak, T, Aasarød, K, Skorpen, F, Baumert, J, Devuyst, O, 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Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Würtz, P, Ong, R, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Dominiczak, A, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Anderson, C, Gordon, S, Guo, Q, Henders, A, Lambert, A, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Alizadeh, B, de Boer, R, Boezen, H, van der Klauw, M, Ormel, J, Postma, D, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Lecoeur, C, Johnson, P, Hottenga, J, Salo, P, Bielak, L, Zhao, W, Horikoshi, M, Navarro, P, Chen, H, Rybin, D, Song, K, An, P, Marullo, L, Jansen, H, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Toenjes, A, Peyser, P, Körner, A, Cucca, F, Balkau, B, Bouatia Naji, N, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Hedman, Å, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Higashio, J, Williams, R, Nato, A, Ambite, J, Manolio, T, Hindorff, L, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown Gentry, K, Thornton Wells, T, Dumitrescu, L, Jeff, J, Bush, W, Mitchell, S, Goodloe, R, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Zheng, W, Spencer, K, Pendergrass, S, Wilkens, L, Park, L, Tiirikainen, M, Kolonel, L, Lim, U, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Schumacher, F, Anderson, G, Carlson, C, Prentice, R, Wu, C, Carty, C, Gong, J, Rosse, S, Young, A, Haessler, J, Kocarnik, J, Lin, Y, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chanock, S, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hall, P, Hankinson, S, Hass, M, Heath, A, Janssens, A, Keyzer, J, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Medland, S, Melzer, D, Newman, A, Paré, G, Peeters, P, Pop, V, Räikkönen, K, Salumets, A, Smith, J, Stacey, S, Starr, J, Stathopoulou, M, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Wallaschofski, H, Widen, E, Wijnands van Gent, C, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Feenstra, B, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Easton, D, Foroud, T, Geller, F, Kilpeläinen, T, Li, S, Melbye, M, Murray, J, Murray, S, Ness, A, Northstone, K, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segrè, A, Sovio, U, Srinivasan, S, Tammesoo, M, Tyrer, J, Weedon, M, Young, L, Bierut, L, Boyd, H, Psychiatry, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
Subjects: Adipose Tissue/metabolism, Male, genetic association, subcutaneous fat, Transcription, Genetic, Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Mass Index, Continental Population Groups, Epigenesis, Genetic, Europe, Female, Genome, Human, Humans, Insulin, Insulin Resistance, Models, Biological, Neovascularization, Physiologic, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Characteristics, Waist-Hip Ratio, Body Fat Distribution, Genome-Wide Association Study, Multidisciplinary, Insulin Resistance/genetics, Genome-wide association study, Continental Population Groups/genetics, genetic analysis, heritability, gene cluster, Science::Biological sciences::Human anatomy and physiology [DRNTU], 0302 clinical medicine, high density lipoprotein cholesterol, Models, genetics [Insulin Resistance], histone modification, Age Factor, insulin receptor, 0303 health sciences, Adipocyte, Human/genetics, CARDIOGRAMplusC4D Consortium, ADIPOGENIC DIFFERENTIATION, genetic correlation, body fat, Continental Population Group, priority journal, 5 trisphosphate 3 phosphatase, GEFOS Consortium, meta analysis (topic), Science & Technology - Other Topics, ddc:500, transcription regulation, Adipogenesis/genetics, Single Nucleotide/genetics, Human, medicine.medical_specialty, Waist, phosphatidylinositol 3, European, ta3111, genetic regulation, Article, developmental biology, 03 medical and health sciences, MAGIC Investigators, transcription initiation site, SDG 3 - Good Health and Well-being, Genetic, genomics, GLYCEMIC TRAITS, genetics [Continental Population Groups], Polymorphism, GENOME-WIDE ASSOCIATION, Physiologic, genetics [Adipogenesis], Adipocytes/metabolism, Europe/ethnology, Genome, Human/genetics, Insulin/metabolism, Neovascularization, Physiologic/genetics, Obesity/genetics, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Transcription, Genetic/genetics, Genetic/genetics, Adipogenesi, Science & Technology, adiponectin, [ SDV ] Life Sciences [q-bio], vasculotropin, genetics [Quantitative Trait Loci], ta1184, Racial Groups, ta1182, gene mapping, ta3121, triacylglycerol blood level, medicine.disease, Biological, major clinical study, amino acid sequence, metabolism [Insulin], Endocrinology, metabolism [Adipocytes], genetic loci, insulin, body fat, GLGC, International Endogene Consortium, metabolism [Adipose Tissue], Body mass index, HUMAN HEIGHT, Epigenesis, LifeLines Cohort Study, ReproGen Consortium, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, tissue level, Physiologic/genetics, [SDV]Life Sciences [q-bio], Medizin, Adipose tissue, low density lipoprotein cholesterol, PAGE Consortium, COMMON SNPS, angiogenesis, Waist–hip ratio, genetics [Obesity], MESH: Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, single nucleotide polymorphism, fat, genetic variability, molecular biology, body mass index (BMI), ethnology [Europe], peroxisome proliferator activated receptor, 2. Zero hunger, Genetics, Genome, Single Nucleotide, waist circumference, insulin, phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase, triacylglycerol, vasculotropin, developmental biology, gene expression, genome, numerical model, adipocyte, adipose tissue, body fat distribution, body mass, female, gene locus, gene structure, hip circumference, human, insulin resistance, lipoprotein blood level, male, obesity, protein protein interaction, sex difference, waist hip ratio, Multidisciplinary Sciences, genetics [Transcription, Genetic], genetics [Polymorphism, Single Nucleotide], ADIPOGen Consortium, genetics [Neovascularization, Physiologic], Transcription, SUSCEPTIBILITY LOCI, General Science & Technology, ICBP, 030209 endocrinology & metabolism, Biology, adipocyte, MESH : Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, MESENCHYMAL STEM-CELLS, GENIE Consortium, SEXUAL-DIMORPHISM, Insulin resistance, Internal medicine, medicine, genetics [Genome, Human], ABDOMINAL ADIPOSITY, Neovascularization, 030304 developmental biology, FALSE DISCOVERY, CKDGen Consortium, Sex Characteristic, MuTHER Consortium, numerical model
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P
Published: 2015
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40. DataSHIELD: Taking the analysis to the data, not the data to the analysis

Author: Kirsti Kvaløy, Joel T. Minion, Chris Dibben, Isabel Fortier, Kim W. Carter, Gillian M. Raab, Ronald P. Stolk, Paul Burton, Mathieu Boniol, Susan E. Wallace, Catherine M. Phillips, Kristian Hveem, Chris Newby, Elinor Jones, Ivan J. Perry, Maria Bota, Richard W. Francis, Seán R. Millar, Oliver Butters, Julia Isaeva, Paolo Boffetta, Nuala A. Sheehan, Andrew Turner, Isabelle Budin-Ljøsne, Lisette Giepmans, Frank Popham, Andy Boyd, John Macleod, Bruce H R Woffenbuttel, Ipek Demir, Bartha Maria Knoppers, Carsten Oliver Schmidt, Eva Reischl, Barnaby Murtagh, Vincent Ferretti, Marja-Liisa Nuotio, Melanie Waldenberger, Philippe Laflamme, Yannick Marcon, Markus Perola, Edwin R. van den Heuvel, Jennifer R. Harris, Madeleine J Murtagh, Tero Hiekkalinna, N. Deklerk, Annette Peters, Amadou Gaye, Rebecca Wilson, Dany Doiron, Institute for Molecular Medicine Finland, Quantitative Genetics, Gaye, A., Marcon, Y., Isaeva, J., Laflamme, P., Turner, A., Jones, E.M., Minion, J., Boyd, A.W., Newby, C.J., Nuotio, M., Wilson, R., Butters, O., Murtagh, B., Demir, I., Doiron, D., Giepmans, L., Wallace, S.E., Budin-ljøsne, I., Oliver schmidt, C., Boffetta, P., Boniol, M., Bota, M., Carter, K.W., Deklerk, N., Dibben, C., Francis, R.W., Hiekkalinna, T., Hveem, K., Kvaløy, K., Millar, S., Perry, I.J., Peters, A., Phillips, C.M., Popham, F., Raab, G., Reischl, E., Sheehan, N., Waldenberger, M., Perola, M., Van den heuvel, E., Macleod, J., Knoppers, B.M., Stolk, R.P., Fortier, I., Harris, J.R., Woffenbuttel, B.H.R., Murtagh, M.J., Ferretti, V., Burton, P.R., Life Course Epidemiology (LCE), Lifestyle Medicine (LM), School of Social and Community Medicine [Bristol], University of Bristol [Bristol], McGill University Health Center [Montreal] (MUHC), Norwegian Institute of Public Health [Oslo] (NIPH), Department of Statistical Science, University College of London, University College of London [London] (UCL), Department of Infection, Immunity and Inflammation, Health Sciences, University of Leiceste, Institute for Molecular Medicine Finland (FIMM), Department of Chronic Disease Prevention, Unit of Public Health Genomics, National Institute for Health and Welfare [Helsinki], Department of Health Sciences [Leicester], University of Leicester, Department of Sociology [Leicester], Department of Epidemiology, University Medical Center Groningen, University of Groningen [Groningen], Greifswald University Hospital, International Prevention Research Institute (IPRI), The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai [New York] (MSSM), The University of Western Australia (UWA), School of Geosciences [Edinburgh], University of Edinburgh, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), HRB Centre for Diet and Health Research, Department of Epidemiology and Public Health, University College Cork, Research Unit of Molecular Epidemiology, Research Center for Environmental Health, MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, University of Tartu, University Medical Center Groningen, Medical Statistic, Centre of Genomics and Policy [Montréal] (CGP), McGill University = Université McGill [Montréal, Canada], University Medical Center Groningen, LifeLines Cohort Study, Department of Endocrinology, University Medical Center Groningen, Ontario Institute for Cancer Research [Canada] (OICR), and Ontario Institute for Cancer Research
Subjects: Biomedical Research, Datashield, Elsi, Bioinformatics, Confidentiality, Disclosure, Distributed Computing, Intellectual Property, Pooled Analysis, Privacy, Databases, Factual, Epidemiology, Pooling, Datasets as Topic, Information Storage and Retrieval, DISEASE, Firewall (construction), Medicine, pooled analysi, Biomedical Research Computational Biology *Computer Security *Confidentiality Databases, Data processing, PRIVACY, Intellectual property, General Medicine, bioinformatics, confidentiality, 3142 Public health care science, environmental and occupational health, 3. Good health, ELSI, INDIVIDUAL-LEVEL, pooled analysis, disclosure, Data Matters, education, MODELS, EPIDEMIOLOGIC RESEARCH, Pooled analysis, RS, distributed computing, DataSHIELD, Humans, QUALITY, GENOME-WIDE ASSOCIATION, Computer Security, METAANALYSIS, Data collection, bioinformatic, business.industry, DATASHAPER APPROACH, Computational Biology, intellectual property, Factual *Datasets as Topic Great Britain Humans *Information Storage and Retrieval DataSHIELD Elsi bioinformatics confidentiality disclosure distributed computing intellectual property pooled analysis privacy, Data science, United Kingdom, Distributed computing, Data set, Data access, COHORT PROFILE, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Gaye, Amadou Marcon, Yannick Isaeva, Julia LaFlamme, Philippe Turner, Andrew Jones, Elinor M Minion, Joel Boyd, Andrew W Newby, Christopher J Nuotio, Marja-Liisa Wilson, Rebecca Butters, Oliver Murtagh, Barnaby Demir, Ipek Doiron, Dany Giepmans, Lisette Wallace, Susan E Budin-Ljosne, Isabelle Oliver Schmidt, Carsten Boffetta, Paolo Boniol, Mathieu Bota, Maria Carter, Kim W deKlerk, Nick Dibben, Chris Francis, Richard W Hiekkalinna, Tero Hveem, Kristian Kvaloy, Kirsti Millar, Sean Perry, Ivan J Peters, Annette Phillips, Catherine M Popham, Frank Raab, Gillian Reischl, Eva Sheehan, Nuala Waldenberger, Melanie Perola, Markus van den Heuvel, Edwin Macleod, John Knoppers, Bartha M Stolk, Ronald P Fortier, Isabel Harris, Jennifer R Woffenbuttel, Bruce H R Murtagh, Madeleine J Ferretti, Vincent Burton, Paul R eng MC_UP_A540₁021/Medical Research Council/United Kingdom MR/K006525/1/Medical Research Council/United Kingdom Medical Research Council/United Kingdom Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't England 2014/09/30 06:00 Int J Epidemiol. 2014 Dec;43(6):1929-44. doi: 10.1093/ije/dyu188. Epub 2014 Sep 26.; International audience; BACKGROUND: Research in modern biomedicine and social science requires sample sizes so large that they can often only be achieved through a pooled co-analysis of data from several studies. But the pooling of information from individuals in a central database that may be queried by researchers raises important ethico-legal questions and can be controversial. In the UK this has been highlighted by recent debate and controversy relating to the UK's proposed 'care.data' initiative, and these issues reflect important societal and professional concerns about privacy, confidentiality and intellectual property. DataSHIELD provides a novel technological solution that can circumvent some of the most basic challenges in facilitating the access of researchers and other healthcare professionals to individual-level data. METHODS: Commands are sent from a central analysis computer (AC) to several data computers (DCs) storing the data to be co-analysed. The data sets are analysed simultaneously but in parallel. The separate parallelized analyses are linked by non-disclosive summary statistics and commands transmitted back and forth between the DCs and the AC. This paper describes the technical implementation of DataSHIELD using a modified R statistical environment linked to an Opal database deployed behind the computer firewall of each DC. Analysis is controlled through a standard R environment at the AC. RESULTS: Based on this Opal/R implementation, DataSHIELD is currently used by the Healthy Obese Project and the Environmental Core Project (BioSHaRE-EU) for the federated analysis of 10 data sets across eight European countries, and this illustrates the opportunities and challenges presented by the DataSHIELD approach. CONCLUSIONS: DataSHIELD facilitates important research in settings where: (i) a co-analysis of individual-level data from several studies is scientifically necessary but governance restrictions prohibit the release or sharing of some of the required data, and/or render data access unacceptably slow; (ii) a research group (e.g. in a developing nation) is particularly vulnerable to loss of intellectual property-the researchers want to fully share the information held in their data with national and international collaborators, but do not wish to hand over the physical data themselves; and (iii) a data set is to be included in an individual-level co-analysis but the physical size of the data precludes direct transfer to a new site for analysis.
Published: 2014
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41. Osteosarcopenia in Finland: prevalence and associated factors.

Author: Blomqvist M, Nuotio M, Sääksjärvi K, Koskinen S, and Stenholm S
Subjects: Humans, Male, Female, Finland epidemiology, Aged, Cross-Sectional Studies, Middle Aged, Prevalence, Risk Factors, Aged, 80 and over, Bone Density, Activities of Daily Living, Hand Strength, Sarcopenia epidemiology, Osteoporosis epidemiology
Abstract: This cross-sectional study investigated osteosarcopenia prevalence and its correlates among 2142 adults aged 55 and older in Finland. Findings show 3.9% had osteosarcopenia, while 13.8% and 11.1% had probable sarcopenia only or osteoporosis only, respectively. Osteosarcopenia was associated with low BMI, impaired mobility, ADL limitations and depression. Sarcopenia appeared to drive these associations more than osteoporosis. Osteosarcopenia may be a risk factor for functional decline, hospitalization, and institutionalization, warranting further research., Purpose: Osteosarcopenia is a disorder consisting of concurrent osteoporosis and sarcopenia. This cross-sectional study using nationally representative data from Finland in 2000 aimed to determine the prevalence of osteosarcopenia in Finland. In addition, associations of sociodemographic, lifestyle, anthropometric, physical and mental function indicators, chronic conditions and various biomarkers with osteosarcopenia were examined., Methods: The study included 2142 subjects aged 55 and over (mean age 68.0 years, SD 9.0). Probable sarcopenia was defined as grip strength < 27 kg for men and < 16 kg for women. Osteoporosis was defined as either ultrasound-based bone density measurement of T < -2.5, or self-reported, pre-existing diagnosis of osteoporosis. Participants were categorized into 4 groups: no sarcopenia and no osteoporosis, probable sarcopenia only, osteoporosis only, and osteosarcopenia. Information on sociodemographic, lifestyle, anthropometric, physical and mental function indicators, chronic conditions and various biomarkers were collected via structured interview, questionnaires, clinical examination, and blood and urine samples., Results: The prevalence of probable sarcopenia, osteoporosis and osteosarcopenia was 13.8%, 11.1%, and 3.9%, respectively. Osteosarcopenia was associated with low BMI, slow gait speed, impaired mobility, impaired ability in the activities of daily living and depression. Of the two components, probable sarcopenia appeared to contribute to these associations more than osteoporosis., Conclusion: According to representative population-based study, about every fifth person with probable sarcopenia also has osteoporosis. Mobility and ADL limitations were more common among people with osteosarcopenia than those with osteoporosis or probable sarcopenia alone. Future studies are needed to examine osteosarcopenia as an independent risk factor for functional decline, hospitalization, and institutionalization., (© 2024. The Author(s).)
Published: 2024
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42. Sex Difference in the Case Fatality of Older Myocardial Infarction Patients.

Author: Kytö V, Nuotio M, and Rautava P
Subjects: Aged, Aged, 80 and over, Female, Hospitalization, Humans, Male, Proportional Hazards Models, Registries, Risk Factors, Sex Factors, Treatment Outcome, Myocardial Infarction epidemiology, Sex Characteristics
Abstract: Background: The female sex is associated with poorer outcomes after myocardial infarction (MI), although current evidence in older patients is limited and mixed. We sought to evaluate sex-based differences in outcome after MI in older patients., Method: Consecutive older (≥70 years) all-comer patients with out-of-hospital MI admitted to 20 hospitals in Finland between 2005 and 2014 were studied using national registries (n = 40 654, mean age 80 years, 50% women). The outcome of interest was death within 1 year after MI. Differences between sexes (age, baseline features, medication, comorbidities, revascularization, and treating hospital) were balanced by inverse probability weighting., Results: Adjusted all-cause case fatality was lower in women than in men at 30 days (16.0% vs 19.0%, respectively) and at 1 year (27.7% vs 32.4%, respectively) after MI (hazard ratio: 0.83; confidence interval [CI]: 0.80-0.86; p < .0001). Excess 1-year case fatality after MI compared to the corresponding general population was 22.1% (CI: 21.4%-22.8%) in women and 24.1% (CI: 23.4%-24.9%) in men. Women had a lower adjusted hazard of death after MI in subgroups of patients aged 70-79 years and ≥80 years, patients with and without ST elevation MI, revascularized and non-revascularized patients, patients with and without atrial fibrillation, and patients with and without diabetes. The sex difference in case fatality remained similar during the study period., Conclusions: Older women were found to have a lower hazard of death after an out-of-hospital MI when compared to older men with similar features and treatments. This finding was consistent in several subgroups., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.)
Published: 2022
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43. Sex Differences in Cardiovascular Outcomes of Older Adults After Myocardial Infarction.

Author: Kerola AM, Palomäki A, Rautava P, Nuotio M, and Kytö V
Subjects: Aged, Female, Finland, Humans, Male, Registries, Retrospective Studies, Sex Factors, Treatment Outcome, Health Status Disparities, Myocardial Infarction therapy
Abstract: Background Evidence on the impact of sex on prognoses after myocardial infarction (MI) among older adults is limited. We evaluated sex differences in long-term cardiovascular outcomes after MI in older adults. Methods and Results All patients with MI ≥70 years admitted to 20 Finnish hospitals during a 10-year period and discharged alive were studied retrospectively using a combination of national registries (n=31 578, 51% men, mean age 79). The primary outcome was combined major adverse cardiovascular event within 10-year follow-up. Sex differences in baseline features were equalized using inverse probability weighting adjustment. Women were older, with different comorbidity profiles and rarer ST-segment-elevation MI and revascularization, compared with men. Adenosine diphosphate inhibitors, anticoagulation, statins, and high-dose statins were more frequently used by men, and renin-angiotensin-aldosterone inhibitors and beta blockers by women. After balancing these differences by inverse probability weighting, the cumulative 10-year incidence of major adverse cardiovascular events was 67.7% in men, 62.0% in women (hazard ratio [HR], 1.17; CI, 1.13-1.21; P <0.0001). New MI (37.0% in men, 33.1% in women; HR, 1.16; P <0.0001), ischemic stroke (21.1% versus 19.5%; HR, 1.10; P =0.004), and cardiovascular death (56.0% versus 51.1%; HR, 1.18; P <0.0001) were more frequent in men during long-term follow-up after MI. Sex differences in major adverse cardiovascular events were similar in subgroups of revascularized and non-revascularized patients, and in patients 70 to 79 and ≥80 years. Conclusions Older men had higher long-term risk of major adverse cardiovascular events after MI, compared with older women with similar baseline features and evidence-based medications. Our results highlight the importance of accounting for confounding factors when studying sex differences in cardiovascular outcomes.
Published: 2021
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44. European postgraduate curriculum in geriatric medicine developed using an international modified Delphi technique.

Author: Roller-Wirnsberger R, Masud T, Vassallo M, Zöbl M, Reiter R, Van Den Noortgate N, Petermans J, Petrov I, Topinkova E, Andersen-Ranberg K, Saks K, Nuotio M, Bonin-Guillaume S, Lüttje D, Mestheneos E, Szekacs B, Jonsdottir AB, O'Neill D, Cherubini A, Macijauskiene J, Leners JC, Fiorini A, van Iersel M, Ranhoff AH, Kostka T, Duque S, Prada GI, Davidovic M, Krajcik S, Kolsek M, Del Nozal JM, Ekdahl AW, Münzer T, Savas S, Knight P, Gordon A, and Singler K
Subjects: Aged, Curriculum, Delphi Technique, Education, Medical, Graduate methods, Education, Medical, Graduate standards, Europe, Geriatrics standards, Humans, Geriatrics education
Abstract: Background: the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations., Methods: under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators., Results: the final recommendations include four different domains: 'General Considerations' on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), 'Knowledge in patient care' (36 sub-items), 'Additional Skills and Attitude required for a Geriatrician' (9 sub-items) and a domain on 'Assessment of postgraduate education: which items are important for the transnational comparison process' (1 item)., Conclusion: the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states., (© The Author(s) (2019). Published by Oxford University Press on behalf of the British Geriatrics Society.)
Published: 2019
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45. Comparison of the Mini-Nutritional Assessment short and long form and serum albumin as prognostic indicators of hip fracture outcomes.

Author: Helminen H, Luukkaala T, Saarnio J, and Nuotio M
Subjects: Aged, Aged, 80 and over, Body Mass Index, Female, Finland epidemiology, Geriatric Assessment, Hip Fractures epidemiology, Hip Fractures metabolism, Humans, Independent Living, Male, Malnutrition diagnosis, Malnutrition epidemiology, Mobility Limitation, Nutrition Assessment, Nutrition Surveys, Perioperative Period, Postoperative Complications epidemiology, Prevalence, Prognosis, Prospective Studies, Risk Factors, Hip Fractures rehabilitation, Malnutrition metabolism, Postoperative Complications metabolism, Residence Characteristics statistics & numerical data, Serum Albumin metabolism
Abstract: Introduction: Malnutrition is common among older hip fracture patients and associated with adverse outcomes. We examined Mini Nutritional Assessment short (MNA-SF) and long form (MNA-LF) and serum albumin as prognostic indicators of mobility, living arrangements and mortality after hip fracture., Methods: Population-based prospective data were collected on 594 hip fracture patients aged 65 and over. MNA-SF, MNA-LF and serum albumin were assessed on admission. Outcomes were poorer mobility; transfer to more assisted living accommodation and mortality one month, four months and one year post fracture. Logistic regression analyses for mobility and living arrangements with odds ratios (OR) and Cox proportional hazards model for mortality with hazard ratios (HR) and 95% confidence intervals (CI) were used, adjusted for age, gender, ASA grade and fracture type., Results: All measures predicted mortality at all time-points. Risk of malnutrition and malnutrition measured by MNA-LF predicted mobility and living arrangements within four months of hip fracture. At one year, risk of malnutrition predicted mobility and malnutrition predicted living arrangements, when measured by MNA-LF. Malnutrition, but not risk thereof, measured by MNA-SF predicted living arrangements at all time-points. None of the measures predicted one-month mobility., Conclusions: All measures were strong indicators of short- and long-term mortality after hip fracture. MNA-LF was superior in predicting mobility and living arrangements, particularly at four months. All measures were relatively poor in predicting short-term outcomes of mobility and living arrangements., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
Published: 2017
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46. Does cognitive/physical screening in an outpatient setting predict institutionalization after hip fracture?

Author: Hongisto MT, Nuotio M, Luukkaala T, Väistö O, and Pihlajamäki HK
Subjects: Accidental Falls, Activities of Daily Living, Age Factors, Aged, Aged, 80 and over, Ambulatory Care methods, Cognition, Female, Hip Fractures economics, Homes for the Aged, Humans, Male, Prospective Studies, Risk Factors, Comprehensive Health Care methods, Geriatric Assessment methods, Health Services for the Aged, Hip Fractures therapy, Institutionalization, Neuropsychological Tests, Physical Examination
Abstract: Background: Institutionalization after hip fracture is a socio-economical burden. We examined the predictive value of Instrumental Activities of Daily Living (IADL) and Mini Mental State Examination (MMSE) for institutionalization after hip fracture to identify patients at risk for institutionalization., Methods: Fragility hip fracture patients ≥65 years of age (n = 584) were comprehensively examined at a geriatric outpatient clinic 4 to 6 months after surgery and followed 1 year postoperatively. A telephone interview with a structured inquiry was performed at 1, 4, and 12 months after hip fracture., Results: Age-adjusted univariate logistic regression analysis revealed that IADL and MMSE scores measured at the outpatient clinic were significantly associated with living arrangements 1 year after hip fracture. Multivariate logistic regression analysis established that institutionalization 1 year after hip fracture was significantly predicted by institutionalization at 4 months (odds ratio [OR] 16.26, 95 % confidence interval [CI] 7.37-35.86), IADL <5 (OR 12.96, 95 % CI 1.62-103.9), and MMSE <20 (OR 4.19, 95 % CI 1.82-9.66). A cut-off value of 5 was established for IADL with 100 % (95 % CI 96 %-100 %) sensitivity and 38 % (95 % CI 33 %-43 %) specificity and for MMSE, a cut-off value of 20 had 83 % (95 % CI 74 %-91 %) sensitivity and 65 % (95 % CI 60 %-70 %) specificity for institutionalization. During the time period from 4 to 12 months, 66 (11 %) patients changed living arrangements, and 36 (55 %) of these patients required more supportive accommodations., Conclusion: IADL and MMSE scores obtained 4 to 6 months after hospital discharge may be applicable for predicting institutionalization among fragility hip fracture patients ≥65 years of age at 1 year after hip fracture. An IADL score of ≥5 predicted the ability to remain in the community. Changes in living arrangements also often occur after 4 months.
Published: 2016
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47. Factors associated with changes in mobility and living arrangements in a comprehensive geriatric outpatient assessment after hip fracture.

Author: Nuotio M and Luukkaala T
Subjects: Aged, Aged, 80 and over, Comorbidity, Female, Finland, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Outpatients, Prospective Studies, Activities of Daily Living, Geriatric Assessment methods, Hip Fractures rehabilitation, Memory, Physical Therapy Modalities, Recovery of Function
Abstract: Purpose: To examine factors associated with changes in mobility and living arrangements in a comprehensive geriatric outpatient assessment after hip fracture., Method: Population-based prospective data on 887 consecutive hip fracture patients aged 65 years and older. The domains of the geriatric assessment were the independent and changes in mobility level and living arrangements 4 months postoperatively the outcome variables., Results: Of the survivors, 499 (73%) attended the assessment. The mobility level had declined in 39% of the attendees and 38% of them had moved to more supported living arrangements 4 months after the hip fracture. In the age-adjusted univariate logistic regression analyses, almost all the domains of the comprehensive geriatric assessment were significantly associated with both outcomes. In the forward stepwise multivariate analysis, disability in activities of daily living, poor performance in Timed Up and Go and comorbidity as measured by the American Society of Anesthesiologists scores remained significantly associated with the outcomes., Conclusions: While comorbidity and disability in activities of daily living and mobility are the major indicators of poor outcomes of mobility and living arrangements after hip fracture, all the domains in the comprehensive geriatric assessment deserve attention during hip fracture care and rehabilitation., Implications for Rehabilitation: In almost half of the patients the mobility level and living arrangements had deteriorated 4 months after the hip fracture, suggesting an urgent need for more effective postoperative rehabilitation. Almost all the domains of the comprehensive geriatric assessment were associated with poor outcomes and require equal attention during the acute and postacute phases of hip fracture care and in the course of rehabilitation. A geriatric outpatient assessment a few months after the hip fracture provides a check-point for the outcomes and an opportunity to target interventions at different domains of the comprehensive assessment.
Published: 2016
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48. Surgical procedures in femoral neck fractures in Finland: a nationwide study between 1998 and 2011.

Author: Hongisto MT, Pihlajamäki H, Niemi S, Nuotio M, Kannus P, and Mattila VM
Subjects: Age Factors, Aged, Aged, 80 and over, Arthroplasty, Replacement, Hip trends, Evidence-Based Medicine trends, Female, Femoral Neck Fractures epidemiology, Finland epidemiology, Fracture Fixation, Internal trends, Hemiarthroplasty trends, Humans, Incidence, Male, Middle Aged, Practice Guidelines as Topic, Retrospective Studies, Sex Factors, Arthroplasty, Replacement, Hip statistics & numerical data, Bone Cements, Femoral Neck Fractures surgery, Fracture Fixation, Internal statistics & numerical data, Hemiarthroplasty statistics & numerical data
Abstract: Purpose: For femoral neck fractures, recent scientific evidence supports cemented hemiarthroplasty (HA) over uncemented HA and suggests that total hip arthroplasty (THA) should be performed more frequently. We report the current surgical trends in treating femoral neck fractures in Finland., Methods: The study was conducted using the Finnish National Hospital Discharge Register and included all Finns at least 50 years of age who underwent surgery for femoral neck fractures from 1998 through 2011. Age- and sex-specific incidence rates and annual proportion of each treatment method were calculated., Results: During 1998-2011, a total of 49,514 operations for femoral neck fracture were performed in Finland. The proportion of uncemented HA increased from 8.1% in 2005 to 22.2% in 2011. During the same time, the proportion of cemented HA decreased from 63.9 to 52.5%, internal fixation decreased from 23.2 to 16.1% and THA increased from 4.9 to 9.2%., Conclusions: Between 2005 and 2011, the proportion of uncemented HA for femoral neck fractures increased markedly in Finland, while cemented HA and internal fixation declined. During this time, the use of THA nearly doubled. The current evidence-based guidelines for treatment of femoral neck fractures were mainly followed, but the increase in uncemented HA procedures contradicts recent scientific evidence.
Published: 2014
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49. Six-year follow-up and predictors of urgency-associated urinary incontinence and bowel symptoms among the oldest old: a population-based study.

Author: Nuotio M, Luukkaala T, Tammela TLJ, and Jylhä M
Subjects: Activities of Daily Living, Age Factors, Aged, Aged, 80 and over, Constipation epidemiology, Constipation psychology, Depression complications, Depression epidemiology, Fecal Incontinence epidemiology, Fecal Incontinence psychology, Female, Finland epidemiology, Follow-Up Studies, Humans, Longitudinal Studies, Male, Prevalence, Proportional Hazards Models, Sex Factors, Survival Analysis, Urinary Incontinence, Urge epidemiology, Urinary Incontinence, Urge psychology, Aging, Constipation complications, Fecal Incontinence complications, Urinary Incontinence, Urge complications
Abstract: Urinary urgency with incontinence, and fecal incontinence and constipation were followed up over a 6-year period in 398 subjects aged 70 years and over at baseline. Age- and gender-adjusted and multivariate Cox proportional hazard models were used to examine the associations of urinary urgency and fecal incontinence and constipation with mortality, and logistic regression models to determine predictors of incident symptoms among the survivors. The proportion of incident cases of urinary urgency with incontinence, fecal incontinence and constipation in the 252 survivors were 17% (n=46), 9% (n=34) and 13% (n=36), respectively. Frequently reported urinary urgency (hazard ratio, HR=2.23; 95% confidence interval, CI=1.37-3.61) and frequently reported fecal incontinence (HR=4.99; CI=2.11-11.79) were associated with mortality when adjusted for age and gender only. In the multivariate analyses, comorbidity (odds ratio, OR=5.54; CI=2.03-15.14), depressive mood (OR=5.78; CI=1.35-24.79) and instrumental activities of daily living (IADL) disability (OR=4.18, CI=1.52-11.50) predicted incident urgency urinary incontinence. Comorbidity (OR=2.91; CI=1.09-7.77) predicted incident fecal incontinence, while no significant predictors were identified for the incident symptom of constipation. Comorbidities and disabilities explain the association of severe urinary and fecal incontinence with mortality.
Published: 2009
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50. [Not Available].

Author: Kiilholma P, Ala-Nissilä S, Airaksinen O, Aukee P, Kivelä A, Kujansuu E, Leppilahti M, Mäkinen S, Nilsson CG, Nuotio M, Parantainen A, Kristiina P, Ruutiainen J, Stach-Lempinen B, and Valpas A
Published: 2007

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