32 results on '"Laaksonen Marika"'
Search Results
2. Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.
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Moayyeri, Alireza, Hsu, Yi-Hsiang, Karasik, David, Estrada, Karol, Xiao, Su-Mei, Nielson, Carrie, Srikanth, Priya, Giroux, Sylvie, Wilson, Scott G, Zheng, Hou-Feng, Smith, Albert V, Pye, Stephen R, Leo, Paul J, Teumer, Alexander, Hwang, Joo-Yeon, Ohlsson, Claes, McGuigan, Fiona, Minster, Ryan L, Hayward, Caroline, Olmos, José M, Lyytikäinen, Leo-Pekka, Lewis, Joshua R, Swart, Karin MA, Masi, Laura, Oldmeadow, Chris, Holliday, Elizabeth G, Cheng, Sulin, van Schoor, Natasja M, Harvey, Nicholas C, Kruk, Marcin, del Greco M, Fabiola, Igl, Wilmar, Trummer, Olivia, Grigoriou, Efi, Luben, Robert, Liu, Ching-Ti, Zhou, Yanhua, Oei, Ling, Medina-Gomez, Carolina, Zmuda, Joseph, Tranah, Greg, Brown, Suzanne J, Williams, Frances M, Soranzo, Nicole, Jakobsdottir, Johanna, Siggeirsdottir, Kristin, Holliday, Kate L, Hannemann, Anke, Go, Min Jin, Garcia, Melissa, Polasek, Ozren, Laaksonen, Marika, Zhu, Kun, Enneman, Anke W, McEvoy, Mark, Peel, Roseanne, Sham, Pak Chung, Jaworski, Maciej, Johansson, Åsa, Hicks, Andrew A, Pludowski, Pawel, Scott, Rodney, Dhonukshe-Rutten, Rosalie AM, van der Velde, Nathalie, Kähönen, Mika, Viikari, Jorma S, Sievänen, Harri, Raitakari, Olli T, González-Macías, Jesús, Hernández, Jose L, Mellström, Dan, Ljunggren, Osten, Cho, Yoon Shin, Völker, Uwe, Nauck, Matthias, Homuth, Georg, Völzke, Henry, Haring, Robin, Brown, Matthew A, McCloskey, Eugene, Nicholson, Geoffrey C, Eastell, Richard, Eisman, John A, Jones, Graeme, Reid, Ian R, Dennison, Elaine M, Wark, John, Boonen, Steven, Vanderschueren, Dirk, Wu, Frederick CW, Aspelund, Thor, Richards, J Brent, Bauer, Doug, Hofman, Albert, Khaw, Kay-Tee, Dedoussis, George, Obermayer-Pietsch, Barbara, Gyllensten, Ulf, Pramstaller, Peter P, and Lorenc, Roman S
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Calcaneus ,Humans ,Osteoporosis ,Genetic Predisposition to Disease ,Ultrasonography ,Cohort Studies ,Bone Density ,Polymorphism ,Single Nucleotide ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Fractures ,Bone ,Genome-Wide Association Study ,Young Adult ,Human Genome ,Genetics ,Aging ,2.1 Biological and endogenous factors ,Aetiology ,Musculoskeletal ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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- 2014
3. Healthy and Unhealthy Food Consumption in Relation to Quality of Life among Finnish Female Municipal Employees: A Cross-Sectional Study
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Bergman, Elina, primary, Vepsäläinen, Henna, additional, Erkkola, Maijaliisa, additional, Laaksonen, Marika, additional, Kautiainen, Hannu, additional, Penttinen, Markus A., additional, Rautava, Päivi, additional, and Korhonen, Päivi E., additional
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- 2022
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4. The Relationship between Dietary Habits and Work Engagement among Female Finnish Municipal Employees
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Virtanen, Jenni, primary, Penttinen, Markus A., additional, Laaksonen, Marika, additional, Erkkola, Maijaliisa, additional, Vepsäläinen, Henna, additional, Kautiainen, Hannu, additional, and Korhonen, Päivi, additional
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- 2022
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5. The Association between Healthy Diet and Burnout Symptoms among Finnish Municipal Employees
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Penttinen, Markus A., primary, Virtanen, Jenni, additional, Laaksonen, Marika, additional, Erkkola, Maijaliisa, additional, Vepsäläinen, Henna, additional, Kautiainen, Hannu, additional, and Korhonen, Päivi, additional
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- 2021
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6. Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis: The Young Finns Study
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Hamal Mishra Binisha, Mishra P Pashupati, Raitoharju Emma, Marttila Saara, Mononen Nina, Sievänen Harri, Viikari Jorma, Juonala Markus, Laaksonen Marika, Hutri-Kähönen Nina, Kähönen Mika, T. Raitakari Olli, and Lehtimäki Terho
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mental disorders ,Osteoporosis, atherosclerosis, comorbidity, gene expression data, weighted co-expression network analysis, MANOVA, pathway analysis - Abstract
The research focuses on the co-morbidity study of atherosclerosis and osteoporosis.
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- 2020
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7. Opettajien työhyvinvointi Uuden opetussuunnitelman yhteys koettuun työhyvinvointiin
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Laaksonen, Marika, Lundell, Kia, Soveltavan kasvatustieteen ja opettajankoulutuksen osasto, School of Applied Educational Science and Teacher Education, Filosofinen tiedekunta, Soveltavan kasvatustieteen ja opettajankoulutuksen osasto, Philosophical faculty, School of Applied Educational Science and Teacher Education, Filosofinen tiedekunta, and Philosophical faculty
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education ,kasvatustiede - Published
- 2020
8. The effects of brain-friendly diet on cognitive performance (Brave study)
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Savenius, Iina, primary, Hongisto, Sanna-Maria, additional, Sibakov, Juhani, additional, Loponen, Jussi, additional, Diaz, Heli, additional, Fogelholm, Leila, additional, Pakarinen, Satu, additional, Lukander, Kristian, additional, and Laaksonen, Marika, additional
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- 2020
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9. The effects of a brain-friendly diet on metabolic and physiological parameters and cognitive performance (Brave study)
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Hongisto, Sanna-Maria, primary, Laaksonen, Marika, additional, Kanerva, Noora, additional, Koponen, Johanna, additional, Parkkinen, Juuso, additional, Tikkanen, Emmi, additional, Sibakov, Juhani, additional, Loponen, Jussi, additional, Diaz, Heli, additional, Fogelholm, Leila, additional, Rantala, Jukka, additional, and Lindholm, Harri, additional
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- 2020
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10. Supplementary Appendix for the article Childhood exposure to passive smoking and bone health in adulthood. The Cardiovascular Risk in Young Finns Study
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Juonala, Markus, Pitkänen, Niina, Tolonen, Sanna, Laaksonen, Marika, Sievänen, Harri, Jokinen, Eero, Laitinen, Tomi, Sabin, Matthew, Hutri-Kähönen, Nina, Lehtimäki, Terho, Taittonen, Leena, Jula, Antti, Britt-Marie Loo, Impivaara, Olli, Kähönen, Mika, Magnussen, Costan, Viikari, Jorma, and Raitakari, Olli T
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digestive system diseases - Abstract
Supplementary Appendix for the article Childhood exposure to passive smoking and bone health in adulthood. The Cardiovascular Risk in Young Finns Study
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- 2019
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11. Childhood Exposure to Passive Smoking and Bone Health in Adulthood: The Cardiovascular Risk in Young Finns Study
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Juonala, Markus, primary, Pitkänen, Niina, additional, Tolonen, Sanna, additional, Laaksonen, Marika, additional, Sievänen, Harri, additional, Jokinen, Eero, additional, Laitinen, Tomi, additional, Sabin, Matthew A, additional, Hutri-Kähönen, Nina, additional, Lehtimäki, Terho, additional, Taittonen, Leena, additional, Jula, Antti, additional, Loo, Britt-Marie, additional, Impivaara, Olli, additional, Kähönen, Mika, additional, Magnussen, Costan G, additional, Viikari, Jorma S A, additional, and Raitakari, Olli T, additional
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- 2019
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12. P2-26-02 - The effects of brain-friendly diet on cognitive performance (Brave study)
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Laaksonen, Marika
- Abstract
Introduction:Cognitive performance is related to lipid and glucose metabolism and metabolic activation that are regulated by diet. The Brave study has shown beneficial effects of brain-friendly diet (Brainfood) on metabolic health in office workers with elevated metabolic risk. We further examined the effects of Brainfood on cognitive performance. Materials and methods: We conducted a diet-switch, 4-week intervention study on 84 volunteers with elevated plasma LDL levels in pre-screening. During the control period participants continued their habitual eating pattern and were offered an optional lunch following western-type diet, and they did not receive nutritional guidance. In Brainfood period, lunch, snack and breakfast offering was optimised for the quality of carbohydrates and fat and the intake of salt and protein. Educated nutritionist instructed the participants to follow the Brainfood diet and regular meal pattern. Participants kept a 3-day food record at the end of control and Brainfood periods. For each participant, the 3-day food record was used to calculate changes in mean daily consumption frequency of brain-friendly and brain-unfriendly foods between control and Brainfood period.Cognitive control and flexibility, attention, inhibition, learning, and memory were measured with neuropsychological tests (Bourdon-Wiersma double task, Stroop Colour and Word Test, WMS-III: Letter-Number Sequencing, Rey Auditory Verbal Learning Test), and modern computer and mobile tests (Flexible Attention Test FAT, N-Back task and Task-switching task) before and after the Brainfood diet. Subjective vigilance was assessed with the Karolinska Sleepiness Scale (KSS), experienced task load and performance with the Nasa- TLX index, and morning vitality weekly with the visual analogue scale (VAS). Participants were divided into four subgroups according to the dietary changes. The changes in cognitive performance (control vs. Brainfood diet) were compared between these subgroups using analyses of variance and covariance. In addition, the changes in cognitive performance were modelled in relation to diet compliance (% of consumed lunhch meals).Results: 59% of the subjects increased brain-friendly foods and decreased brain-unfriendly foods during the Brainfood intervention. Higher compliance with Brainfood lunch improved performance time in Stroop Colours and Word test. Brainfood consumption was associated with morning vitality (VAS).Discussion:Brainfood diet may positively affect cognitive performance in office workers with elevated metabolic risk.
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- 2017
13. Does Bone Resorption Stimulate Periosteal Expansion? A Cross‐Sectional Analysis of β‐C‐telopeptides of Type I Collagen (CTX), Genetic Markers of the RANKL Pathway, and Periosteal Circumference as Measured by pQCT
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Kemp, John P, Sayers, Adrian, Paternoster, Lavinia, Evans, David M, Deere, Kevin, St Pourcain, Beate, Timpson, Nicholas J, Ring, Susan M, Lorentzon, Mattias, Lehtimäki, Terho, Eriksson, Joel, Kähönen, Mika, Raitakari, Olli, Laaksonen, Marika, Sievänen, Harri, Viikari, Jorma, Lyytikäinen, Leo‐Pekka, Smith, George Davey, Fraser, William D, Vandenput, Liesbeth, Ohlsson, Claes, and Tobias, Jon H
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Genetic Markers ,Male ,Adolescent ,RANK Ligand ,Original Articles ,BONE RESORPTION ,Collagen Type I ,PERIOSTEAL EXPANSION ,Cross-Sectional Studies ,Periosteum ,Humans ,Original Article ,Female ,CTX ,Tomography, X-Ray Computed ,pQCT - Abstract
We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β‐C‐telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMDC). CTX and mid‐tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (β = 0.19 [0.13, 0.24]) (coefficient = SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMDC (β = –0.46 [–0.52,–0.40]) and cortical thickness [β = –0.11 (–0.18, –0.03)]. CTX was positively related to bone strength as reflected by the strength‐strain index (SSI) (β = 0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single‐nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF‐κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p
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- 2014
14. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci
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Reppe, Sjur, Wang, Yunpeng, Thompson, Wesley K., McEvoy, Linda K., Schork, Andrew J., Zuber, Verena, LeBlanc, Marissa, Bettella, Francesco, Mills, Ian G., Desikan, Rahul S., Djurovic, Srdjan, Gautvik, Kaare M., Dale, Anders M., Andreassen, Ole A., Estrada, Karol, Styrkarsdottir, Unnur, Evangelou, Evangelos, Hsu, Yi Hsiang, 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., 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., 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, 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, 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, Nguyen, Tuan V., Nogues, Xavier, Patel, Millan S., Prezelj, Janez, Rose, Lynda M., Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V., Svensson, Olle, Trompet, Stella, Trummer, Olivia, Van Schoor, Natasja M., Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M., Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung Min, Kollia, Panagoula, 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, 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., Aulchenko, Yurii S., Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gómez, Carolina, Palsson, Stefan Th, Rotter, Jerome I., Sigurdsson, Gunnar, Van Meurs, Joyce B.J., Verlaan, Dominique, Williams, Frances M.K., Wood, Andrew R., Zhou, Yanhua, 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., Gudnason, Vilmundur, Hofman, Albert, Jackson, Rebecca D., Jones, Graeme, Jukema, J. Wouter, Khaw, Kay Tee, Lehtimäki, Terho, Liu, Yongmei, Lorentzon, Mattias, McCloskey, Eugene, 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, 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., 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, Brown, Matthew A., Stefansson, Kari, Uitterlinden, André G., Ralston, Stuart H., Ioannidis, John P.A., Kiel, Douglas P., Rivadeneira, Fernando, Epidemiology and Data Science, EMGO - Musculoskeletal health, and Internal medicine
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musculoskeletal diseases - Abstract
Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.
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- 2015
15. New genetic loci link adipose and insulin biology to body fat distribution
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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, 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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], Departments of Epidemiology and Nutrition, Harvard School of Public Health, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Department of Genetics, University of Groningen [Groningen], deCODE Genetics, deCODE genetics [Reykjavik], Pediatric Pulmonology, Allergology & Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Department of Nutrition-Dietetics, Harokopio University of Athens, Yale School of Medicine [New Haven, Connecticut] (YSM), National Heart and Lung Institute (NHLI), Imperial College London, Queensland Institute of Medical Research, Concord Hospital, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, 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, Dept. 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Greifswald - University of Greifswald, Interfaculty Institute for Genetics and Functional Genomics, 5 University Street, Centre for Paediatric Epidemiology and Biostatistics, University College of London [London] (UCL), MRC Centre for Epidemiology of Child Health, UCL Institute of Child Health, Unit for Molecular Epidemiology, Institute of Health Sciences and Biocenter Oulu, University of Oulu, Department of Epidemiology and Biostatistics, Department of Life Course and Services, National Institute for Health and Welfare [Helsinki], Department of Epidemiology and Public Health, Queen's University [Belfast] (QUB), Interdisciplinary Center of Clinical Research, Department of Physiology, University of Eastern Finland-Institute of Biomedicine, University of Hawai‘i [Mānoa] (UHM), Department of Clinical Chemistry, University of Tampere [Finland]-Tampere University Hospital, Chronic Disease Epidemiology and Prevention Unit, Université Laval [Québec] (ULaval), Centre for Bone and Arthritis Research, University of Gothenburg (GU)-Institute of Medicine, Interdisciplinary Center for Psychiatric Epidemiology, Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Department of Clinical Physiology, Turku University Hospital (TYKS), Brigham and Women's Hospital [Boston], Department of Chronic Disease Prevention, Department of Cardiovascular Sciences [Leicester], University of Leicester, Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Maastricht University [Maastricht], Institute of Social and Preventive Medicine, Lausanne University Hospital, Carl Gustav Carus University Hospital, Recherches en Psychopathologie, nouveaux symptômes et lien social (EA 4050), Université de Poitiers-Université de Brest (UBO)-Université Catholique de l'Ouest (UCO)-Université de Rennes 2 (UR2), Institut de biologie de Lille - UMS 3702 (IBL), 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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, Massachusetts General Hospital [Boston], Divisions of Genetics and Endocrinology and Program in Genomics, Boston Children's Hospital, Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Metabolic Disease Group, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Epidemiology Unit, Addenbrooke's Hospital-Medical Research Council (MRC), Framingham Heart Study, Boston University [Boston] (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, M, Van Der Harst, P, Veronesi, G, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Abecasis, G, Assimes, T, Berndt, S, Boehnke, M, Borecki, I, Deloukas, P, Franke, L, Frayling, T, Groop, L, Hunter, D, Kaplan, R, O'Connell, J, Qi, L, Schlessinger, D, Strachan, D, Stefansson, K, Van Duijn, C, Willer, C, Visscher, P, Yang, J, Hirschhorn, J, Zillikens, M, Mccarthy, M, Speliotes, E, North, K, Fox, C, Barroso, I, Franks, P, Ingelsson, E, Heid, I, Loos, R, Cupples, L, Lindgren, C, Mohlke, K, Dastani, Z, Timpson, N, Yuan, X, Henneman, P, Kizer, J, Lyytikainen, L, Fuchsberger, C, Small, K, Coassin, S, Lohman, K, Pankow, J, Uh, H, Wu, Y, Bidulescu, A, Rasmussen Torvik, L, Greenwood, C, Ladouceur, M, Grimsby, J, Manning, A, Mooser, V, Kapur, K, Frants, R, Willemsvan vanDijk, K, Willems, S, Psaty, B, Tracy, R, Brody, J, Chen, I, Viikari, J, Kähönen, M, Evans, D, St Pourcain, B, Sattar, N, Carlson, O, Egan, J, van Heemst, D, Kedenko, L, Nuotio, M, Loo, B, Kanaya, A, Haun, M, Klopp, N, Katsareli, E, Couper, D, Duncan, B, Kloppenburg, M, Borja, J, Musani, S, Guo, X, Semple, R, Teslovich, T, Allison, M, Redline, S, Buxbaum, S, Meulenbelt, I, Ballantyne, C, Hu, F, Paulweber, B, Florez, J, Smith, G, Siscovick, D, Kronenberg, F, van Duijn, C, Waterworth, D, Meigs, J, Dupuis, J, Richards, J, Willenborg, C, Thompson, J, Erdmann, J, Goldstein, B, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikäinen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, 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, Pattaro, C, Köttgen, A, Garnaas, M, Böger, C, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, 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, Mychaleckyj, J, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Beckmann, J, Dreisbach, A, Styrkarsdottir, U, Evangelou, E, Hsu, Y, Duncan, E, Ntzani, E, Oei, L, Albagha, O, Kemp, J, Koller, D, Minster, R, Vandenput, L, Willner, D, Xiao, S, Yerges Armstrong, L, Zheng, H, Alonso, N, Kammerer, C, Kaptoge, S, Leo, P, Wilson, S, Aalto, V, Alen, M, Aragaki, A, Center, J, Dailiana, Z, Duggan, D, Garcia Giralt, N, Giroux, S, Hocking, L, Husted, L, Jameson, K, Khusainova, R, Kim, G, Koromila, T, Kruk, M, Laaksonen, M, 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, Sambrook, P, Sham, P, Tylavsky, F, Econs, M, Kung, A, Reeve, J, Streeten, E, Karasik, D, Ralston, S, Ioannidis, J, Kiel, D, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Mäkinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkilä, O, Hietala, K, Kytö, J, Lahermo, P, Lehto, M, Österholm, A, Parkkonen, M, Pitkäniemi, J, Rosengård Bärlund, M, Saraheimo, M, Sarti, C, Söderlund, J, Soro Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Wadén, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Tregouet, D, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Möllsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Fraser, R, Freitag, D, Gurdasani, D, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Van den Herik, E, Volcik, K, Asiki, G, Been, L, Bolton, J, Bonnycastle, L, Burnett, M, Cesana, G, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Kastelein, J, Kim, E, Komulainen, P, Lin, S, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Stančáková, A, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Willemsen, G, Young, E, Bennett, F, Boomsma, D, Bovet, P, Chen, Y, Feranil, A, Freimer, N, Hsiung, C, Järvelin, M, Kesäniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Martin, N, Meneton, P, Moilanen, L, Njølstad, I, Price, J, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sõber, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjögren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Grässler, J, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Stanèáková, A, Raffel, L, Yao, J, Schwartz, S, Ikram, M, Longstreth W., J, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Morken, M, Laitinen, J, 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
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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
16. Does Bone Resorption Stimulate Periosteal Expansion? A Cross-Sectional Analysis of b-C-telopeptides of Type I Collagen ( CTX),Genetic Markers of the RANKL Pathway, and Periosteal Circumference as Measured by
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Kemp, John P., Sayers, Adrian, Paternoster, Lavinia, Evans, David M., Deere, Kevin, St Pourcain, Beate, Timpson, Nicholas J., Ring, Susan M., Lorentzon, Mattias, Lehtimaki, Terho, Eriksson, Joel, Kahonen, Mika, Raitakari, Olli, Laaksonen, Marika, Sievanen, Harri, Viikari, Jorma, Lyytikainen, Leo-Pekka, Smith, George Davey, Fraser, William D., Vandenput, Liesbeth, Ohlsson, Claes, Tobias, Jon H., and Department of Food and Nutrition
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FAT MASS ,OSTEOPOROTIC FRACTURES ,IMPUTED DATA ,education ,MINERAL DENSITY ,CHILDREN ,SEX ,3111 Biomedicine ,GENOME-WIDE ASSOCIATION ,METABOLISM ,OSTEOCALCIN ,METAANALYSIS - Published
- 2014
17. Associations of gene polymorphisms and nutrition with calcium homeostasis and bone mineral density : Studies on skeletal nutrigenetics
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Laaksonen, Marika, University of Helsinki, Faculty of Agriculture and Forestry, Department of Applied Chemistry and Microbiology, Helsingin yliopisto, maatalous-metsätieteellinen tiedekunta, soveltavan kemian ja mikrobiologian laitos, Helsingfors universitet, agrikultur-forstvetenskapliga fakulteten, institutionen för tillämpad kemi och mikrobiologi, Åkesson, Kristina, Lamberg-Allardt, Christel, and Mutanen, Marja
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ravitsemustiede - Abstract
Heredity explains a major part of the variation in calcium homeostasis and bone strength, and the susceptibility to osteoporosis is polygenetically regulated. Bone phenotype results from the interplay between lifestyle and genes, and several nutritional factors modulate bone health throughout life. Thus, nutrigenetics examining the genetic variation in nutrient intake and homeostatic control is an important research area in the etiology of osteoporosis. Despite continuing progress in the search for candidate genes for osteoporosis, the results thus far have been inconclusive. The main objective of this thesis was to investigate the associations of lactase, vitamin D receptor (VDR), calcium sensing receptor (CaSR) and parathyroid hormone (PTH) gene polymorphisms and lifestyle factors and their interactions with bone health in Finns at varying stages of the skeletal life span. Markers of calcium homeostasis and bone remodelling were measured from blood and urine samples. Bone strength was measured at peripheral and central bone sites. Lifestyle factors were assessed with questionnaires and interviews. Genetic lactase non-persistence (the C/C-13910 genotype) was associated with lower consumption of milk from childhood, predisposing females in particular to inadequate calcium intake. Consumption of low-lactose milk and milk products was shown to decrease the risk for inadequate calcium intake. In young adulthood, bone loss was more common in males than in females. Males with the lactase C/C-13910 genotype may be more susceptible to bone loss than males with the other lactase genotypes, although calcium intake predicts changes in bone mass more than the lactase genotype. The BsmI and FokI polymorphisms of the VDR gene were associated with bone mass in growing adolescents, but the associations weakened with age. In young adults, the A986S polymorphism of the calcium sensing receptor gene was associated with serum ionized calcium concentrations, and the BstBI polymorphism of the parathyroid gene was related to bone strength. The FokI polymorphism and sodium intake showed an interaction effect on urinary calcium excretion. A novel gene-gene interaction between the VDR FokI and PTH BstBI gene polymorphisms was found in the regulation of PTH secretion and urinary calcium excretion. Further research should be carried out with more number of Finns at varying stages of the skeletal life span and more detailed measurements of bone strength. Research should concern mechanisms by which genetic variants affect calcium homeostasis and bone strength, and the role of diet-gene and gene-gene interactions in the pathogenesis of osteoporosis. Perimä selittää suuren osan kalsiumin aineenvaihdunnassa ja luun vahvuudessa esiintyvästä vaihtelusta ja monet ravintotekijät vaikuttavat luuston hyvinvointiin. Ravinnon ja perimän yhteisvaikutuksia selvittävä nutrigenetiikka on uusi ja merkittävä tutkimusalue osteoporoosin etiologiassa. Nutrigenetiikan saavutusten myötä tulevaisuudessa voidaan mahdollisesti ehkäistä sairauksien puhkeaminen yksilöllisillä ravitsemussuosituksilla, mutta toistaiseksi tutkimustulokset ovat melko ristiriitaisia. Väitöskirjatyössä tutkittiin kalsiumin saantia ja aineenvaihduntaa säätelevissä perintötekijöissä esiintyvän normaalivaihtelun eli geenipolymorfioiden sekä elintapojen yhteyksiä ja yhteisvaikutuksia luuston terveyteen eri-ikäisillä suomalaisilla. Tutkittavilta mitattiin kalsiumin ja luun aineenvaihduntaa kuvaavia merkkiaineita veri- ja virtsanäytteistä sekä luun vahvuutta luuston eri osista. Luuston hyvinvointiin vaikuttavat elintavat kartoitettiin kyselylomakkeilla ja tutkimuskäyntien yhteydessä. Perinnöllinen laktoosi-intoleranssi oli yhteydessä vähäisempään maidon käyttöön lapsuudesta alkaen altistaen erityisesti naiset riittämättömälle kalsiumin saannille. Vähälaktoosisten maitojen ja maitovalmisteiden käyttö suojasi laktoosi-intolerantikkoja suosituksia niukemmalta kalsiumin saannilta. Nuorella aikuisiällä luumassan menetys oli miehillä naisia yleisempää, ja perinnöllisesti laktoosi-intolerantikot miehet saattavat olla alttiimpia luukadolle. Kalsiumin saanti selittää suomalaisväestössä luumassan muutoksia kuitenkin paremmin kuin laktaasigenotyyppi, jonka yhteys luun vahvuuteen on osoitettu muissa väestöissä. D-vitamiinireseptorin geenipolymorfioilla havaittiin yhteyksiä kasvuikäisten luumassaan, mutta iän myötä polymorfiavaihtelun ja luun vahvuuden välinen yhteys heikkeni. Nuorista aikuisista koostuvassa tutkimusaineistossa kalsiumia sitovan reseptorin geenipolymorfia oli yhteydessä verenkierron kalsiumpitoisuuteen, ja lisäkilpirauhashormonin geenipolymorfian havaittiin selittävän luun vahvuudessa esiintyvää vaihtelua. Lisäksi D-vitamiinireseptorin geenipolymorfia sääteli suolan saannin vaikutuksia kalsiumin eritykseen. D-vitamiinireseptorin ja lisäkilpirauhashormonin geenipolymorfioilla havaittiin yhteisvaikutus kalsiumin aineenvaihduntaan, mikä on aiemmin julkaisematon tutkimushavainto. Ravinnon ja geenien yhteisvaikutuksia luuston terveyteen tulisi selvittää laajemmilla eri-ikäistä suomalaisväestöä edustavilla otoksilla. Jatkotutkimuksissa luun vahvuutta tulisi mitata monipuolisemmin ja lisäksi pyrkiä selvittämään tarkemmin mekanismeja, joilla perimä säätelee kalsiumin aineenvaihduntaa ja luun vahvuutta.
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- 2008
18. Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure
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Paternoster, Lavinia, Lorentzon, Mattias, Lehtimaki, Terho, Eriksson, Joel, Kahonen, Mika, Raitakari, Olli, Laaksonen, Marika, Sievanen, Harri, Viikari, Jorma, Lyytikainen, Leo-Pekka, Mellstrom, Dan, Karlsson, Magnus, Ljunggren, Östen, Grundberg, Elin, Kemp, John P., Sayers, Adrian, Nethander, Maria, Evans, David M., Vandenput, Liesbeth, Tobias, Jon H., Ohlsson, Claes, Paternoster, Lavinia, Lorentzon, Mattias, Lehtimaki, Terho, Eriksson, Joel, Kahonen, Mika, Raitakari, Olli, Laaksonen, Marika, Sievanen, Harri, Viikari, Jorma, Lyytikainen, Leo-Pekka, Mellstrom, Dan, Karlsson, Magnus, Ljunggren, Östen, Grundberg, Elin, Kemp, John P., Sayers, Adrian, Nethander, Maria, Evans, David M., Vandenput, Liesbeth, Tobias, Jon H., and Ohlsson, Claes
- Abstract
Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878) followed by replication (n = 1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6x10(-14); LOC285735, rs271170, p = 2.7x10(-12); OPG, rs7839059, p = 1.2x10(-10); and ESR1/C6orf97, rs6909279, p = 1.1x10(-9)). The trabecular vBMD GWA meta-analysis (n = 2,500) followed by replication (n = 1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9x10(-9)). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60-0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, a
- Published
- 2013
- Full Text
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19. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
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Estrada, Karol, Styrkarsdottir, Unnur, Evangelou, Evangelos, Hsu, Yi-Hsiang, 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., 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., 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, Duggan, David J., Garcia, Melissa, Garcia-Giralt, Natalia, Giroux, Sylvie, Hallmans, Goran, Hocking, Lynne J., Husted, Lise Bjerre, Jameson, Karen A., Khusainova, Rita, Kim, Ghi Su, 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, Nguyen, Tuan V., Nogues, Xavier, Patel, Millan S., Prezelj, Janez, Rose, Lynda M., Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V., Svensson, Olle, Trompet, Stella, Trummer, Olivia, van Schoor, Natasja M., Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M., Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, Gonzalez-Macias, Jesus, Kahonen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Langdahl, Bente Lomholt, Leslie, William D., Lips, Paul, Ljunggren, Östen, Lorenc, Roman S., Marc, Janja, Mellstrom, Dan, Obermayer-Pietsch, Barbara, Olmos, Jose M., Pettersson-Kymmer, Ulrika, Reid, David M., Riancho, Jose A., Ridker, Paul M., Rousseau, Francois, Slagboom, P. Eline, Tang, Nelson L. S., Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, Maria T., Aulchenko, Yurii S., Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gomez, Carolina, 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., 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., Gudnason, Vilmundur, Hofman, Albert, Jackson, Rebecca D., Jones, Graeme, Jukema, J. Wouter, Khaw, Kay-Tee, Lehtimaki, Terho, Liu, Yongmei, Lorentzon, Mattias, McCloskey, Eugene, 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, 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., 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, Brown, Matthew A., Stefansson, Kari, Uitterlinden, Andre G., Ralston, Stuart H., Ioannidis, John P. A., Kiel, Douglas P., Rivadeneira, Fernando, Estrada, Karol, Styrkarsdottir, Unnur, Evangelou, Evangelos, Hsu, Yi-Hsiang, 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., 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., 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, Duggan, David J., Garcia, Melissa, Garcia-Giralt, Natalia, Giroux, Sylvie, Hallmans, Goran, Hocking, Lynne J., Husted, Lise Bjerre, Jameson, Karen A., Khusainova, Rita, Kim, Ghi Su, 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, Nguyen, Tuan V., Nogues, Xavier, Patel, Millan S., Prezelj, Janez, Rose, Lynda M., Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V., Svensson, Olle, Trompet, Stella, Trummer, Olivia, van Schoor, Natasja M., Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M., Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, Gonzalez-Macias, Jesus, Kahonen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Langdahl, Bente Lomholt, Leslie, William D., Lips, Paul, Ljunggren, Östen, Lorenc, Roman S., Marc, Janja, Mellstrom, Dan, Obermayer-Pietsch, Barbara, Olmos, Jose M., Pettersson-Kymmer, Ulrika, Reid, David M., Riancho, Jose A., Ridker, Paul M., Rousseau, Francois, Slagboom, P. Eline, Tang, Nelson L. S., Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, Maria T., Aulchenko, Yurii S., Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gomez, Carolina, 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., 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., Gudnason, Vilmundur, Hofman, Albert, Jackson, Rebecca D., Jones, Graeme, Jukema, J. Wouter, Khaw, Kay-Tee, Lehtimaki, Terho, Liu, Yongmei, Lorentzon, Mattias, McCloskey, Eugene, 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, 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., 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, Brown, Matthew A., Stefansson, Kari, Uitterlinden, Andre G., Ralston, Stuart H., Ioannidis, John P. A., Kiel, Douglas P., and Rivadeneira, Fernando
- Abstract
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 x 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 x 10(-4), Bonferroni corrected), of which six reached P < 5 x 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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- 2012
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20. WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk
- Author
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Zheng, Hou-Feng, Tobias, Jon H, Duncan, Emma, Evans, David M, Eriksson, Joel, Paternoster, Lavinia, Yerges-Armstrong, Laura M, Lehtimäki, Terho, Bergström, Ulrica, Kähönen, Mika, Leo, Paul J, Raitakari, Olli, Laaksonen, Marika, Nicholson, Geoffrey C, Viikari, Jorma, Ladouceur, Martin, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Rivadeneira, Fernando, Prince, Richard L, Sievanen, Harri, Leslie, William D, Mellström, Dan, Eisman, John A, Movérare-Skrtic, Sofia, Goltzman, David, Hanley, David A, Jones, Graeme, St Pourcain, Beate, Xiao, Yongjun, Timpson, Nicholas J, Smith, George Davey, Reid, Ian R, Ring, Susan M, Sambrook, Philip N, Karlsson, Magnus, Dennison, Elaine M, Kemp, John P, Danoy, Patrick, Sayers, Adrian, Wilson, Scott G, Nethander, Maria, McCloskey, Eugene, Vandenput, Liesbeth, Eastell, Richard, Liu, Jeff, Spector, Tim, Mitchell, Braxton D, Streeten, Elizabeth A, Brommage, Robert, Pettersson-Kymmer, Ulrika, Brown, Matthew A, Ohlsson, Claes, Richards, J Brent, Lorentzon, Mattias, Zheng, Hou-Feng, Tobias, Jon H, Duncan, Emma, Evans, David M, Eriksson, Joel, Paternoster, Lavinia, Yerges-Armstrong, Laura M, Lehtimäki, Terho, Bergström, Ulrica, Kähönen, Mika, Leo, Paul J, Raitakari, Olli, Laaksonen, Marika, Nicholson, Geoffrey C, Viikari, Jorma, Ladouceur, Martin, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Rivadeneira, Fernando, Prince, Richard L, Sievanen, Harri, Leslie, William D, Mellström, Dan, Eisman, John A, Movérare-Skrtic, Sofia, Goltzman, David, Hanley, David A, Jones, Graeme, St Pourcain, Beate, Xiao, Yongjun, Timpson, Nicholas J, Smith, George Davey, Reid, Ian R, Ring, Susan M, Sambrook, Philip N, Karlsson, Magnus, Dennison, Elaine M, Kemp, John P, Danoy, Patrick, Sayers, Adrian, Wilson, Scott G, Nethander, Maria, McCloskey, Eugene, Vandenput, Liesbeth, Eastell, Richard, Liu, Jeff, Spector, Tim, Mitchell, Braxton D, Streeten, Elizabeth A, Brommage, Robert, Pettersson-Kymmer, Ulrika, Brown, Matthew A, Ohlsson, Claes, Richards, J Brent, and Lorentzon, Mattias
- Abstract
We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)
- Published
- 2012
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21. WNT16 Influences Bone Mineral Density, Cortical Bone Thickness, Bone Strength, and Osteoporotic Fracture Risk
- Author
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University of Helsinki, Department of Applied Chemistry and Microbiology (-2009), Zheng, Hou-Feng, Tobias, Jon H., Duncan, Emma, Evans, David M., Eriksson, Joel, Paternoster, Lavinia, Yerges-Armstrong, Laura M., Lehtimaki, Terho, Bergstrom, Ulrica, Kahonen, Mika, Leo, Paul J., Raitakari, Olli, Laaksonen, Marika, Nicholson, Geoffrey C., Viikari, Jorma, Ladouceur, Martin, Lyytikainen, Leo-Pekka, Medina-Gomez, Carolina, Rivadeneira, Fernando, Prince, Richard L., Sievanen, Harri, Leslie, William D., Mellstrom, Dan, Eisman, John A., Moverare-Skrtic, Sofia, Goltzman, David, Hanley, David A., Jones, Graeme, Pourcain, Beate St., Xiao, Yongjun, Timpson, Nicholas J., Smith, George Davey, Reid, Ian R., Ring, Susan M., Sambrook, Philip N., Karlsson, Magnus, Dennison, Elaine M., Kemp, John P., Danoy, Patrick, Sayers, Adrian, Wilson, Scott G., Nethander, Maria, McCloskey, Eugene, Vandenput, Liesbeth, Eastell, Richard, Liu, Jeff, Spector, Tim, Mitchell, Braxton D., Streeten, Elizabeth A., Brommage, Robert, Pettersson-Kymmer, Ulrika, Brown, Matthew A., Ohlsson, Claes, Richards, J. Brent, Lorentzon, Mattias, University of Helsinki, Department of Applied Chemistry and Microbiology (-2009), Zheng, Hou-Feng, Tobias, Jon H., Duncan, Emma, Evans, David M., Eriksson, Joel, Paternoster, Lavinia, Yerges-Armstrong, Laura M., Lehtimaki, Terho, Bergstrom, Ulrica, Kahonen, Mika, Leo, Paul J., Raitakari, Olli, Laaksonen, Marika, Nicholson, Geoffrey C., Viikari, Jorma, Ladouceur, Martin, Lyytikainen, Leo-Pekka, Medina-Gomez, Carolina, Rivadeneira, Fernando, Prince, Richard L., Sievanen, Harri, Leslie, William D., Mellstrom, Dan, Eisman, John A., Moverare-Skrtic, Sofia, Goltzman, David, Hanley, David A., Jones, Graeme, Pourcain, Beate St., Xiao, Yongjun, Timpson, Nicholas J., Smith, George Davey, Reid, Ian R., Ring, Susan M., Sambrook, Philip N., Karlsson, Magnus, Dennison, Elaine M., Kemp, John P., Danoy, Patrick, Sayers, Adrian, Wilson, Scott G., Nethander, Maria, McCloskey, Eugene, Vandenput, Liesbeth, Eastell, Richard, Liu, Jeff, Spector, Tim, Mitchell, Braxton D., Streeten, Elizabeth A., Brommage, Robert, Pettersson-Kymmer, Ulrika, Brown, Matthew A., Ohlsson, Claes, Richards, J. Brent, and Lorentzon, Mattias
- Published
- 2012
22. Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure
- Author
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Paternoster, Lavinia, primary, Lorentzon, Mattias, additional, Lehtimäki, Terho, additional, Eriksson, Joel, additional, Kähönen, Mika, additional, Raitakari, Olli, additional, Laaksonen, Marika, additional, Sievänen, Harri, additional, Viikari, Jorma, additional, Lyytikäinen, Leo-Pekka, additional, Mellström, Dan, additional, Karlsson, Magnus, additional, Ljunggren, Östen, additional, Grundberg, Elin, additional, Kemp, John P., additional, Sayers, Adrian, additional, Nethander, Maria, additional, Evans, David M., additional, Vandenput, Liesbeth, additional, Tobias, Jon H., additional, and Ohlsson, Claes, additional
- Published
- 2013
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23. WNT16 Influences Bone Mineral Density, Cortical Bone Thickness, Bone Strength, and Osteoporotic Fracture Risk
- Author
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Zheng, Hou-Feng, primary, Tobias, Jon H., additional, Duncan, Emma, additional, Evans, David M., additional, Eriksson, Joel, additional, Paternoster, Lavinia, additional, Yerges-Armstrong, Laura M., additional, Lehtimäki, Terho, additional, Bergström, Ulrica, additional, Kähönen, Mika, additional, Leo, Paul J., additional, Raitakari, Olli, additional, Laaksonen, Marika, additional, Nicholson, Geoffrey C., additional, Viikari, Jorma, additional, Ladouceur, Martin, additional, Lyytikäinen, Leo-Pekka, additional, Medina-Gomez, Carolina, additional, Rivadeneira, Fernando, additional, Prince, Richard L., additional, Sievanen, Harri, additional, Leslie, William D., additional, Mellström, Dan, additional, Eisman, John A., additional, Movérare-Skrtic, Sofia, additional, Goltzman, David, additional, Hanley, David A., additional, Jones, Graeme, additional, St. Pourcain, Beate, additional, Xiao, Yongjun, additional, Timpson, Nicholas J., additional, Smith, George Davey, additional, Reid, Ian R., additional, Ring, Susan M., additional, Sambrook, Philip N., additional, Karlsson, Magnus, additional, Dennison, Elaine M., additional, Kemp, John P., additional, Danoy, Patrick, additional, Sayers, Adrian, additional, Wilson, Scott G., additional, Nethander, Maria, additional, McCloskey, Eugene, additional, Vandenput, Liesbeth, additional, Eastell, Richard, additional, Liu, Jeff, additional, Spector, Tim, additional, Mitchell, Braxton D., additional, Streeten, Elizabeth A., additional, Brommage, Robert, additional, Pettersson-Kymmer, Ulrika, additional, Brown, Matthew A., additional, Ohlsson, Claes, additional, Richards, J. Brent, additional, and Lorentzon, Mattias, additional
- Published
- 2012
- Full Text
- View/download PDF
24. Long-term dietary patterns and carotid artery intima media thickness: The Cardiovascular Risk in Young Finns Study
- Author
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Mikkilä, Vera, primary, Räsänen, Leena, additional, Laaksonen, Marika M. L., additional, Juonala, Markus, additional, Viikari, Jorma, additional, Pietinen, Pirjo, additional, and Raitakari, Olli T., additional
- Published
- 2009
- Full Text
- View/download PDF
25. Habitual high phosphorus intakes and foods with phosphate additives negatively affect serum parathyroid hormone concentration: a cross-sectional study on healthy premenopausal women
- Author
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Kemi, Virpi E, primary, Rita, Hannu J, additional, Kärkkäinen, Merja UM, additional, Viljakainen, Heli T, additional, Laaksonen, Marika M, additional, Outila, Terhi A, additional, and Lamberg-Allardt, Christel JE, additional
- Published
- 2009
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26. Low calcium:phosphorus ratio in habitual diets affects serum parathyroid hormone concentration and calcium metabolism in healthy women with adequate calcium intake
- Author
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Kemi, Virpi E., primary, Kärkkäinen, Merja U. M., additional, Rita, Hannu J., additional, Laaksonen, Marika M. L., additional, Outila, Terhi A., additional, and Lamberg-Allardt, Christel J. E., additional
- Published
- 2009
- Full Text
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27. Vitamin D deficiency and low bone status in adult female garment factory workers in Bangladesh
- Author
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Islam, Md Zahirul, primary, Shamim, Abu Ahmed, additional, Kemi, Virpi, additional, Nevanlinna, Antti, additional, Akhtaruzzaman, Mohammad, additional, Laaksonen, Marika, additional, Jehan, Atia H., additional, Jahan, Khurshid, additional, Khan, Habib Ullah, additional, and Lamberg-Allardt, Christel, additional
- Published
- 2008
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28. WNT16 Influences Bone Mineral Density, Cortical Bone Thickness, Bone Strength, and Osteoporotic Fracture Risk.
- Author
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Hou.-Feng Zheng, Tobias, Jon H., Duncan, Emma, Evans, David M., Eriksson, Joel, Paternoster, Lavinia, Yerges-Armstrong, Laura M., Lehtimâki, Terho, Bergström, Ulrica, Kähönen, Mika, Leo, Paul J., Raitakari, Olli, Laaksonen, Marika, Nicholson, Geoffrey C., Viikari, Jorma, Ladouceur, Martin, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Rivadeneira, Fernando, and Prince, Richard L.
- Subjects
HUMAN genetic variation ,BONE density ,SINGLE nucleotide polymorphisms ,OSTEOPOROSIS ,BONE fractures - Abstract
We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ,2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr.Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of 20.11 29 standard deviations [SD] per C allele, P = 6.2x10
-9 ). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly.Arg), 212 also had genome-wide significant association with forearm BMD (20.14 SD per C allele, P = 2.3x10-12 , and 20.16 SD per G 215 allele, P = 1.2x10-15 , respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide 29 significant increased risk of forearm fracture (OR = 1.33, P = 7.3x10-9 ), with genome-wide suggestive signals from the two 26 26 missense variants inWNT16 (rs2908004: OR = 1.22, P = 4.9x10-6 and rs2707466: OR = 1.22, P = 7.2x10-6 ).We next generated a 2/2 homozygous mouse with targeted disruption of Wnt16. Female Wnt16 mice had 27% (P,0.001) thinner cortical bones at 213 24 the femur midshaft, and bone strength measures were reduced between 43%--61% (6.5610-4 ) at both femur and tibia, compared with their wild-type littermates. Natural variation in humans and targeted disruption in mice demonstrate that WNT16 is an important determinant of CBT, BMD, bone strength, and risk of fracture. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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29. Genetic lactase non-persistence, consumption of milk products and intakes of milk nutrients in Finns from childhood to young adulthood.
- Author
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Laaksonen, Marika M. L., Mikkilä, Vera, Räsänen, Leena, Rontu, Riikka, Lehtimäki, Terho J., Viikari, Jorma S. A., and Raitakari, Olli T.
- Published
- 2010
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30. Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis in the Young Finns Study
- Author
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Mishra, Binisha H., Mishra, Pashupati P., Raitoharju, Emma, Marttila, Saara, Mononen, Nina, Sievänen, Harri, Viikari, Jorma, Juonala, Markus, Laaksonen, Marika, Hutri-Kähönen, Nina, Kähönen, Mika, Raitakari, Olli T., Lehtimäki, Terho, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Department of Paediatrics, and Department of Clinical Physiology and Nuclear Medicine
- Subjects
Adult ,Male ,Molecular biology ,Science ,Gene Expression ,Article ,Cohort Studies ,Bone Density ,Humans ,Life Style ,Finland ,Genome, Human ,Reproducibility of Results ,Middle Aged ,3126 Surgery, anesthesiology, intensive care, radiology ,Atherosclerosis ,3142 Public health care science, environmental and occupational health ,Computational biology and bioinformatics ,1182 Biochemistry, cell and molecular biology ,Osteoporosis ,Medicine ,Female ,Systems biology ,Biomarkers - Abstract
We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj) < 0.05) and another two had suggestively significant (p.adj < 0.25) joint association with the two diseases after adjusting for age, sex, body mass index, smoking habit, alcohol consumption, and physical activity. The three most significant member genes from the significant modules were NOSIP, GXYLT2, and TRIM63 (p.adj ≤ 0.18). Genes in the modules were enriched with biological processes that have separately been found to be involved in either bone metabolism or atherosclerosis. The gene modules and their most significant member genes identified in this study support the osteoporosis-atherosclerosis comorbidity hypothesis and can provide new joint biomarkers for both diseases and their dual prevention. publishedVersion
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31. Low calcium:phosphorus ratio in habitual diets affects serum parathyroid hormone concentration and calcium metabolism in healthy women with adequate calcium intake.
- Author
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Kemi VE, Kärkkäinen MU, Rita HJ, Laaksonen MM, Outila TA, and Lamberg-Allardt CJ
- Subjects
- Adult, Bone Density Conservation Agents administration & dosage, Bone Density Conservation Agents urine, Bone Resorption blood, Bone Resorption metabolism, Calcium administration & dosage, Calcium urine, Calcium, Dietary administration & dosage, Cross-Sectional Studies, Diet Records, Female, Homeostasis, Humans, Micronutrients, Minerals, Nutritional Status, Osteoporosis prevention & control, Phosphorus, Dietary administration & dosage, Phosphorus, Dietary metabolism, Reference Values, Bone Density Conservation Agents metabolism, Calcium metabolism, Calcium, Dietary metabolism, Diet adverse effects, Parathyroid Hormone blood, Phosphorus, Dietary adverse effects
- Abstract
Excessive dietary P intake alone can be deleterious to bone through increased parathyroid hormone (PTH) secretion, but adverse effects on bone increase when dietary Ca intake is low. In many countries, P intake is abundant, whereas Ca intake fails to meet recommendations; an optimal dietary Ca:P ratio is therefore difficult to achieve. Our objective was to investigate how habitual dietary Ca:P ratio affects serum PTH (S-PTH) concentration and other Ca metabolism markers in a population with generally adequate Ca intake. In this cross-sectional analysis of 147 healthy women aged 31-43 years, fasting blood samples and three separate 24-h urinary samples were collected. Participants kept a 4-d food record and were divided into quartiles according to their dietary Ca:P ratios. The 1st quartile with Ca:P molar ratio < or = 0.50 differed significantly from the 2nd (Ca:P molar ratio 0.51-0.57), 3rd (Ca:P molar ratio 0.58-0.64) and 4th (Ca:P molar ratio > or = 0.65) quartiles by interfering with Ca metabolism. In the 1st quartile, mean S-PTH concentration (P = 0.021) and mean urinary Ca (U-Ca) excretion were higher (P = 0.051) than in all other quartiles. These findings suggest that in habitual diets low Ca:P ratios may interfere with homoeostasis of Ca metabolism and increase bone resorption, as indicated by higher S-PTH and U-Ca levels. Because low habitual dietary Ca:P ratios are common in Western diets, more attention should be focused on decreasing excessively high dietary P intake and increasing Ca intake to the recommended level.
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- 2010
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32. Genetic lactase non-persistence, consumption of milk products and intakes of milk nutrients in Finns from childhood to young adulthood.
- Author
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Laaksonen MM, Mikkilä V, Räsänen L, Rontu R, Lehtimäki TJ, Viikari JS, and Raitakari OT
- Subjects
- Adolescent, Adult, Analysis of Variance, Animals, Calcium administration & dosage, Cardiovascular Diseases etiology, Child, Child, Preschool, Cross-Sectional Studies, Female, Finland, Genotype, Humans, Lactose administration & dosage, Male, Nutritional Requirements, Prospective Studies, Risk, Sex Distribution, White People genetics, Diet, Feeding Behavior, Lactase genetics, Lactose Intolerance genetics, Milk, Polymorphism, Genetic
- Abstract
Previous evidence suggests that the lactase gene C/T- 13910 polymorphism (rs4988235) is associated with avoidance of milk products and lower Ca intake. We examined whether the consumption of milk and milk products and the intakes of milk nutrients differ between the lactase genotypes from childhood to young adulthood. Subjects belong to the Cardiovascular Risk in Young Finns Study where the first cross-sectional surveys were conducted in 1980 (n 3596), with follow-up studies in 1983, 1986, 1989, 1992 and 2001 (n 2620). The same dietary questionnaire was used throughout the follow-up to collect data on habitual consumption of milk and milk products in all subjects, and daily nutrient intakes were assessed with 48 h dietary recalls in 50 % of the subjects. Subjects with the lactase non-persistence (C/C- 13910) genotype consumed less milk since childhood, but the consumption of other milk products did not differ between the genotypes. In adult females, the lactose content of milk products consumed was lower (P = 0.003), and in both sexes low-lactose and milk-free diets were more common in the C/C- 13910 genotype than in the other genotypes. Inadequate Ca intake was most common in females with the C/C- 13910 genotype as early as in childhood (15-63 %), but in males only in adulthood (24 %). In adult females, preference for low-lactose milk and milk products equalised the differences in Ca intake between the genotypes. Thus, in those with the C/C- 13910 genotype, preference for low-lactose milk and milk products may decrease the risk for inadequate Ca intake.
- Published
- 2009
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