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1. Milk for Skeletal Muscle Health and Sarcopenia in Older Adults: A Narrative Review

Author

Granic A, Hurst C, Dismore L, Aspray T, Stevenson E, Witham MD, Sayer AA, and Robinson S

Subjects
sarcopenia, muscle health, whole foods, milk, myoprotective properties, older adults., Geriatrics, RC952-954.6
Abstract

Antoneta Granic,1,2 Christopher Hurst,1,2,* Lorelle Dismore,3,* Terry Aspray,1,2,4 Emma Stevenson,5,6 Miles D Witham,1,2 Avan A Sayer,1,2 Sian Robinson1,2 1AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK; 2NIHR Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle Upon Tyne, UK; 3Northumbria Healthcare NHS Foundation Trust, Research and Development, North Tyneside General Hospital, North Shields, UK; 4Newcastle Upon Tyne Hospitals NHS Foundation Trust, Musculoskeletal Unit, Freeman Hospital, Newcastle Upon Tyne, UK; 5Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK; 6Human Nutrition Research Centre, Newcastle University, Newcastle Upon Tyne, UK*These authors contributed equally to this workCorrespondence: Sian RobinsonNIHR Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Biomedical Research Building, 3rd Floor, Campus for Ageing and Vitality, Newcastle Upon Tyne NE4 5PL, UKTel +44 (0) 1912081325Email sian.robinson@newcastle.ac.ukAbstract: Skeletal muscle aging manifests as a decline in muscle quantity and quality that accelerates with aging, increasing the risk of sarcopenia. Sarcopenia is characterized by a loss of muscle strength and mass, and contributes to adverse health outcomes in older adults. Intervention studies have shown that sarcopenia may be treated by higher protein intake in combination with resistance exercise (RE). In comparison, less is known about the role of whole protein-containing foods in preventing or treating sarcopenia. Liquid milk contains multiple nutrients and bioactive components that may be beneficial for muscle, including proteins for muscle anabolism that, alone or with RE, may have myoprotective properties. However, there is a lack of evidence about the role of milk and its effects on muscle aging. This narrative review considers evidence from three observational and eight intervention studies that used milk or fortified milk, with or without exercise, as an intervention to promote muscle health and function in older adults (aged 50– 99 years). The observational studies showed no association between higher habitual milk consumption and muscle-related outcomes. The results of intervention studies using fortified milk in relation to elements of sarcopenia were also negative, with further inconclusive results from the studies using a combination of (fortified) milk and exercise. Although milk contains nutrients that may be myoprotective, current evidence does not show beneficial effects of milk on muscle health in older adults. This could be due to high habitual protein intakes (> 1.0 g/kg BW/d) in study participants, differences in the type of milk (low-fat vs whole) and timing of milk consumption, length of interventions, as well as differences in the sarcopenia status of participants in trials. Adequately powered intervention studies of individuals likely to benefit are needed to test the effectiveness of a whole food approach, including milk, for healthy muscle aging.Keywords: sarcopenia, muscle health, whole foods, milk, myoprotective properties, older adults

Published
2020

4. Prevention and optimal management of sarcopenia: a review of combined exercise and nutrition interventions to improve muscle outcomes in older people

Author

Denison HJ, Cooper C, Sayer AA, and Robinson SM

Subjects
Sarcopenia, diet, exercise, intervention, Geriatrics, RC952-954.6
Abstract

Hayley J Denison,1 Cyrus Cooper,1,2 Avan Aihie Sayer,1,2 Sian M Robinson1,2 1MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK; 2National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK Abstract: The growing recognition of sarcopenia, the age-related loss of skeletal muscle mass and function, has highlighted the need to understand more about its etiology. Declines in muscle mass and strength are expected aspects of aging, but there is significant variability between individuals in rates of loss. Although some of these differences can be explained by fixed factors, such as sex, much of the remaining variation is unexplained. This has led to increasing interest in the influence of adult lifestyle, particularly in the effects of modifiable factors such as physical activity and diet, and in identifying intervention opportunities both to prevent and manage sarcopenia. A number of trials have examined the separate effects of increased exercise or dietary supplementation on muscle mass and physical performance of older adults, but less is known about the extent to which benefits of exercise training could be enhanced when these interventions are combined. In a comprehensive review of the literature, we consider 17 studies of older adults (≥65 years) in which combined nutrition and exercise interventions were used to increase muscle strength and/or mass, and achieve improvements in physical performance. The studies were diverse in terms of the participants included (nutritional status, degree of physical frailty), supplementation strategies (differences in nutrients, doses), exercise training (type, frequency), as well as design (duration, setting). The main message is that enhanced benefits of exercise training, when combined with dietary supplementation, have been shown in some trials – indicating potential for future interventions, but that existing evidence is inconsistent. Further studies are needed, particularly of exercise training combined with dietary strategies that increase intakes of a range of nutrients, as well as bioactive non-nutrients, to provide the evidence on which public health and clinical recommendations can be based. Keywords: sarcopenia, diet, exercise, intervention

Published
2015

5. Performance of the SarQoL quality of life tool in a UK population of older people with probable sarcopenia and implications for use in clinical trials: findings from the SarcNet registry

Author

Witham, MD, Heslop, P, Dodds, RM, Clegg, AP, Hope, SV, McDonald, C, Smithard, D, Storey, B, Tan, AL, Thornhill, A, and Sayer, AA

Subjects
Male, Clinical Trials as Topic, Sarcopenia, Hand Strength, Psychometrics, United Kingdom, B800, Quality of Life, Humans, Female, Registries, Geriatrics and Gerontology, W200, Aged
Abstract

Background The Sarcopenia Quality of Life (SarQoL) questionnaire is a disease-specific sarcopenia quality of life tool. We aimed to independently assess SarQoL with a particular focus on its suitability as a clinical trial outcome measure. Methods We analysed data from the UK Sarcopenia Network and Registry. Measures of physical performance and lean mass were collected at baseline. SarQoL and the Strength, Assistance, Rise, Climb - Falls (SARC-F) questionnaire (to assess functional ability) were collected at both baseline and six-month follow-up. Global changes in fitness and quality of life at 6 months were elicited on seven-point Likert scales. Internal consistency was assessed using Cronbach’s alpha. Responsiveness (Cohen’s d and Guyatt coefficients) and minimum clinically important differences were calculated for participants reporting slight improvement or worsening in their global scores. Concurrent validity was assessed by correlating baseline SarQoL scores with measures of physical performance and functional ability. Results We analysed data from 147 participants, 125 of whom underwent follow up assessment; mean age 78 years; 72 (49%) were women. Internal consistency was good; Cronbach’s alpha was 0.944 at baseline and 0.732 at telephone follow-up. Correlation between baseline and follow-up SarQoL was weak (r = 0.27; p = 0.03). The minimum clinically important improvement ranged from 5 to 21 points giving trial sample size estimates of 25–100 participants. SarQoL scores were moderately correlated with handgrip (r = 0.37; p r = − 0.45; p r = 0.48; p r = 0.48; p Conclusions SarQoL has acceptable performance in older UK participants with probable sarcopenia and is sufficiently responsive for use in clinical trials for sarcopenia.

Published
2022

6. Defining terms commonly used in sarcopenia research: a glossary proposed by the Global Leadership in Sarcopenia (GLIS) Steering Committee

Author

Cawthon, PM, Visser, M, Arai, H, Avila-Funes, JA, Barazzoni, R, Bhasin, S, Binder, E, Bruyere, O, Cederholm, T, Chen, L-K, Cooper, C, Duque, G, Fielding, RA, Guralnik, J, Kiel, DP, Kirk, B, Landi, F, Sayer, AA, Von Haehling, S, Woo, J, Cruz-Jentoft, AJ, Cawthon, PM, Visser, M, Arai, H, Avila-Funes, JA, Barazzoni, R, Bhasin, S, Binder, E, Bruyere, O, Cederholm, T, Chen, L-K, Cooper, C, Duque, G, Fielding, RA, Guralnik, J, Kiel, DP, Kirk, B, Landi, F, Sayer, AA, Von Haehling, S, Woo, J, and Cruz-Jentoft, AJ

Abstract

METHODS: The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings. RESULTS: Several terms that are commonly used in sarcopenia research are defined, including self-reported measures of function and ability; objective physical performance tests; and measures related to muscle function and size. CONCLUSION: As new methods and technologies are developed, these definitions may be expanded or refined over time. Our goal is to promote this common language to describe sarcopenia and its components in clinical and research settings in order to increase clinical awareness and research interest in this important condition. We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition.

Published
2022

11. Research with older people in a world with COVID-19: Identification of current and future priorities, challenges and opportunities

Author

Richardson, SJ, Carroll, CB, Close, J, Gordon, AL, O’Brien, J, Quinn, TJ, Rochester, L, Sayer, AA, Shenkin, SD, van der Velde, N, Woo, J, Witham, MD, Richardson, SJ, Carroll, CB, Close, J, Gordon, AL, O’Brien, J, Quinn, TJ, Rochester, L, Sayer, AA, Shenkin, SD, van der Velde, N, Woo, J, and Witham, MD

Abstract

Older people are disproportionately affected by the COVID-19 pandemic, which has had a profound impact on research as well as clinical service delivery. This commentary identifies key challenges and opportunities in continuing to conduct research with and for older people, both during and after the current pandemic. It shares opinions from responders to an international survey, a range of academic authors and opinions from specialist societies. Priorities in COVID-19 research include its specific presentation in older people, consequences for physical, cognitive and psychological health, treatments and vaccines, rehabilitation, supporting care homes more effectively, the impact of social distancing, lockdown policies and system reconfiguration to provide best health and social care for older people. COVID-19 research needs to be inclusive, particularly involving older people living with frailty, cognitive impairment or multimorbidity, and those living in care homes. Non-COVID-19 related research for older people remains of critical importance and must not be neglected in the rush to study the pandemic. Profound changes are required in the way that we design and deliver research for older people in a world where movement and face-to-face contact are restricted, but we also highlight new opportunities such as the ability to collaborate more widely and to design and deliver research efficiently at scale and speed.

Published
2020

13. Adult Lifetime Diet Quality and Physical Performance in Older Age: Findings from a British Birth Cohort

Author

Robinson, SM, Westbury, LD, Cooper, R, Kuh, D, Ward, K, Syddall, HE, Sayer, AA, Cooper, C, Robinson, SM, Westbury, LD, Cooper, R, Kuh, D, Ward, K, Syddall, HE, Sayer, AA, and Cooper, C

Abstract

© The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. Background: Current evidence that links "healthier" dietary patterns to better measured physical performance is mainly from older populations; little is known about the role of earlier diet. We examined adult diet quality in relation to physical performance at age 60-64 years. Methods Diet quality was defined using principal component analysis of dietary data collected at age 36, 43, 53, and 60-64. Throughout adulthood, diets of higher quality were characterized by higher consumption of fruit, vegetables, and wholegrain bread. Diet quality scores calculated at each age indicated compliance with this pattern. Physical performance was assessed using chair rise, timed-up-and-go, and standing balance tests at age 60-64. The analysis sample included 969 men and women. Results In gender-adjusted analyses, higher diet quality at each age was associated with better measured physical performance (all p <.01 for each test), although some associations were attenuated after adjustment for covariates. Diet quality scores were highly correlated in adulthood (0.44 ≤ r ≤ 0.67). However, conditional models showed that higher diet quality at age 60-64 (than expected from scores at younger ages), was associated with faster chair rise speed and with longer standing balance time (adjusted: 0.08 [95% CI: 0.02, 0.15] and 0.07 [0.01, 0.14] SD increase in chair rise speed and balance time, respectively, per SD increase in conditional diet quality; both p <.05). Conclusions Higher diet quality across adulthood is associated with better physical performance in older age. Current diet quality may be particularly important for physical performance, suggesting potential for improvements in diet in early older age.

Published
2018

14. Sleep disturbance and the older worker: findings from the Health and Employment after Fifty Study

Author

Palmer, KT, D'Angelo, S, Harris, EC, Linaker, C, Sayer, AA, Gale, CR, Evandrou, M, van Staa, T, Cooper, C, and Coggon, D

Subjects
psychosocial, insomnia, older worker, occupational, sleep, Public aspects of medicine, RA1-1270, sleep disturbance, health and employment after fifty study
Abstract

Objectives: The aim of this study was to characterize the descriptive epidemiology of insomnia in midlife and explore the relative importance of different occupational risk factors for insomnia among older workers.Methods: A questionnaire was mailed to all adults aged 50–64 years registered with 24 English general practices. Insomnia was defined as having at least one of four problems with sleep severely in the past three months. Subjects were also asked about employment conditions, feelings concerning work, and their health. Associations were assessed by logistic regression and population attributable fractions (PAF) calculated.Results: Analysis was based on 8067 respondents (5470 in paid work), 18.8% of whom reported insomnia. It was more common among women, smokers, obese individuals, those living alone, and those in financial hardship, and less prevalent among the educated, those in South-East England, and those with friendships and leisure-time pursuits. Occupational risk factors included unemployment, shift working, lack of control and support at work, job insecurity, job dissatisfaction and several of its determinants (lacking a sense of achievement, feeling unappreciated, having difficult work colleagues, feeling unfairly criticized). Population burden of insomnia was associated more strongly with difficulties in coping with work demands, job insecurity, difficult colleagues, and lack of friendships at work [population attributable fraction (PAF) 15–33%] than shift work and lack of autonomy or support (PAF 5–7%). It was strongly associated with seven measures of poorer self-assessed health.Conclusions: Employment policies aimed at tackling insomnia among older workers may benefit from focusing particularly on job–person fit, job security and relationships in the workplace.

Published
2017

17. The feasibility and acceptability of muscle biopsy in epidemiological studies: Findings from the hertfordshire sarcopenia study (HSS)

Author

Patel, HP, Sayer, AA, Syddall, HE, Martin, HJ, Cooper, C, and Stewart, C

Abstract

Background: Sarcopenia, the loss of muscle mass and strength, is associated adversely with disability, morbidity and mortality. Epidemiological findings suggest influences operating across the life course may be important. Our aim was to ascertain the feasibility and acceptability of obtaining muscle tissue from healthy older people in order to ultimately identify cellular mechanisms underlying life course influences on sarcopenia. Methods: 105 men with documented birth weight consented to detailed assessment of muscle mass and strength, and a biopsy of the vastus lateralis using the Weil-Blakesley conchotome. Acceptability was ascertained by questionnaire and a 100mm pain Visual Analogue Scale (VAS). 100mm indicated severe pain. Results: Muscle biopsy was successfully carried out in 102 out of 105 participants, mean yield 107mg (range 20-290mg). There were no serious wound complications. Ninety-three participants completed feedback questionnaires. The median pain VAS score during the procedure was 7mm (Interquartile range [IQR] 1-34), 4mm (IQR 0-16) one day after the procedure and 1mm (IQR 0-4) 7 days after the procedure. 60 (65%) participants were back to their normal levels of activity one day after the procedure. 85 (91%) found this procedure acceptable and would have the procedure again. Conclusion: Muscle biopsy using a Weil-Blakesley conchotome is both feasible and acceptable in community dwelling older men participating in epidemiological research. The excellent yield of biopsy tissue will allow morphological and molecular studies of muscle to be integrated into an epidemiological study facilitating investigation of the mechanisms underpinning sarcopenia that could potentially be altered by life course influences. © 2010 Serdi and Springer Verlag France.

Published
2016

21. Associations between grip strength of parents and their 4-year-old children: Findings from the Southampton Women's Survey

Author

Inskip, H, Macdonald-Wallis, C, Kapasi, T, Robinson, S, Godfrey, K, Cooper, C, Harvey, N, and Sayer, AA

Abstract

Relationships between birthweight and grip strength throughout the life course suggest that early influences on the growth and development of muscle are important for long-term muscle function. However, little is known about parental influences on children's grip strength. We have explored this in the Southampton Women's Survey, a prospective general population cohort study from before conception through childhood. Grip strength was measured using a Jamar handgrip dynamometer in the mother at 19 weeks' gestation and her partner, and in the child at age 4 years. Pre-pregnancy heights and weights were measured in the mothers; reported weights and measured heights were available for the fathers. Complete data on parents and children were available for 444 trios. In univariable analyses, both parents' grip strengths were significantly associated with that of the child (r = 0.17, P < 0.001 for mothers; r = 0.15, P = 0.002 for fathers). These correlations were similar to that between the grip strength of the mothers and the fathers (r = 0.17, P < 0.001). In the multivariable model, after adjustment for child's height and physical activity, the correlations with the child's grip strength were attenuated, being 0.10 (P = 0.02) and 0.11 (P = 0.01) for mothers' and fathers' grip strength respectively. The findings show that grip strength of each parent is associated with that of the child, indicating that heritable influences and the shared family environment influence the development of muscle strength. This contributes to our understanding of the role of heritable and environmental factors on early muscle growth and development, which are important for muscle function across the life course.

Published
2016

22. Peri-implantation and late gestation maternal undernutrition differentially affect fetal sheep skeletal muscle development

Author

Costello, PM, Rowlerson, A, Astaman, NA, Anthony, FE, Sayer, AA, Cooper, C, Hanson, MA, and Green, LR

Abstract

Poor prenatal nutrition is associated with a greater risk of adult glucose intolerance and insulin insensitivity in the offspring. Skeletal muscle is the primary tissue for glucose utilization, and insulin resistance in muscle is the earliest identifiable abnormality in the pre-diabetic patient. We investigated the effect of early and late gestation undernutrition on structure and markers of growth and glucose metabolism regulation in the fetal triceps brachii (TB, slow- and fast-twitch myofibres) and soleus (slow-twitch myofibres) muscles. Pregnant sheep were fed 100% nutrient requirements (C, n = 8) or a restricted diet peri-implantation (PI, n = 9; 40%, 1-31 days gestation (dGA) (term approximately 147)) or in late gestation (L, n = 6; 50%, 104-127 dGA). At 127 +/- 1 dGA we measured myofibre and capillary density in the fetal TB and soleus muscles, and mRNA levels in the TB of insulin receptor (InsR), glucose transporter-4 (GLUT-4) and type 1 insulin-like growth factor receptor (IGF-1R). Total myofibre and capillary densities were lower in the TB, but not the soleus, of PI and L fetuses. The predominant effect in the L group was on slow-twitch myofibres. In TB, InsR, GLUT-4 and IGF-1R mRNA levels were greater in L group fetuses. Our finding of reduced myofibre density is consistent with a redistribution of resources at the expense of specific peripheral tissues by early and late gestation undernutrition which may be mediated by a decrease in capillary density. The increase in key regulatory components of glucose uptake following late gestation undernutrition may constitute a short-term compensation to maintain glucose homeostasis in the face of fewer type I (insulin-sensitive) myofibres. However, together these adaptations may influence the risk of later metabolic disease and thus our findings have implications for future strategies aimed at improving maternal diet.

Published
2016

28. Diet and its relationship with grip strength in community-dwelling older men and women: the Hertfordshire cohort study

Author

Robinson, SM, Jameson, KA, Batelaan, SF, Martin, HJ, Syddall, HE, Dennison, EM, Cooper, C, and Sayer, AA

Abstract

OBJECTIVES: To examine relationships between diet and grip strength in older men and women and to determine whether prenatal growth modifies these relationships. DESIGN: Cross-sectional and retrospective cohort study. SETTING: Hertfordshire, United Kingdom. PARTICIPANTS: Two thousand nine hundred eighty-three men and women aged 59 to 73 who were born and still living in Hertfordshire, United Kingdom. MEASUREMENTS: Weight at birth recorded in Health Visitor ledgers; current food and nutrient intake assessed using an administered food frequency questionnaire; and grip strength measured using a handheld dynamometer. RESULTS: Grip strength was positively associated with height and weight at birth and inversely related to age (all P

Published
2016

40. Reply [7]

Author

Sayer, AA, Briggs, R, Turner, G, Cooper, C, Syddall, H, and Kerr, A

Published
2016

44. Gender and telomere length:Systematic review and meta-analysis

Author

Gardner M, Bann D, Wiley L, Cooper R, Hardy R, Nitsch D, Martin Ruiz C, Shiels P, Sayer AA, BARBIERI, Michelangela, Bekaert S, Bischoff C, Brooks Wilson A, Chen W, Cooper C, Christensen K, De Meyer T, Deary I, Der G, Roux AD, Fitzpatrick A, Hajat A, Halaschek Wiener J, Harris S, Hunt SC, Jagger C, Jeon HS, Kaplan R, Kimura M, Lansdorp P, Li C, Maeda T, Mangino M, Nawrot TS, Nilsson P, Nordfjall K, Ren F, Riabowol K, Robertson T, Roos G, Staessen JA, Spector T, Tang N, Unryn B, van der Harst P, Woo J, Xing C, Yadegarfar ME, Park JY, Young N, Kuh D, vonZglinicki T, Ben Shlomo Y, the Halcyon study team, PAOLISSO, Giuseppe, Gardner, M, Bann, D, Wiley, L, Cooper, R, Hardy, R, Nitsch, D, Martin Ruiz, C, Shiels, P, Sayer, Aa, Barbieri, Michelangela, Bekaert, S, Bischoff, C, Brooks Wilson, A, Chen, W, Cooper, C, Christensen, K, De Meyer, T, Deary, I, Der, G, Roux, Ad, Fitzpatrick, A, Hajat, A, Halaschek Wiener, J, Harris, S, Hunt, Sc, Jagger, C, Jeon, H, Kaplan, R, Kimura, M, Lansdorp, P, Li, C, Maeda, T, Mangino, M, Nawrot, T, Nilsson, P, Nordfjall, K, Paolisso, Giuseppe, Ren, F, Riabowol, K, Robertson, T, Roos, G, Staessen, Ja, Spector, T, Tang, N, Unryn, B, van der Harst, P, Woo, J, Xing, C, Yadegarfar, Me, Park, Jy, Young, N, Kuh, D, Vonzglinicki, T, Ben Shlomo, Y, and the Halcyon study, Team

Published
2014

45. A study of common Mendelian disease carriers across ageing British cohorts:Meta-analyses reveal heterozygosity for alpha 1-antitrypsin deficiency increases respiratory capacity and height

Author

North, TL, Ben-Shlomo, Y, Cooper, C, Deary, IJ, Gallacher, J, Kivimaki, M, Kumari, M, Martin, RM, Pattie, A, Sayer, AA, Starr, JM, Wong, A, Kuh, D, Rodriguez, S, and Day, IN

Subjects
Male, Heterozygote, Polymorphism, Genetic, HALCion, Cystic Fibrosis, Genotype, Complex Traits, HMGA2 Protein, ALSPAC, respiratory system, respiratory tract diseases, Europe, Pulmonary Disease, Chronic Obstructive, Phenotype, Forced Expiratory Volume, Phenylketonurias, alpha 1-Antitrypsin, alpha 1-Antitrypsin Deficiency, Humans, Female, Alleles, Mendelian carriers, height
Abstract

BACKGROUND: Several recessive Mendelian disorders are common in Europeans, including cystic fibrosis (CFTR), medium-chain-acyl-Co-A-dehydrogenase deficiency (ACADM), phenylketonuria (PAH) and alpha 1-antitrypsin deficiency (SERPINA1).METHODS: In a multicohort study of >19 000 older individuals, we investigated the relevant phenotypes in heterozygotes for these genes: lung function (forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC)) for CFTR and SERPINA1; cognitive measures for ACADM and PAH; and physical capability for ACADM, PAH and SERPINA1.RESULTS: Findings were mostly negative but lung function in SERPINA1 (protease inhibitor (PI) Z allele, rs28929474) showed enhanced FEV1 and FVC (0.13 z-score increase in FEV1 (p=1.7×10(-5)) and 0.16 z-score increase in FVC (p=5.2×10(-8))) in PI-MZ individuals. Height adjustment (a known, strong correlate of FEV1 and FVC) revealed strong positive height associations of the Z allele (1.50 cm increase in height (p=3.6×10(-10))).CONCLUSIONS: The PI-MZ rare (2%) SNP effect is nearly four times greater than the 'top' common height SNP in HMGA2. However, height only partially attenuates the SERPINA1-FEV1 or FVC association (around 50%) and vice versa. Height SNP variants have recently been shown to be positively selected collectively in North versus South Europeans, while the Z allele high frequency is localised to North Europe. Although PI-ZZ is clinically disadvantageous to lung function, PI-MZ increases both height and respiratory function; potentially a balanced polymorphism. Partial blockade of PI could conceivably form part of a future poly-therapeutic approach in very short children. The notion that elastase inhibition should benefit patients with chronic obstructive pulmonary disease may also merit re-evaluation. PI is already a therapeutic target: our findings invite a reconsideration of the optimum level in respiratory care and novel pathway potential for development of agents for the management of growth disorders.

Published
2016

46. Global variation in grip strength: a systematic review and meta-analysis of normative data

Author

Cooper, Rachel, Dodds, RM, Syddall, HE, Cooper, R, Kuh, D, Cooper, C, and Sayer, AA

Abstract

Background: weak grip strength is a key component of sarcopenia and is associated with subsequent disability and mortality. We have recently established life course normative data for grip strength in Great Britain, but it is unclear whether the cut 209 Global variation in grip strength points we derived for weak grip strength are suitable for use in other settings. Our objective was to investigate differences in grip strength by world region using our data as a reference standard. Methods: we searched MEDLINE and EMBASE for reporting age- and gender-stratified normative data for grip strength. We extracted each item of normative data and converted it on to a Z-score scale relative to our British centiles. We performed meta-regression to pool the Z-scores and compare them by world region. Findings: our search returned 806 abstracts. Sixty papers met inclusion criteria and reported on 63 different samples. Seven UN regions were represented, although most samples (n = 44) were based in developed regions. We extracted 726 normative data items relating to 96,537 grip strength observations. Normative data from developed regions were broadly similar to our British centiles, with a pooled Z-score 0.12 SDs (95% CI: 0.07, 0.17) above the corresponding British centiles. By comparison, normative data from developing regions were clearly lower, with a pooled Z-score of −0.85 SDs (95% CI: −0.94, −0.76). Interpretation: our findings support the use of our British grip strength centiles and their associated cut points in consensus definitions for sarcopenia and frailty across developed regions, but highlight the need for different cut points in developing regions

Published
2016

47. Increased expression of H19/miR-675 is associated with a low fat free mass index in patients with COPD

Author

Lewis, A, Donaldson, AV, Natanek, SA, Vaidyanathan, S, Man, WDC, Hopkinson, NS, Sayer, AA, Patel, HP, Cooper, C, Syddall, H, Polkey, MI, Kemp, PR, Medical Research Council (MRC), and National Institute for Health Research

Subjects
Regeneration, Skeletal muscle, MiRNA, Cell proliferation
Abstract

© 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society of Sarcopenia, Cachexia and Wasting DisordersBackground: Loss of muscle mass and strength is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD) that limits their quality of life and has prognostic implications but does not affect everyone equally. To identify mechanisms that may contribute to the susceptibility to a low muscle mass, we investigated microRNA (miRNA) expression, methylation status, and regeneration in quadriceps muscle from COPD patients and the effect of miRNAs on myoblast proliferation in vitro. The relationships of miRNA expression with muscle mass and strength was also determined in a group of healthy older men. Methods: We identified miRNAs associated with a low fat-free mass (FFM) phenotype in a small group of patients with COPD using a PCR screen of 750 miRNAs. The expression of two differentially expressed miRNAs (miR-675 and miR-519a) was determined in an expanded group of COPD patients and their associations with FFM and strength identified. The association of these miRNAs with FFM and strength was also explored in a group of healthy community-dwelling older men. As the expression of the miRNAs associated with FFM could be regulated by methylation, the relative methylation of the H19 ICR was determined. Furthermore, the proportion of myofibres with centralized nuclei, as a marker of muscle regeneration, in the muscle of COPD patients was identified by immunofluorescence. Results: Imprinted miRNAs (miR-675 and from a cluster, C19MC which includes miR-519a) were differentially expressed in the quadriceps of patients with a low fat-free mass index (FFMI) compared to those with a normal FFMI. In larger cohorts, miR-675 and its host gene (H19) were higher in patients with a low FFMI and strength. The association of miR-519a expression with FFMI was present in male patients with severe COPD. Similar associations of miR expression with lean mass and strength were not observed in healthy community dwelling older men participating in the Hertfordshire Sarcopenia Study. Relative methylation of the H19 ICR was reduced in COPD patients with muscle weakness but was not associated with FFM. In vitro, miR-675 inhibited myoblast proliferation and patients with a low FFMI had fewer centralized nuclei suggesting miR-675 represses regeneration. Conclusions: The data suggest that increased expression of miR-675/H19 and altered methylation of the H19 imprinting control region are associated with a low FFMI in patients with COPD but not in healthy community dwelling older men suggesting that epigenetic control of this loci may contribute to a susceptibility to a low FFMI.

Published
2015

48. Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12

Author

Jackson, VE, Ntalla, I, Sayers, I, Morris, R, Whincup, P, Casas, J-P, Amuzu, A, Choi, M, Dale, C, Kumari, M, Engmann, J, Kalsheker, N, Chappell, S, Guetta-Baranes, T, McKeever, TM, Palmer, CNA, Tavendale, R, Holloway, JW, Sayer, AA, Dennison, EM, Cooper, C, Bafadhel, M, Barker, B, Brightling, C, Bolton, CE, John, ME, Parker, SG, Moffat, MF, Wardlaw, AJ, Connolly, MJ, Porteous, DJ, Smith, BH, Padmanabhan, S, Hocking, L, Stirrups, KE, Deloukas, P, Strachan, DP, Hall, IP, Tobin, MD, Wain, LV, Jackson, VE, Ntalla, I, Sayers, I, Morris, R, Whincup, P, Casas, J-P, Amuzu, A, Choi, M, Dale, C, Kumari, M, Engmann, J, Kalsheker, N, Chappell, S, Guetta-Baranes, T, McKeever, TM, Palmer, CNA, Tavendale, R, Holloway, JW, Sayer, AA, Dennison, EM, Cooper, C, Bafadhel, M, Barker, B, Brightling, C, Bolton, CE, John, ME, Parker, SG, Moffat, MF, Wardlaw, AJ, Connolly, MJ, Porteous, DJ, Smith, BH, Padmanabhan, S, Hocking, L, Stirrups, KE, Deloukas, P, Strachan, DP, Hall, IP, Tobin, MD, and Wain, LV

Abstract

BACKGROUND: Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants. OBJECTIVE: To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation. METHODS: 3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array. An analysis of risk of COPD was carried out using ever smoking controls (n=4784). Associations with %predicted FEV1 were tested in cases. We followed-up signals of interest (p<10(-5)) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays. RESULTS: Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10(-6), preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10(-6)). In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10(-6)). We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5. No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10(-7)). CONCLUSIONS: This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study.

Published
2016

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

Author

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

Published
2011

50. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author

STRAWBRIDGE RJ, DUPUIS J, PROKOPENKO I, BARKER A, AHLQVIST E, RYBIN D, PETRIE JR, TRAVERS ME, BOUATIA-NAJI N, DIMAS AS, NICA A, WHEELER E, CHEN H, VOIGHT BF, TANEERA J, KANONI S, PEDEN JF, TURRINI F, GUSTAFSSON S, ZABENA C, ALMGREN P, BARKER DJ, BARNES D, DENNISON EM, ERIKSSON JG, ERIKSSON P, EURY E, FOLKERSEN L, FOX CS, FRAYLING TM, GOEL A, GU HF, HORIKOSHI M, ISOMAA B, JACKSON AU, JAMESON KA, KAJANTIE E, KERR-CONTE J, KUULASMAA T, KUUSISTO J, LOOS RJ, LUAN J, MAKRILAKIS K, MANNING AK, MARTÍNEZ-LARRAD MT, NARISU N, NASTASE MANNILA M, OHRVIK J, OSMOND C, PASCOE L, PAYNE F, SAYER AA, SENNBLAD B, SILVEIRA A, STANCÁKOVÁ A, STIRRUPS K, SWIFT AJ, SYVÄNEN AC, TUOMI T, VAN 'T HOOFT FM, WALKER M, WEEDON MN, XIE W, ZETHELIUS B, DIAGRAM CONSORTIUM, GIANT CONSORTIUM, MANUNTA P, MUTHER CONSORTIUM, CARDIOGRAM CONSORTIUM, C4D CONSORTIUM, ONGEN H, MÄLARSTIG A, HOPEWELL JC, SALEHEEN D, CHAMBERS J, PARISH S, DANESH J, KOONER J, OSTENSON CG, LIND L, COOPER CC, SERRANO-RÍOS M, FERRANNINI E, FORSEN TJ, CLARKE R, FRANZOSI MG, SEEDORF U, WATKINS H, FROGUEL P, JOHNSON P, DELOUKAS P, COLLINS FS, LAAKSO M, DERMITZAKIS ET, BOEHNKE M, MCCARTHY MI, WAREHAM NJ, GROOP L, PATTOU F, GLOYN AL, DEDOUSSIS GV, LYSSENKO V, MEIGS JB, BARROSO I, WATANABE RM, INGELSSON E, LANGENBERG C, HAMSTEN A, FLOREZ JC, Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, BOUATIA-NAJI, N, Dimas, A, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, C, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, KERR-CONTE, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, MARTÍNEZ-LARRAD, Mt, Narisu, N, NASTASE MANNILA, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, VAN 'T HOOFT, Fm, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Manunta, P, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, SERRANO-RÍOS, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, F, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, and Florez, Jc

Published
2011

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