bioshareWe often get the question what the BioSHaRE-Eu consortium is. BioSHaRE is a consortium of leading biobanks and international researchers from all domains of biobanking science. The overall aim of the project is to build upon tools and methods available to achieve solutions for researchers to use pooled data from different cohort and biobank studies. This, in order to obtain the very large sample sizes needed to investigate current questions in multifactorial diseases, notably on gene-environment interactions. This aim will be achieved through the development of harmonization and standardization tools, implementation of these tools and demonstration of their applicability.

The mission of BioSHaRE is to ensure the development of harmonized measures and standardized computing infrastructures enabling the effective pooling of data and key measures of life-style, social circumstances and environment, as well as critical sub-components of the phenotypes associated with common complex diseases. For this we go beyond what individual biobanks can deliver.
Initially, BioSHaRE started with LifeLines, UK Biobank, HUNT, and KORA, and gradually we have been able to secure the collaboration of several other biobanks, like two Finnish cohorts (and access to data of many other Finnish cohorts), Prevend, two Bolzano cohorts, Estonia, NCDS, Pomerania, Cork&Kerry Diabetes & Heart studies, and some parts of EPIC. Eligible cohorts have >1000 participants and sufficient data to participate in the Healthy Obese project, BioSHaRE’s flagship research project.

(Healthy) Obesity
From its beginning, research with the tools delivered by BioSHaRE was an explicit goal, and one of the focuses is Healthy Obesity. As we have described on the BioSHaRE website, obesity is an important risk factor for type 2 diabetes mellitus and cardiovascular disease, and is associated with cancer, osteoarthritis and a reduced life expectancy. The clustering of metabolic and cardiovascular risk factors in obesity is known as the metabolic syndrome. However, not all obese individuals show an increased metabolic and cardiovascular risk, because a subset of obese subjects was found not to have impaired glucose tolerance, hypertension and dyslipidemia. They are known in literature as Metabolically Normal but Obese, Metabolically Healthy but Obese, or this phenomenon is referred to as isolated obesity or metabolically benign obesity. While the healthy obese population appears less vulnerable to develop DM and cardiovascular diseases, the risk towards developing cancer and osteoarthritis seems unaltered.

Characterization of the metabolically healthy obese is of importance for clinical practice and medical research. Studies suggest that weight loss in metabolically healthy obese individuals is not effective in further improving metabolic parameters or can even result in a paradoxical response. In medical research mixing of metabolically healthy and metabolically compromised subjects in one cohort of obese individuals could cause problems in statistical analysis and bias the outcome.
Current literature on the metabolically healthy obese is restricted to a few subpopulations and different criteria of metabolic health were used, ranging from the use of glucose metabolism alone to the assessment of a wide panel of biochemical parameters. There are only very limited studies in which the metabolically healthy obese phenotype is linked to prospective data.
Identification of the population with healthy obesity and subsequent analyses of (life style) determinants and consequences of the condition is of great importance to improve our understanding of obesity in general and to possibly identify preventive measures for the consequences of obesity.

The Healthy Obese Project (HOP) is the first scientific project to pool data of multiple biobanks to assess the following questions:
1. Evaluation of the prevalence of Healthy Obesity
2. Assessment of life style risk factors for Healthy Obesity
3. The clinical consequences of (Healthy) Obesity
4. Genetic modifications and advanced metabolic profiling related to questions 2 & 3

Current subprojects in HOP comprise:
Cross-sectional projects
1. Healthy Obesity and Diabetes
Lipid and blood pressure abnormalities across overweight & obese diabetics
Treatment of cardiovascular risk factors across Europe in diabetic subjects
The Healthy Obese type 2 diabetic: does he / she exist?
Genetics of a healthy c.v. risk profile in obesity and in subjects with type 2 diabetes
2. The influence of family history on Healthy Obesity
3. Health, obesity, and socioeconomic background
4. The influence of nutritional parameters on Health and Healthy Obesity
5. Interaction between smoking and alcohol consumption in Healthy Obesity
6. Healthy Obesity and physical activity
7. Healthy Obesity and inflammation
8. Is Healthy Obesity really Healthy Obesity: co-morbidities, medication use and quality of life in subjects with BMI>30 without metabolic syndrome
9. The ECG in Healthy Obesity: possible signs of silent ischaemia and other abnormalities
10. Weight bearing consequences of body weight in Healthy Obesity: athrosis, arthritis.
11. Prevalent diseases (cardiovascular, metabolic, weight bearing, reproduction, cancer, and physical fitness in general in (Healthy) Obese subjects
12. Cognitive functioning in (Healthy) Obesity
13. Socioeconomic factors, nutrition and food choices in (healthy) obesity
14. Is healthy obesity influenced by or associated with thyroid function ? Higher CRP and lower T3 in those who are unhealthy?

Prospective projects
1. Cardiovascular morbidity and Healthy Obesity: prospective c.v. events in moderately vs very obese subjects w. & w.o. the metabolic syndrome
2. Do Healthy Obese subjects develop disturbances in Quality of Life and Locomotion?
3. Development of pulmonary complaints in (Healthy) Obesity? Why do obese individuals have lower FEV1?
4. Weight bearing consequences of body weight in Healthy Obesity.
5. etc.

Such a cross-cohort evaluation of Healthy Obesity has never been performed. We intend to refine the concepts of metabolic syndrome, obesity and its sequelae by addressing the research questions and topics as mentioned above. Such activities are a perfect match for the recently announced HORIZON 2020 European program.

The current paper is the first of this unique collaboration, with the main focus on Healthy Obesity (=no metabolic syndrome components and no cardiovascular disease), and the first evaluation with so many cohorts involved, and as such is unique. I am not aware of similar papers addressing this topic for the individual cohorts (as the strength is the international harmonization between the cohorts and the pooling of large numbers of participants), but cohorts like HUNT and KORA have published about metabolic syndrome separately in the past, see examples.
Nevertheless, the aspect of healthy obesity has gained much attention the recent months, see for instance
BMC Public Health. 2014 Jan 8;14(1):14
Nutr Metab Cardiovasc Dis. 2013 Oct 9. pii: S0939-4753(13)00202-0. doi: 10.1016/j.numecd.2013.07.005
J Am Coll Cardiol. 2013 Dec 14. pii: S0735-1097(13)06480-2. doi: 10.1016/j.jacc.2013.10.080

I know of one HUNT paper in this area, http://www.sciencedirect.com/science/article/pii/S0735109713064814#
but BioSHaRE is not involved in this.

For LifeLines, we have published a paper on the effects of smoking on the individual components of the metabolic syndrome (BMC Medicine 2013 Sep 3;11:195. doi: 10.1186/1741-7015-11-195), and we are preparing a follow-up paper where we look into similarities and differences between the various cohorts as background nutrition and physical activity patterns will largely differ between – for instance – Finland, Italy and The Netherlands.

Examples:
Metabolic syndrome and risk of mortality in middle-aged versus elderly individuals: the Nord-Trøndelag Health Study (HUNT).
Hildrum B, Mykletun A, Dahl AA, Midthjell K.
Diabetologia. 2009 Apr;52(4):583-90. doi: 10.1007/s00125-009-1271-5. Epub 2009 Feb 5.

Age-specific prevalence of the metabolic syndrome defined by the International Diabetes Federation and the National Cholesterol Education Program: the Norwegian HUNT 2 study.
Hildrum B, Mykletun A, Hole T, Midthjell K, Dahl AA.
BMC Public Health. 2007 Aug 29;7:220.
I do hope that this gives some more insight in the BioSHaRE consortium, in which our department is participating, the project plans we have and the studies we are currently performing within the collaboration of these – currently 15 – cohorts.