LifeLines Cohort Study & Biobank (LifeLines)

Overall aim of the LifeLines study is to unravel the interaction between genetic and environmental factors in the development of multifactorial diseases, their concurrent development in individuals and their complications as a complex trait. The primary objectives are to establish which are the disease overriding risk factors which predict the development of a multifactorial disease during lifetime, and how are these universal risk factors modified, or what determines the effect of a universal risk factor in an individual. Specific research questions will focus on risk factors and modifiers (genetic, environmental and combined or complex factors) for single and multiple diseases. In addition to co-morbidity, LifeLines focuses on co-determinants. The primary endpoints include measures of ageing, metabolic and endocrine diseases, cardiology, renal diseases, pulmonary and musculoskeletal diseases, and psychopathology. Secondary objectives: Secondary aims include the assessment of the prevalence and incidence of multifactorial diseases and their risk factors in individuals as well as in families. The burden of disease for the society will be quantified in terms of care needed, and total costs of care.

General Information

General Design

Study design: 
Cohort study
General Information on Follow Up (profile and frequency): 

At baseline, all participants received a number of questionnaires and a basic medical examination at a local LifeLines research facility. Urine and blood samples were collected for storage and for laboratory measurements. The participants are followed for at least 30 years and are invited every 5 years for a visit to the LifeLines research facility. In the years in between the participants receive follow-up questionnaires. Follow-up on morbidity and mortality are also based on general practitioners, hospital and pharmacy records. Additional examinations or questionnaires in subgroups of participants to investigate specific research questions are possible.

Recruitment target: 
Families (including twin studies, sibships and family based birth cohorts)
Target number of participants: 
165 000
Target number of participants with biological samples: 
165 000
Supplementary information about target number of participants: 

All LifeLines participants have been included. The cohort consists of more than 165.000 individuals. The aim was to include 45 000 probands, 30000 partners, 55000 parents (including in laws) and 35000 children. LifeLines is at the moment working out all probands. 

Supplementary information: 

A selection of general practitioners from the three northern provinces of the Netherlands, Groningen, Friesland and Drenthe invited all their listed patients between 25 and 50 years of age. These probands were asked to invite their parents, partner(s), parents in law and children to participate as well. Besides this, also other persons who were interested to participate were able to register.

In LifeLines participants of all ages were included. Based on the age of the participant, he or she was included in the children’s cohort (0-18 years), the adult cohort (18-65 years) or the elderly cohort  (>65 years). The major part of the protocol and therefore the measurements are the same for all participants. However, parts of the protocol are adjusted for each cohort to suit with the characteristics of the specific age group. For children five specific sub- protocols were developed, corresponding with the different developmental stages. 

All participants received written information on the purpose and methods of the study. Before signing the Informed Consent form partipants had the opportunity to discuss the study with the LifeLines staff. All data are kept strictly confidential and are only used for medical research by qualified scientists. LifeLines reports unexpected abnormal values to both the participant and his or her general practitioner.


Access to external researchers or third parties provided or foreseen for
Data (questionnaire-derived, measured...): 
Biological samples: 
Yes -

GIS (geographic information system) data

Marker Paper

Marker paper: 
Stolk RP, Rosmalen JG, Postma DS, de Boer RA, Navis G, Slaets JP, Ormel J, Wolffenbuttel BHR. Universal risk factors for multifactorial diseases: LifeLines: a three-generation population-based study. Eur J Epidemiol 2008; 23(1): 67-74.
Pubmed ID: 

Supplementary Information

Endpoint data not available [Feb 2015]. Disease groups of interest are:

  • Neoplasms (C00-D48)
  • Endocrine, nutritional and metabolic diseases (E00-E90)
  • Mental and behavioural disorders (F00-F99)
  • Diseases of the circulatory system (I00-I99)
  • Diseases of the respiratory system (J00-J99)
  • Diseases of the digestive system (K00-K93)
  • Diseases of the skin and subcutaneous tissue (L00-L99)
  • Diseases of the musculoskeletal system and connective tissue (M00-M99)
  • Diseases of the genitourinary system (N00-N99)

The LifeLines Cohort Study is supported by the Netherlands Organization of Scientific Research NWO (grant 175.010.2007.006), the Economic Structure Enhancing Fund (FES) of the Dutch government, the Ministry of Economic Affairs, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the Northern Netherlands Collaboration of Provinces (SNN), the Province of Groningen, the city of Groningen, the University Medical Center Groningen, the University of Groningen, Dutch Kidney Foundation and Dutch Diabetes Research Foundation. Funding for Global Harmonisation and standardisation of datacollection and for participation in Biobank Research projects is provided by the European Committee via Framework Programme 7.


Study Timeline

Each colour in the timeline graph below represents a separate Study Population, while each segment in the graph represents a separate Data Collection Event. Clicking on a segment gives more detailed information on a Data Collection Event.
  • LifeLines population


LifeLines population

The study population consists of a representative sample of the population of the northern provinces of the Netherlands, covering three generations. The LifeLines project includes more than 165.000 participants. It was aimed for to include approximately 45.000 probands, 30.000 partners, 55.000 parents-(in law) and 35.000 children. LifeLines is currently working out all family ties. Based on the age of the participant, he or she is included in the children’s cohort (0-18 years), the adult cohort (18-65 years) or the elderly cohort (>65 years).

Selection criteria: 

Three Northern provinces: Groningen, Friesland and Drenthe

Health status:
Severe psychiatric or physical illness are excluded
Sources of recruitment: 
General population:
Volunteer enrolment
Number of participants: 
165 000 participants
Number of participants with biological samples: 
165 000 participants
Supplementary information about number of participants: 

More than 165000 participants are included in the LifeLines cohort

Data Collection Events:
Preparation phase/pilot2004 (January)2006 (December)
Baseline visit

Baseline visit of participants.

2007 (January)2013 (December)
Follow-up questionnaire 1

Follow-up of participant at 1.5 years after Baseline visit. 

2010 (January)2014 (December)
Follow-up questionnaire 2

Follow-up of participants at 3 years after Baseline visit.

2012 (January)2015 (December)
Follow-up questionnaire 3

Follow-up of participants at 5 years after Baseline visit.

2014 (January)2017 (December)
Follow-up visit 1

Follow-up visit of participants at approx. 5 years after Baseline visit.

2014 (January)2017 (December)



Lifelines - Baseline Exposure information...