Cohort Profile Update: The HUNT Study, Norway

Abstract

In the HUNT Study, all residents aged ≥20 years in the Nord-Trøndelag region, Norway, have been invited to repeated surveys since 1984-86. The study data may be linked to local and national health registries. The HUNT4 survey in 2017-19 included 56 042 participants in Nord-Trøndelag and 107 711 participants in the neighbouring Sør-Trøndelag region. The HUNT4 data enable more long-term follow-up, studies of life course health trajectories and within-family studies. New measures include body composition analysis using bioelectrical impedance; a 1-week accelerometer recording; physical and cognitive testing in older adults; measurements of haemoglobin and blood cell counts, HbA1c and phosphatidylethanol; and genotyping. Researchers can apply for HUNT data access from HUNT Research Centre if they have obtained project approval from the Regional Committee for Medical and Health Research Ethics, see [www.ntnu.edu/hunt/data]. The Trøndelag Health Study (the HUNT Study) is a population-based cohort study of the adult population in Trøndelag County, Norway. It was previously called the Nord-Trøndelag Health Study, until the study in 2019 expanded to cover both regions of Trøndelag County, Nord-Trøndelag and Sør-Trøndelag. The study has been running in Nord-Trøndelag since 1984 and is designed to cover a broad range of health-related topics through repeated surveys with questionnaires, interviews, clinical examinations, laboratory measurements and storage of biological samples. Nord-Trøndelag is fairly representative of Norway except for the lack of large cities and immigrant populations, and the region is suitable for longitudinal studies due to low migration. The HUNT Study data can be linked to a wide range of local and national health registries by means of the unique identification number allocated to all Norwegian residents. All current residents ≥20 years of age in Nord-Trøndelag have been invited to each survey wave: the HUNT1 (1984–86, 77 202 participants, 89.4% of invitees participated),1 HUNT2 (1995-97, 65 228 participants, 69.5%)2 and HUNT3 (2006-08, 50 800 participants, 54.1%)3 surveys (Figure 1). Since 1995-97, all adolescents (13-19 years of age) in Nord-Trøndelag have been invited to participate in the corresponding Young-HUNT Study.4 Flowchart of participation across the HUNT1–HUNT4 surveys and details on recruitment to HUNT4. The few individuals who have withdrawn their consent to participate in the HUNT Study have been excluded, and the numbers therefore deviate slightly from those reported in previous HUNT cohort profiles. NT, Nord-Trøndelag region; ST, Sør-Trøndelag region In 2017–19, all adult residents of Trøndelag were invited to the HUNT4 survey. The reasons for this new survey were, first, to collect follow-up and extended information on previous participants, and new information on individuals having moved into the region or reached adult age. After completion of HUNT4, about 19 000 individuals have more than 30 years of follow-up spanning all four study cycles (Figure 1). The continued follow-up also allows for monitoring of secular trends in public health. Second, improved measurement methods have become available for several health and lifestyle characteristics important for public health, as described in the later sections. Third, the HUNT Study previously lacked data from a large city. In 2019, HUNT4 expanded to include a survey in Sør-Trøndelag, which includes the city of Trondheim with ∼202 000 inhabitants (2019). The extended study population from both Nord-Trøndelag and Sør-Trøndelag is generally representative of Norway (Supplementary Table S1, available as Supplementary data at IJE online). A fourth reason for new data collection is the expansion of genetic and molecular epidemiology, where 70 517 participants of the HUNT2 or HUNT3 surveys have been genotyped. Extended follow-up of HUNT participants and high attendance among older adults enable a stronger focus on disease incidence, progression and life course health trajectories. New generations of HUNT participants enable more within-family and intergenerational studies. More valid studies of physical activity and anthropometry are possible due to new data including accelerometer recordings and body composition analyses using bioelectrical impedance. Other new assessments include cognitive and physical testing in old age, fecal sampling for microbiome studies and metabolomics and proteomics analyses for deeper molecular phenotyping. With available genotype information, analyses are expanded to, for example, genome-wide association studies and Mendelian randomization. In Nord-Trøndelag, all residents aged ≥20 years at the estimated time of survey participation were invited to HUNT4 between 29 August 2017 and 23 February 2019 (the HUNT4-N Survey). Out of 103 800 invitees, 56 042 (54.0%) participated, defined as returning the main questionnaire. Participation across the HUNT1-HUNT4 surveys is shown in Figure 1. In Sør-Trøndelag, all residents aged ≥18 years were invited to the HUNT4-S Survey and 107 711 (42.6%) participated out of 252 991 invitees. HUNT4-S consisted of two parts: 1745 residents ≥70 years of age in districts of Trondheim municipality took part in an examination between 26 October 2018 and 12 June 2019, and the remainder took part in a questionnaire survey between 3 October 2019 and 19 November 2019. With the completion of HUNT4-N, 123 004 residents in Nord-Trøndelag have participated in at least one HUNT survey, of whom 68 586 have participated in more than one survey and 5881 participated in the Young-HUNT Study as adolescents. With the completion of HUNT4-S, 230 617 individuals have participated in one or more of the HUNT surveys. Characteristics of HUNT4 participants are given in Table 1. Participation in HUNT4 differed by age, being highest in the age groups 40-79 years, and also slightly differed by marital status and urban vs rural residency (Table 2). Attrition from HUNT3 to HUNT4 was highest in older adults and was also moderately higher among people with chronic diseases or poor self-rated health or who were smokers (Supplementary Table S2, available as Supplementary data at IJE online). Questionnaire surveys were performed among non-participants of HUNT4-N and previous HUNT participants who were not invited to HUNT4-N because they had emigrated from the study area (Table 3;Supplementary Table S3, available as Supplementary data at IJE online). Those who had emigrated reported lower body mass index (BMI), more physical activity, less smoking, better self-rated health and more frequent alcohol intake than both participants and non-participants. The non-participants had less healthy lifestyle, lower self-reported health and higher proportion of cardiovascular diseases, chronic obstructive pulmonary disease, diabetes and antihypertensive medication use. Characteristics of participants in the HUNT4 Survey (HUNT4-N and HUNT4-S), reported as percentagesa unless otherwise noted COPD, chronic obstructive pulmonary disease; IQR, interquartile range; SD, standard deviation; NA, not available. Calculated among people with valid information, which ranges from 89% to 100% for individual items. The survey was conducted in Nord-Trøndelag between 29 August 2017 and 23 February 2019 (the survey includes a pilot study performed in May 2017). Characteristics are presented for the 56 042 individuals who participated in HUNT4-N by returning the main questionnaire. In addition, 897 individuals took part in the clinical examination, but did not return the questionnaire; these individuals were more often older adults included in the HUNT70+ study part that will be described in a separate paper. The survey was conducted in Sør-Trøndelag as a questionnaire survey between 3 October and 19 November 2019 (105 966 participants) or as an examination among residents ≥70 years in districts of Trondheim municipality between 26 October 2018 and 12 June 2019 (1745 participants). The 252 991 invitees to HUNT4-S include all adult residents of Sør-Trøndelag, except former Nord-Trøndelag residents who had moved to Sør-Trøndelag after previously participating in HUNT and were instead invited to an emigrant survey. All residents aged ≥20 years at the estimated time of survey participation were invited, and some were aged 19 years at the date of participation. Years of education based on self-reported level of education: primary school ≤10 years; academic or vocational school/apprentice 11–13 years; and university college or university ≥14 years. Units (12.8 g alcohol) calculated based on the self-reported usual number of glasses of beer/wine/liquor per 2 weeks or, if that information was missing, estimated from the reported frequency of alcohol consumption during the past year. For participants of the questionnaire survey in HUNT4-S, this was calculated from self-reported weight and height. Mean of the second and third measurements. For 0.4% of participants who had only two valid blood pressure measurements, we used the second measurement. Estimated using the equation developed by Sampson M et al., JAMA Cardiol 2020;5:540–48. Estimated using the Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) equation. Characteristics of participants in the HUNT4 Survey (HUNT4-N and HUNT4-S), reported as percentagesa unless otherwise noted COPD, chronic obstructive pulmonary disease; IQR, interquartile range; SD, standard deviation; NA, not available. Calculated among people with valid information, which ranges from 89% to 100% for individual items. The survey was conducted in Nord-Trøndelag between 29 August 2017 and 23 February 2019 (the survey includes a pilot study performed in May 2017). Characteristics are presented for the 56 042 individuals who participated in HUNT4-N by returning the main questionnaire. In addition, 897 individuals took part in the clinical examination, but did not return the questionnaire; these individuals were more often older adults included in the HUNT70+ study part that will be described in a separate paper. The survey was conducted in Sør-Trøndelag as a questionnaire survey between 3 October and 19 November 2019 (105 966 participants) or as an examination among residents ≥70 years in districts of Trondheim municipality between 26 October 2018 and 12 June 2019 (1745 participants). The 252 991 invitees to HUNT4-S include all adult residents of Sør-Trøndelag, except former Nord-Trøndelag residents who had moved to Sør-Trøndelag after previously participating in HUNT and were instead invited to an emigrant survey. All residents aged ≥20 years at the estimated time of survey participation were invited, and some were aged 19 years at the date of participation. Years of education based on self-reported level of education: primary school ≤10 years; academic or vocational school/apprentice 11–13 years; and university college or university ≥14 years. Units (12.8 g alcohol) calculated based on the self-reported usual number of glasses of beer/wine/liquor per 2 weeks or, if that information was missing, estimated from the reported frequency of alcohol consumption during the past year. For participants of the questionnaire survey in HUNT4-S, this was calculated from self-reported weight and height. Mean of the second and third measurements. For 0.4% of participants who had only two valid blood pressure measurements, we used the second measurement. Estimated using the equation developed by Sampson M et al., JAMA Cardiol 2020;5:540–48. Estimated using the Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) equation. Relative probability of participation in HUNT4-N and HUNT4-S by sociodemographic characteristics Percentage among the total number of invitees in the category. Age-adjusted relative probability of participation. Relative probability of participation in HUNT4-N and HUNT4-S by sociodemographic characteristics Percentage among the total number of invitees in the category. Age-adjusted relative probability of participation. Content of the HUNT4-N and HUNT4-S surveys BW, bitewing; CAM, complementary and alternative medicine; CRP, C-reactive protein; FFQ, Food Frequency Questionnaire; HDL, high-density lipoprotein; MRI, magnetic resonance imaging; OPG, orthopantomogram; PEth, phosphatidylethanol; Q, questionnaire; TPO, thyroid peroxidase, TSH, thyroid stimulating hormone. No overlap with random samples for the lung study, the osteoporosis study or the arthritis study. Overlap with the Oral Health Study. The number 51 477 refers to the body composition analysis, which had fewer participants as not all participants could be measured barefoot. No overlap with random sample for the lung study, the osteoporosis study or the arthritis study. Examinations only in larger municipalities (Stjørdal, Levanger, Verdal, Steinkjer, Namsos and Nærøy), but questionnaires in all municipalities. Content of the HUNT4-N and HUNT4-S surveys BW, bitewing; CAM, complementary and alternative medicine; CRP, C-reactive protein; FFQ, Food Frequency Questionnaire; HDL, high-density lipoprotein; MRI, magnetic resonance imaging; OPG, orthopantomogram; PEth, phosphatidylethanol; Q, questionnaire; TPO, thyroid peroxidase, TSH, thyroid stimulating hormone. No overlap with random samples for the lung study, the osteoporosis study or the arthritis study. Overlap with the Oral Health Study. The number 51 477 refers to the body composition analysis, which had fewer participants as not all participants could be measured barefoot. No overlap with random sample for the lung study, the osteoporosis study or the arthritis study. Examinations only in larger municipalities (Stjørdal, Levanger, Verdal, Steinkjer, Namsos and Nærøy), but questionnaires in all municipalities. Similar to previous HUNT surveys, HUNT4-N consisted of questionnaires, a short interview, clinical examination and biological sampling, and was conducted by trained health professionals at examination stations in each of 23 municipalities in Nord-Trøndelag. HUNT4-S was mainly a web-based questionnaire survey (except for the examination of 1745 residents ≥70 years of age in Trondheim), but printed questionnaires were sent on request and to older adults. The HUNT4 questionnaires covered a broad range of topics including socioeconomic conditions, health-related behaviours, symptoms, conditions and diseases, as described in Table 3. Selected HUNT4-N participants were also asked to complete questionnaires related to specific health topics, and a 19% random sample aged 20-69 years was invited to complete a web-based food frequency questionnaire.5 To evaluate the quality of the self-report of conditions in HUNT4, we compared the self-reported information with diagnostic codes recorded in the local or regional hospitals and on general practitioners’ reimbursement forms. Compared with these diagnoses as a reference standard, the sensitivity, specificity and predictive values of the self-reported information varied across diagnoses in both HUNT4-N (Supplementary Table S4, available as Supplementary data at IJE online) and HUNT4-S (Supplementary Table S5, available as Supplementary data at IJE online). Of note, the diagnostic codes may be inaccurate and do not constitute a definite reference standard. For example, in absence of a more suitable diagnostic code, a disease diagnosis may likely be reported on the reimbursement form by a general practitioner if a patient comes for testing for that disease, even if the disease was not confirmed. In-depth validity studies have been conducted for self-reported headache6 and insomnia7 in HUNT4. Validity studies of self-report of, for example, diabetes,8 psoriasis9 and atrial fibrillation,10 have been performed after previous HUNT surveys. An overview of HUNT4 measurements, performed as part of the main HUNT4 examination or as ancillary data collections, is provided in Table 3. New aspects of the clinical examination in HUNT4-N compared with previous HUNT surveys included detailed body composition analysis using bioelectrical impedance (InBody 770, Cerritos, CA, USA), a 1-week accelerometer recording (AX3, Axivity, Newcastle, UK) and physical and cognitive testing [Short Physical Performance Battery (SPPB), grip strength and Montreal Cognitive Assessment, (MoCA); participants ≥70 years of age]. Blood pressure, pulse and peripheral capillary oxygen saturation were recorded three times at 1-min intervals using Dinamap CARESCAPE V100 (GE Healthcare, Chicago, IL, USA). Oral health clinical and radiographic examinations [Planmeca ProOne (orthopantomogram) and Planmeca Intra/Prostyle Intra with ProSensor HD (bitewing), Helsinki, Finland], hearing test (air-conduction pure-tone audiometry at 0.25-8 kHz according to ISO 8253-1 using Interacoustics audiometers type AD629 with TDH-39P supra-aural audiometric earphones) and spirometry (Jaeger Masterscope spirometers, JLAB version latest upgrade 2016, CareFusion, Würzburg, Germany) were performed in selected samples, and other tests have subsequently been performed in subgroups. All participants provided blood samples drawn in a non-fasting state between 9 am and 8 pm and time since last meal was recorded. Biological sampling at the field stations included blood, urine and saliva, and feces kits were returned in pre-paid envelopes. Biological material was handled at the field stations according to appropriate standards and transported to the biobank every evening in a cold chain. For all participants, two blood tubes were delivered at the laboratory of Levanger Hospital, Nord-Trøndelag Hospital Trust the next day for immediate analyses or transport to other laboratories. New analyses in blood included haemoglobin (Hb) and blood cell counts, HbA1c and phosphatidylethanol (PEth, an indicator of alcohol intake). Three blood tubes were aliquoted and stored in automated freezers in HUNT Biobank. Since the publication of the original cohort profile in 2013,3 new analyses of biological material stored in HUNT Biobank include the genotyping of 70 517 participants of HUNT2 or HUNT3, genotyping of 18 098 additional participants of HUNT4-N,11 and SomaLogic’s SomaScan proteomics analyses12 and measurements of vitamin D13 and troponin I14 in subsamples. The HUNT participants have consented to linkage to the many high-quality health and administrative registries in Norway, and to information from medical records. Such linkages can be reliably made using the national identification numbers allocated to all Norwegian residents, and means that prospectively recorded information on health outcomes can be obtained also for participants who do not attend subsequent HUNT surveys. An overview of Norwegian health registries is given by the Directorate for e-Health at Helsedata.no In Table we characteristics of the HUNT4-N and HUNT4-S participants, including of a range of chronic conditions and The longitudinal of HUNT analyses of long-term population in health-related For example, of HUNT4-N with previous HUNT surveys the of smoking, high blood pressure and has from the until the of and diabetes has (Figure Table available as Supplementary data at IJE online). the of diabetes has HbA1c measurements in HUNT4 that the current of diabetes is The of has and medication have become less as has hearing from HUNT4 has of cognitive and and and of the longitudinal in of HUNT4 have shown that is with higher of C-reactive and chronic and that cognitive is with lower physical of cardiovascular in HUNT1 HUNT2 HUNT3 and HUNT4-N by using age to the Norwegian population years and older on with intervals are provided in Supplementary Table as Supplementary data at IJE online) The new focus on genetic and molecular has for example, genome-wide association studies new genetic with atrial thyroid stimulating and Mendelian studies have the between and and provided for the of on of higher body mass on and and of on and measures spanning have body mass index more in individuals during to a more The predictive of in cardiovascular has been using proteomics The large number of participating in HUNT has within-family studies. analyses have that as by that is to be a of outcomes in population-based samples of Mendelian analyses have for for example, studies of the of and body mass on Table as Supplementary data at IJE online) of studies HUNT data have been used across a range of health topics since the original cohort profile was in HUNT is suitable for longitudinal studies due to the long-term follow-up with repeated measurements since the low for and available valid information on and from the The HUNT surveys cover a broad range of health-related topics, and many questionnaire have been across the surveys to enable longitudinal HUNT data are stored at the HUNT and biological material is stored in the HUNT Biobank at the HUNT Research the HUNT Study has invited the population in the area the study population includes many both and across and is therefore suitable for within-family studies. A compared with many other studies is available information in adult The study population has that may have to be in the of, for example, but is with a of using The high participation a generally lower for from HUNT3 to HUNT4 was higher among participants with chronic diseases or other of health, and lifestyle differed among non-participants and compared with participants of HUNT4. To about participation by health among all HUNT4 invitees, we also primary health diagnostic codes across a range of diseases, as as primary health for HUNT4 invitees and participants recorded during the 2017 or 2019 The proportion being each diagnostic generally did not between participants and invitees, but between diagnoses as detailed in Supplementary Table as Supplementary data at IJE online). For example, a diagnosis was less often recorded among participants than among invitees. were more frequent among participants than non-participants at years. In and residency were more among non-participants (Supplementary Figure S1, available as Supplementary data at IJE online). The population the to people of Researchers to a Norwegian can apply for HUNT data access from HUNT Research Centre if they have obtained project approval from the Regional Committee for Medical and Health Research Researchers not to a Norwegian with and apply through a Norwegian on the and conditions for data access is available at [www.ntnu.edu/hunt/data]. The HUNT a detailed overview of the available in HUNT data from ancillary HUNT may be to a provided to the who have and conducted the data Biological material is available for and information on is at the HUNT Biobank from the health registries are not by linkages between HUNT and data have to be made for each project and that the has obtained approval for linkage by and each The presented in this was by the Regional Committee for Medical and Health Research of the Supplementary data are available at IJE and participated in or data of the HUNT4 and the and the data with from and and the and all the The Trøndelag Health Study is a collaboration between HUNT Research Centre of and Health Norwegian of and Trøndelag Norway Regional Health and the Norwegian of the population of Trøndelag for their to with important data and biological and and in all municipalities for and of the administrative at HUNT Research Centre for to the collection and storage of data and biological For this Nord-Trøndelag Hospital Trust provided diagnostic codes from Nord-Trøndelag Hospital Trust and Hospital, and the Norwegian Directorate of Health provided data from the and the Norwegian for Health The and of these data are the of the and by the Norwegian for Health is be

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