Cohort Profile: WELL Living Laboratory in China (WELL-China)

Abstract

Key Features WELL-China is a prospective longitudinal study for the investigation of well-being. The cohort aims to assess multidimensional well-being in a large sample and provides a platform for future intervention studies to help promote well-being at individual and community levels. A total of 10 268 participants aged between 18 and 80 years were recruited from the City of Hangzhou, China between 2016 and 2019; ∼40% of the cohort are men. Follow-up will take place between 2020 and 2021, and will reoccur every 2 years; the nested-omics sub-cohort will be followed every 6 months. WELL-China has collected in-person survey data, physical and clinical examinations, laboratory tests and biospecimens. The survey included >1000 questions and includes the Stanford WELL for Life Scale, lifestyle behaviours, eye disease and traditional Chinese medicine body constitutions. In-person examinations included anthropometrics, functionalities, vitals, eye exams, traditional Chinese medicine diagnosis and abdominal ultrasound. Laboratory tests included complete blood count, liver and renal panel, lipid panel, etc. Biospecimens included blood, stool, hair and toenails, which were collected at baseline. Specimens have been processed and aliquoted for storage at –80°C in a freezer. Currently, WELL-China has >200 000 aliquots of biospecimens in the WELL-China biobank. A subset of 250 participants also currently have microbiome and metabolomic information. WELL-China data contain several unique features. The novel Stanford WELL for Life Scale quantifies one’s overall well-being and domain-specific well-being. Dual-energy X-ray absorptiometry (DXA) scans provide detailed information on body composition and bone mineral density. Thorough eye examinations and ophthalmology surveys are unique compared with other China-based cohorts. Abdominal ultrasound provides important information to identify fatty liver diseases, including non-alcoholic fatty liver disease. The cohort setup also permits the rapid implementation of intervention testing. WELL-China welcomes collaborations globally. Applicants must submit an ancillary study application package including a research proposal, requested variables and biospecimens. For more information, please contact [email protected] (the USA-based PI) or [email protected] (the China-based PI). China’s rapid economic growth over the past 40 years, with an average annual gross domestic product growth of 6.6% through 2018, has moved nearly 800 million people out of poverty1–3 and generated substantial gains in living standards, healthcare systems and health outcomes.4,5 The accompanying changes in dietary habits, lifestyles and built environment shift healthcare challenges from infectious diseases to non-communicable diseases.6,7 At the same time, the improved living conditions heighten the concept and awareness of ‘living well’ and ‘holistic health’ at both individual and population levels. Instead of focusing on the absence of disease, individuals and communities have started to pursue positive physical and mental functionalities.8 The promotion of ‘well-being’ for the purpose of living a more fulfilling and meaningful life has gained remarkable momentum.9,10 Researchers, over the last several decades, have attempted to define and quantify ‘well-being’.10,11 Spiritual, psychological (positive affect, life satisfaction) and social aspects of well-being have been used as the outcomes in medical, psychological, sociological and economic studies.12–15 However, the meaning of well-being differs by disciplines and individuals, and has not been comprehensively measured longitudinally in large-scale cohort settings. The WELL Living Laboratory-China (WELL-China) study, an ongoing prospective cohort, is a joint endeavour led by Stanford University in the USA and Zhejiang University in China. The main objective of this cohort is to assess and define well-being in the cultural context and comprehensively measure individual-level well-being in a longitudinal setting. In addition to China, there are three parallel WELL study sites: the San Francisco Bay Area, New Taipei City and Singapore. Together, they constitute the Stanford WELL for Life Studies. The sites use a common protocol but with different subject-recruitment strategies based on the circumstances in each site. One of the goals of this global collaboration and research is to allow comparisons of health and well-being between sites and across racial-ethnic backgrounds. WELL-China is located in the City of Hangzhou, Zhejiang Province. With well-being as the primary outcome, this study aims to investigate the determinants, patterns and consequences of well-being and to improve well-being at both individual and community levels through effective interventions. To assess well-being, the Stanford Prevention Research Center has developed a novel well-being questionnaire to encompass the multidimensional nature of well-being globally. WELL-China has enrolled 10 268 individuals with comprehensive data collection, including an extensive in-person survey that incorporates the Stanford well-being questionnaire, physical and clinical examinations, laboratory tests and biospecimen storages. The WELL-China cohort recruited participants from three districts in the City of Hangzhou from November 2016 to May 2019. Hangzhou was chosen for the its similar size, climate and diversity of population in Hangzhou (7.9 million) compared with the San Francisco Bay Area (7.5 million).16 Despite its large population, Hangzhou is not considered a mega-city in China and its experience in population growth, rapid urbanization and economic expansion is considered to be representative of the many large Chinese urban centres undergoing similar changes the last 20 years. Similar to the San Francisco Bay Area (having nine counties), Hangzhou also has nine administrative districts, with a total population size in these nine districts ranging from 350 000 to 1.7 million.17–19 We selected three out of the nine districts, namely Xihu, Shangcheng and Gongshu, based on the demographic characteristics, as well as the commitment and support from the district governments. Figure 1 summarizes the study timelines and cohort information. WELL-China framework for a target of 10 000 participants Within each district, there are two administrative levels: subdistrict and community. For each of the three districts, we sampled from all of the subdistricts and all the communities within each subdistrict. We applied quota sampling to identify individuals within each community. Stratifications for quota sampling were based on sex (male and female with equal quota) and age groups (18–39, 40–59, 60–80 years, proportional to the population age distribution). The sampling frame used to identify individuals was the household registration at each community, which included all the long-term residents. Long-term residents were defined as individuals who have resided in Hangzhou for >6 months. Target sample sizes for the three districts were 3000, 3000 and 4000, respectively. Within each district, the sample size for each subdistrict was the district target sample size divided by the number of subdistricts. Eligible participants were between 18 and 80 years old, and were long-term residents of the selected district (including residents who had their residential registration in Hangzhou; who had resided in the district for >6 months and planned to stay within the same city for at least the upcoming 2 years, and had a registered residential address). Exclusion criteria were serious medical conditions, mental impairment and pregnancy or planned pregnancy during the data-collection phase. Recruitment was carried out in three steps (Figure 2): initial contact/invitation, confirmation of participation and community registration. Social workers identified potentially eligible participants by comparing individuals in the community household registration database against the inclusion and exclusion criteria. Social workers then contacted the eligible individuals by either phone or door-to-door visits to introduce the WELL-China study using standardized IRB-approved materials. They kept a list of individuals who showed an interest in the study. Within 2 weeks, research fieldworkers contacted interested individuals via phone and confirmed the date, time and location of in-person registration at the local community centre. At the in-person registration, research fieldworkers verified eligibility and participants completed an in-person registration form, signed the informed consent, picked up stool-collection kits with detailed instructions and scheduled an appointment for an in-person lab visit to Zhejiang University within 2 days. Round-trip transportation to and from the lab was provided for the participants. WELL-China recruitment strategy At the closure of the baseline in May 2019, we had enrolled a total of 10 268 participants into the WELL-China study. As shown in Figure 1, 3070, 3064 and 4144 participants were recruited from each of the three districts with a response rate of 75%, 90% and 90%. The response rate is calculated as the proportion of participants completing the in-person survey among those completing the community-based registration. Of the 10 268 participants, 99.7%, 83.0%, 91.2% and 91.8% provided blood, stool, hair and nail samples, respectively. Basic demographics of these participants are shown in Table 1. Approximately 40% of the participants were male and the mean age was 55 years for men and 54 years for women. Most participants (79%) had a middle-school education level. The vast majority were married (men 89%, women 86%) and almost all (95%) had health insurance. WELL-China baseline characteristics, by sex NAs refers to participants missing the corresponding variable. Income has been converted into US dollars. Well-being score was calculated using the Stanford WELL for Life Scale. SD refers to the standard deviation of the well-being score. Such as yogurt and other food or supplements rich in live microorganisms. Such as dietary fibre and other chemicals that nourish the gut microorganism. WELL-China baseline characteristics, by sex NAs refers to participants missing the corresponding variable. Income has been converted into US dollars. Well-being score was calculated using the Stanford WELL for Life Scale. SD refers to the standard deviation of the well-being score. Such as yogurt and other food or supplements rich in live microorganisms. Such as dietary fibre and other chemicals that nourish the gut microorganism. Two levels of follow-up will be carried out starting in late autumn 2020: the biennial active follow-up of the entire cohort and the biannual follow-up of a nested-omics cohort of 250–500 participants. The WELL-China team will, again, closely collaborate with community social workers and other relevant personnel to motivate the follow-up participation among the original participants. Figure 3 delineates the follow-up timeline and data to be collected at each scheduled time point. At each follow-up, all participants will be invited to repeat the baseline procedures and assessments (in-person survey, physical and clinical examinations, laboratory tests, biospecimen collection). Individuals in the nested-omics cohort will be followed up biannually to generate repeated measures of well-being and gut microbial and metabolomic profiles. In the follow-ups, we are planning to incorporate built-environment information, including neighbourhood environmental scans and individual-level environmental exposures. The former will capture built, food and natural environments using a digital environmental audit tool, whereas the latter will profile the individual exposome and technology environment. Environmental data will be updated biennially. In addition, we will determine loss-to-follow-up rates and response rates to guide future studies. WELL-China follow-up timeline At baseline, we collected the following information from the entire cohort: in-person survey, physical and clinical examinations, laboratory tests and biospecimens. We also obtained gut-microbiome and metabolomics information from a nested cohort of 250 individuals. The last column of Table 1 presents the basic demographic information for the nested cohort. Table 2 summarizes the components of the data collection at baseline, including all the survey modules and the number of questions in each module, physical- and clinical-examination items, and the number of repeated measurements taken for each item, all variables included in the laboratory tests and biospecimens gathered at baseline and their corresponding quantities. A list of equipment used in the baseline data collection is included in Supplementary Table 1, available as Supplementary data at IJE online. WELL-China baseline data components Basic information (demographics, socio-economics) (69) Stanford WELL for Life Scale (SWLS) (76) Quality of life (EQ-5D-5L,a WHO-5,b Ruler Scale) (12) Lifestyle behaviours Smoking (20) Alcohol drinking (8) Coffee, tea, water (9) Physical activity (IPAQc) (15) Self-reported anthropometrics and body image (13) Pittsburg Sleep Quality Index (12) Eating habit (34) 26-item food frequency (52) Gastroenterological symptoms (15) Traditional Chinese medicine (TCM) body constitution (54) Eye disease (ODSI,d LVQOLe) (37) Sleep apnoea (STOP-Bang,f Cohort 3 only) (5) Medical histories History of disease and medication use (432) Menstrual history (43) Family nistory (28) Healthcare-service utilization (including TCM) (62) Biospecimen for storage Blood samples (whole blood, serum, plasma, white blood cells) (15 ml) Stool samples (20 ml) Hair samples (>0.25 g) Toenails (>0.5 g) Nested-omics cohort (N = 250) Microbiome Metabolomics Anthropometrics (number of measurements) Standing height height bone mineral (DXA) bone mineral (DXA) Blood rate Eye Traditional Chinese medicine diagnosis Abdominal ultrasound 3 only) blood Blood Basic information (demographics, socio-economics) (69) Stanford WELL for Life Scale (SWLS) (76) Quality of life (EQ-5D-5L,a WHO-5,b Ruler Scale) (12) Lifestyle behaviours Smoking (20) Alcohol drinking (8) Coffee, tea, water (9) Physical activity (IPAQc) (15) Self-reported anthropometrics and body image (13) Pittsburg Sleep Quality Index (12) Eating habit (34) 26-item food frequency (52) Gastroenterological symptoms (15) Traditional Chinese medicine (TCM) body constitution (54) Eye disease (ODSI,d LVQOLe) (37) Sleep apnoea (STOP-Bang,f Cohort 3 only) (5) Medical histories History of disease and medication use (432) Menstrual history (43) Family nistory (28) Healthcare-service utilization (including TCM) (62) Biospecimen for storage Blood samples (whole blood, serum, plasma, white blood cells) (15 ml) Stool samples (20 ml) Hair samples (>0.25 g) Toenails (>0.5 g) Nested-omics cohort (N = 250) Microbiome Metabolomics Anthropometrics (number of measurements) Standing height height bone mineral (DXA) bone mineral (DXA) Blood rate Eye Traditional Chinese medicine diagnosis Abdominal ultrasound 3 only) blood Blood Quality of The well-being Physical The blood and Dual-energy X-ray WELL-China baseline data components Basic information (demographics, socio-economics) (69) Stanford WELL for Life Scale (SWLS) (76) Quality of life (EQ-5D-5L,a WHO-5,b Ruler Scale) (12) Lifestyle behaviours Smoking (20) Alcohol drinking (8) Coffee, tea, water (9) Physical activity (IPAQc) (15) Self-reported anthropometrics and body image (13) Pittsburg Sleep Quality Index (12) Eating habit (34) 26-item food frequency (52) Gastroenterological symptoms (15) Traditional Chinese medicine (TCM) body constitution (54) Eye disease (ODSI,d LVQOLe) (37) Sleep apnoea (STOP-Bang,f Cohort 3 only) (5) Medical histories History of disease and medication use (432) Menstrual history (43) Family nistory (28) Healthcare-service utilization (including TCM) (62) Biospecimen for storage Blood samples (whole blood, serum, plasma, white blood cells) (15 ml) Stool samples (20 ml) Hair samples (>0.25 g) Toenails (>0.5 g) Nested-omics cohort (N = 250) Microbiome Metabolomics Anthropometrics (number of measurements) Standing height height bone mineral (DXA) bone mineral (DXA) Blood rate Eye Traditional Chinese medicine diagnosis Abdominal ultrasound 3 only) blood Blood Basic information (demographics, socio-economics) (69) Stanford WELL for Life Scale (SWLS) (76) Quality of life (EQ-5D-5L,a WHO-5,b Ruler Scale) (12) Lifestyle behaviours Smoking (20) Alcohol drinking (8) Coffee, tea, water (9) Physical activity (IPAQc) (15) Self-reported anthropometrics and body image (13) Pittsburg Sleep Quality Index (12) Eating habit (34) 26-item food frequency (52) Gastroenterological symptoms (15) Traditional Chinese medicine (TCM) body constitution (54) Eye disease (ODSI,d LVQOLe) (37) Sleep apnoea (STOP-Bang,f Cohort 3 only) (5) Medical histories History of disease and medication use (432) Menstrual history (43) Family nistory (28) Healthcare-service utilization (including TCM) (62) Biospecimen for storage Blood samples (whole blood, serum, plasma, white blood cells) (15 ml) Stool samples (20 ml) Hair samples (>0.25 g) Toenails (>0.5 g) Nested-omics cohort (N = 250) Microbiome Metabolomics Anthropometrics (number of measurements) Standing height height bone mineral (DXA) bone mineral (DXA) Blood rate Eye Traditional Chinese medicine diagnosis Abdominal ultrasound 3 only) blood Blood Quality of The well-being Physical The blood and Dual-energy X-ray We surveys on using an developed The survey Table 2 the modules included in the basic demographics and lifestyle behaviours and medical the survey also included conditions and future and we used surveys that either have standard or had been or in studies. For for the we the Physical and used the Sleep Quality Index and to assess and on drinking and were from the China and and dietary was using the developed by University in modules were from the China The Index and were used to for eye diseases and assess eye Quality of life was measured using and the Well-being Index The questionnaire was from the China and with the of the Stanford WELL for Life the survey also included the Stanford WELL for Life Scale (SWLS) to assess well-being and The of well-being has been into different for cultural The Chinese 10 well-being including social lifestyle and experience of and physical purpose and of and and and and were identified using a of in each The and of the are In addition to for each we developed an that to each of the questions in the 10 into 1 overall of the and are unique of the survey data is the of body constitution by traditional Chinese medicine using the constitution refers to a of mental conditions and physical The nine body Blood and The has been in nine in examinations are in Table including and and and were measured scans body composition and bone density. is of the to assess body and bone density. the of abdominal in the Chinese population has over in we abdominal ultrasound to the last participants for of fatty liver disease. important and unique is the inclusion of comprehensive ophthalmology tests, and We collected of blood, stool, and blood ml) was collected and of each blood sample was into blood white blood and Stool samples were collected either the or the of the physical was to their samples into two Hair samples were taken from three different total samples were collected from all 10 Hair and nail samples were at blood and samples were at samples were used to measure for all participants who had provided blood As shown in Table to a complete blood count, liver renal and lipid are of conditions as and In a study of 250 individuals, we measured microbiome via and metabolomics profile by and selected lifestyle behaviours are shown in the of Table 1. and women had similar (Figure which closely across of the for and and Figure that individuals in age groups to have in and patterns were more for three of and social However, the and had in age WELL-China well-being score score by average score by age Of the 10 268 participants at baseline, the of was in men but in women were as to be women drinking is more common drinking of the participants yogurt or other with women more men. participants using of the participants had with more women men disease outcomes and are included in Table We used body to define and standard to define abdominal for for of the men and of the women were but more of the participants were in men and in The of abdominal was in men and in women. WELL-China anthropometrics, disease and by sex NAs refers to participants missing the corresponding variable. SD refers to the standard deviation of the measured Dual-energy X-ray WELL-China anthropometrics, disease and by sex NAs refers to participants missing the corresponding variable. SD refers to the standard deviation of the measured Dual-energy X-ray We defined based on the criteria for the Chinese population and 2 and based on The of measured 2 and was and which is the We also a of eye disease in men and women. the were in To date, three have been using the WELL-China data, including on the non-alcoholic fatty liver disease and eye disease and The microbiome identified two unique microbial with by in men and We also an of eye disease with The study showed that the by was with using the USA In addition to these ongoing as between body and well-being metabolomic and the with gut microbiome and between dietary patterns and microbial and between and eye disease. WELL-China has been to be the large-scale longitudinal study with a on well-being. As is an cohort with a to as a platform for rapid recruitment for future intervention studies as well as the community and individuals in provides unique to effective strategies at the community and the into to the Chinese The use of the novel permits the investigation of and patterns of well-being in a large population and the comprehensive collection of survey data and samples the of social and of well-being and the of As WELL studies other sites in the Bay Area, and with 000 participants enrolled in the overall as of In we to have nearly 40 000 individuals in WELL the study all of are prospective that have the same protocol to define and individual well-being studies across different and racial-ethnic groups will be which will into the of well-being, its and consequences in a global and study from the other three sites will be the baseline recruitment is One of the WELL-China study is that active follow-up will be years from their However, the be on is and of the registered residents in the two districts, we an of individuals for a total of individuals to We will the in active of the WELL-China study the of data digital health and objective environmental information. are considered the to physical and several environmental We are currently in the planning of to a of participants. We to the environmental of the WELL-China study in The WELL-China study welcomes collaborations globally. To the data, are to submit an ancillary study including a research proposal, requested variables and biospecimen and application will be by the WELL will be to with the in the are to contact the via [email protected] (the USA-based PI) or [email protected] (the China-based PI). Supplementary data are available at IJE online. We all WELL-China participants for their time and to this study. We also all the fieldworkers from Zhejiang social workers from each sampled community and from both Zhejiang University of and Stanford Prevention Research Center for their study has been by the at Stanford University protocol number and Zhejiang University protocol number for the Stanford Living laboratory was provided by via an through the to Stanford Zhejiang the and Zhejiang University also provided important support for the study.

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