An overview of the TwinsUK cohort ’ s anxiety and depression assessment , using the self-reported Hospital Anxiety and Depression Scale

Anxiety and depression are common mental health conditions that frequently coexist. The Hospital Anxiety and Depression (HADS) questionnaire, is a widely used questionnaire, both in the clinic and in research. HADS provides an assessment of anxiety and depression based on non-physical symptoms, hence it can be used in patients with other physical pain and symptoms. This resource provides an overview of all the HADS questionnaires completed by the twins in the TwinsUK registry. This includes both monozygotic and dizygotic twins, over a wide range of age and socioeconomic backgrounds. TwinsUK holds a wide range of phenotype and genotyping data that can be used as confounding factors in the study of mental health.


Introduction
The UK Adult Twin Registry (or TwinsUK) is a cohort of volunteer adult twins currently consisting of 14,575 adult twins (55% monozygotic and 43% dizygotic) aged between 18 to 101 years from around the United Kingdom 1 . The registry was started in 1992 through media campaigns targeted at middleaged women to allow the investigation of osteoporosis and osteoarthritis. The success of early studies led to the expansion of the registry, and it now incorporates both male and female twins with a range of clinical and behavioral phenotypes as well as genotyping data.
The Department of Twin Research and Genetic Epidemiology at St. Thomas' Hospital, King's College London hosts the registry. The primary focus of study has been the genetic basis of complex diseases (cardiovascular, metabolic, musculoskeletal, and ophthalmologic diseases), which has broadened to include the complex healthy ageing process. The registry includes selfreported and clinical data that has been measured longitudinally for majority of volunteers through comprehensive visits, annual questionnaires, and several project-led studies. Figure 1 gives an overview of the primary and the first two follow-up visits in the TwinsUK cohort.
The second follow-up visits were part of the Healthy Aging Twin study that examined genetic and lifestyle factors that influence ageing over time. This was followed by a third cycle of follow up visits carried out between 2012 and 2017 in which 5286 individuals attended the clinics as part of the Biomedical Research Centre (BRC) study with volunteers from the Twin-sUK registry, and over 6300 questionnaires were returned. The BRC study had aimed to understand the interactions between genes and environment in disease processes.
Here, we present the key variables available on this cohort with respect to depression and anxiety for use by the scientific community. The registry incorporates a range of other longitudinal data based on different self-reported questionnaires, follow up visits, and multi-omics assays, which can be combined with the dataset described. In total, 6432 of the individuals in the registry have at least one or more follow-up visit, with a mean follow-up time of 5.98 years. The general format of the visits were similar, and in all visits blood and urine samples were collected. Prior to the visits, participants completed a questionnaire focused on lifestyle, behavior, and a number of recent self-reported clinical findings. During the visits, a number of other tests, such as weight, height, blood pressure, grip strength, and biochemical levels, were measured. Cognitive tests such as the Cambridge Neuropsychological Test Automated Battery (CANTAB) 2 were also performed in a subset of visits. As well as the self-reported and measured phenotypes mentioned above, TwinsUK also benefits from a number of genotyping and 'omics' data. These results are only available for a subsection of cohort. In the following sections of this document the overlap between the 'omics' data and the HADS responses are provided.
We collected data on depression, anxiety and anxiety sensitivity in the TwinsUK population in order to understand the genetic epidemiology of these traits and their relation to other health related phenotypes and multi-omic measures collected on the cohort. These data are intended to enhance the health phenotyping in this population for the benefit of the scientific community and the public.

Methods
The Hospital Anxiety and Depression Scale (HADS) was devised by Zigmond and Snaith 3 . It is a 14-item scale used to detect the level of anxiety and depression in a medical outpatient clinic setting. The HADS scale was included in the annual DTR Twin Health questionnaire in 2006 and more recently it has been sent to the twins as a supplement to the Baseline Health Questionnaire in 2017.
The completed and returned questionnaires from both batches have been merged and the data is presented in this dataset. Overall a total of 9227 questionnaires have been completed and returned from which 5169 were returned in 2006 and 4058 in 2017.
A total of 2470 individuals have more than one response time point while the rest only completed the questionnaire in one occasion. The majority of respondents (87.9%; N f =5940) were female and 12.1% (N m =814) were male.
The 14 items are listed below: Q7_162. I feel tense or wound up (Table 1).
Q7_163. I still enjoy the things I used to enjoy ( Table 2).
Q7_164. I get a sort of frightened feeling as if something awful is about to happen (Table 3).
Q7_165. I can laugh and see the funny side of things (Table 4).
Q7_168. I can sit at ease and feel relaxed (Table 7).
Q7_169. I feel as if I am slowed down (Table 8).  Q7_170. I get a sort of frightened feeling like butterflies in my stomach (Table 9).
Q7_171. I have lost interest in my appearance (Table 10).
Q7_172. I feel restless as if I have to be on the move (Table 11).
Q7_173. I look forward with enjoyment to things (Table 12).
Q7_175. I can enjoy a good book or radio, TV programme (Table 14).       The total number of valid and missing responses for each phenotype is provided in Table 15.

Scoring system
The respondent is required to rate each item by selecting one of four responses (0, 1, 2, and 3). The score for anxiety and depression is calculated separately. An individual's anxiety score is the sum of the scores on the anxiety related items and his/her depression score is the sum of depression-relate items. Table 16. provides the HADS scoring as well as the mean age and the male to female ratio amongst the respondents.

Omics data
TwinsUK registry hosts a variety of clinical and self-reported phenotypes that can be used as confounding factors alongside the HADS dataset depending on the research project, some of these include, socioeconomic data, smoking, alcohol, and a number of cognitive phenotypes. Furthermore, there are a number of genetic, epigenetic, and 'omics' data that are available for subsets of participants. Table 17 gives the number overlap between the participants in this dataset and their omics data where available.

Data availability
TwinsUK facilitates and encourages the sharing of data with the scientific community to further scientific research. Researchers can follow the below steps to request and access the datasets provided on this data note as well as other TwinsUK data. All the datasets included in this data note can be accessed by quoting the data note name or specific variable codes provided within this report. 1. Please search for your required phenotype using the TwinsUK Phenotype spreadsheet containing a list of all TwinsUK phenotypes.
2. Please read the TwinsUK Data Access Policy document which describes the process of accessing the data and samples as well as the costs associated.
3. Please submit your Proposal Form to the TwinsUK Resource Executive Committee (TREC) for consideration. You will be notified of the outcome of the review within three weeks and advised on the next stage.
The proposal form should specify the data and/or samples required including individual variables with an appropriate justification describing the aims/hypothesis of the project for which the data is requested. Further information can also be found on the TwinsUK website (www.twinsuk.ac.uk/data-access).
If you have any other enquires related to data access please email Collaborations and Data Access Manager, Victoria Vazquez (victoria.vazquez@kcl.ac.uk).

Grant information
The Wellcome Trust, Medical Research Council, European Commission and National Institute for Health Research (NIHR) provide core funding and Support for the Department of Twin Research and Genetic Epidemiology (Twins UK). The research data provided on this paper was specifically funded by the Wellcome trust (079771 and 202786), and the NIHR Biomedical Research Centres (BRC).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.