Self-reported Anxiety Sensitivity Index in the TwinsUK cohort

The anxiety sensitivity (AS) construct has received considerable attention in anxiety research and is considered to be a cognitive vulnerability factor for the study of anxiety related disorders. The Anxiety Sensitivity Index (ASI) is the most widely used instrument for the study of AS. The present Data Note provides an overview of all the 16-item ASI questionnaires filled and returned by the twins in the TwinsUK registry. This work does not provide any multidimensional or factor structure analysis of the responses provided. TwinsUK registry encompasses a wide range of clinical and self-reported data that can be used as confounding factors in the study of cognitive and mental health.


Introduction
The Department of Twin Research and Genetic Epidemiology at St. Thomas' Hospital, King's College London (KCL), hosts the UK's largest adult twin registry (or TwinsUK) 1 . Twin-sUK is a cohort of volunteer adult twins currently consisting of 14,575 monozygotic (MZ) and dizygotic (DZ) twins with ages between 18 to 101 years. The Registry includes self-reported and clinical data that has been measured longitudinally for majority of volunteers through comprehensive visits, annual questionnaires, and several project-led studies.
Over 69% of the registered twins have attended at least one comprehensive clinical assessment and about half of those undergone at least two follow up health visits. The primary aim of TwinUK studies have been the genetic basis of complex diseases, such as cardiovascular, metabolic, musculoskeletal, and ophthalmologic diseases. Between 1992 and 2004, active twins were invited and attended a comprehensive 'baseline' visit, that was followed by a 1-day clinical visit (first follow-up visit). The first follow up visit aimed to discover the genetics of common disease and complex traits. The focus of the study then broadened to include the complex healthy ageing process and the genetic and lifestyle factors that influence aging over time (the Healthy Aging Twin Study (HATS)) 2 . The second follow-up visits were part of the HATS study. The third cycle of follow-up visits were carried out between 2012 and 2017 as part of the Biomedical Research Centre (BRC) study, with the aim of understanding genetic and environmental interactions in the development and progression of disease. During the BRC study 5286 volunteers from the TwinsUK registry attended the clinics and over 6300 questionnaires were returned.
All visits followed a similar layout. Prior to each visit, participants were asked to complete a general questionnaire focused on recent self-reposted clinical findings as well as behavior, and lifestyle related question. Blood and urine samples were also collected during the visits. Furthermore, a number of other tests such as weight, height, blood pressure, grip strength, and biochemical levels were measured. Cognitive tests such as Cambridge Neuropsychological Test Automated Battery (CANTAB) 3 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 for a subset of the cohort. The following sections of this document will provide the overlap number between the participants with both 'omics' and Anxiety Sensitivity Index (ASI) data.
Here, we present an overview of 16-item ASI questionnaires 4 that were completed and returned by the volunteers in the Twin-sUK cohort over time. The registry incorporates a wide range of other longitudinal data including different self-reported and clinical cognitive data such as the Hospital Anxiety and Depression Scale (HADS) 5 , and self-reported anxiety and depression diagnosis. These can be used by the scientific community, where relevant, to provide a more comprehensive research outcome.
We collected data on depression, anxiety, and anxiety sensitivity in the TwinsUK cohort in order to understand the genetic epidemiology of these traits and their link to other health related phenotypes available on the registry. These data are intended to enhance the health phenotyping in this population for the benefit of the scientific community and the public.

Method
As conceptualized by Reiss and his colleagues 2 , anxiety sensitivity (AS) refers to the fear of anxiety-related physical sensations, which arise from the belief that these sensations can have harmful physical, psychological, or social consequences. The 16 item Anxiety Sensitivity Index (ASI) questionnaire is the most widely used assessment for anxiety sensitivity (AS).
A total of 8328 ASI questionnaires have been collected at the department of TwinsUK from which 57.6% (N=4802) were sent and completed in 2005 as part of the TwinsUK annual questionnaire (Twins Questionnaire (2005)), while 42.4% (N=3526) were sent to the twins and returned between 2007 and 2010 as part of the HATS personality questionnaire included in the visit packs. The age of response ranged from 18 to 87, with 93.6% of respondents female.
The questionnaires were administered on paper and they were manually entered by data operators. More than half of the participants (N= 4912; 58.8%) have two time points in which they have completed and returned ASI questionnaire, across a 5-year time frame. The ASI items are listed below, alongside their TwinsUK variable code.

DN00001.
It is important to me not to appear nervous (Table 1).
DN00002: when I cannot keep my mind on a task, I worry that I might be going crazy ( Table 2).

DN000004.
It scares me when I feel faint (Table 4).

DN000005.
It is important to me to stay in control of my emotions (Table 5). (Table 6). (Table 7).

DN000008.
It scares me when I am nauseous (Table 8).
DN000009. When I notice that my heart is beating rapidly, I worry that I might have a heart attack (Table 9).
DN000010. It scares me when I become short of breath (Table 10).

DN000011.
When my stomach is upset, I worry that I might be seriously ill (Table 11).
DN000012. It scares me when I am unable to keep my mind on a task (Table 12).

DN000013.
Other people notice when I feel shaky (Table 13).

DN000015.
When I am nervous, I worry that I might be mentally ill (Table 15).

DN000016.
It scares me when I am nervous (Table 16).
This 16-item scale asks participants to indicate how much they are affected by each of the items that can be divided into three categories of mental incapacitation concerns, social concerns, and physical concerns. These three factors together can all form an overall AS factor.

Scoring system
The respondent is required to rate each item by selecting one of five responses. Each item is rated on a five-point Likert scale ranging from 0 (very little) to 4 (very much). An individual's AS score is the sum of the scores on the 16 items.
Researchers use a variety of factor-based approaches in the analysis of ASI data. These are not summarized here, thought the overall characteristics of the sample are presented in Table 18 as a total ASI score.

Omics data
Anxiety sensitivity has been linked to different forms of psychopathology, such as anxiety disorder, chronic pain, and substance abuse. TwinsUK has collected data on some of the potential confounding factors such as age, BMI, smoking, alcohol consumption, and chronic pain that can be provided to the research community by following the instructions listed in the Data availability section below. Furthermore, TwinsUK holds a wide range of 'omics' data for subsections of its samples. Table 19 provides the overlap number of participants with available 'omics' data.

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 (grants 079771 and 081878).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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