ABSTRACT
Background: The large-scale quantitative evidence base to understand and improve health and healthcare outcomes for people who are trans and/or non-binary is still developing, although what research there is suggests that risk of poor health is high, and experiences of healthcare services are often poor. In 2021 the GP Patient Survey, which is carried out annually to measure patient experience in primary care in England, added inclusive questions about gender identity and trans status for the first time. Methods: This protocol paper pre-registers the methods that we will use for this work for a secondary analysis of these data, including both the statistical analysis protocol and early patient and public involvement work, to answer the following three research questions: (1) What are the (a) demographic characteristics, (b) health conditions, and (c) healthcare experiences of trans and/or non-binary adults in England? (2) Was there any difference in whether people who are trans and/or non-binary had been asked to shield during the COVID-19 pandemic or not compared with all other survey responders? (3) Does the relationship between being trans and/or non-binary, and self-reported long-term mental health problems, autism and autistic spectrum disorder and learning disability vary by age, gender, ethnicity, deprivation, sexual orientation or region?
ABSTRACT
Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 × 10-4) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.