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Zheng et al1 reported the first genome-wide association study (GWAS) to identify genetic risk factors of haemorrhoidal disease (HEM). In the study, the authors observed that HEM patients had a higher incidence of gastrointestinal domains, particularly diverticular disease and irritable bowel syndrome (IBS). Subsequently, they concluded the standpoint by analysing healthcare records, diagnoses and medication datasets. Nevertheless, such associations reported in the epidemiological study are often unreliable estimates of causal effects and can be interfered with by confounding or other forms of bias.2 To evaluate the causality of HEM on diverticular disease and IBS more accurately, we conducted an in-depth statistical analysis based on two-sample Mendelian randomisation (MR).
Different from the conventional observational study, MR analysis treated genetic variants as instrumental variables (IVs) for exposures, effectively minimising potential bias caused by confounding and reverse causation3 (figure 1A). Genetic variants for investigating the causal effects of HEM (Ncase=218 920, Ncontrol=725 213) on diverticular …
ZZ and XC contributed equally.
Contributors All authors made significant contributions: ZZ and LC designed research; XC, SZ, and CW performed research; and ZZ and XC wrote the paper.
Funding This work was supported by the Tou-Yan Innovation Team Program of the Heilongjiang Province (2019-15), National Natural Science Foundation of China (62222104, 62172130, 61871160), and Heilongjiang Postdoctoral Fund (LBH-Q20030).
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.