SNP rs7549881, near SGIP1 at 1p31.3, is significantly associated with digestive disorders and Parkinsonism in women.

BACKGROUND

SGIP1 (SH3GL Interacting Endocytic Adaptor 1) at 1p31.3 has been implicated in early-onset Parkinsonism in a rare familial case. We investigated the nearby intronic SNP rs7549881 (A > G, MAF 0.43) for association with Parkinson's disease (PD) and other traits in the UK Biobank.

METHODS

A total of 385,629 UK Biobank participants with ≥7 years of education were included. Logistic regression adjusted for age, sex, smoking, and constipation evaluated the association between rs7549881 and PD. PheWAS was performed using PheWeb to identify additional phenotypic associations.

RESULTS

Among females, 26.0 % of rs7549881 GG homozygotes had PD, compared to 22.2 % without PD (p = 0.004). No significant genotype-PD association was observed in males. Logistic regression showed that age (OR 1.14), male sex (OR 1.83), and constipation (OR 4.73) increased PD risk, while smoking was protective (OR 0.75). GG genotype conferred increased PD risk versus AA (OR 1.21, p = 0.015). PheWAS identified significant associations with gastrointestinal phenotypes, including functional digestive disorders and noninfectious gastroenteritis.

CONCLUSION

SNP rs7549881 is associated with PD in females and with gastrointestinal disorders across both sexes. These findings reinforce the role of SGIP1 in synaptic endocytosis and suggest its contribution to gut-brain axis dysfunction in PD.