Genetic variations in extracellular matrix degradation pathways linking to major depressive disorder: Evidence from a large-scale genetic association study

Halliru Zailani, Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
Daniel Tzu-Li Chen, Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
Sheng-Che Lin, An-Nan Hospital, China Medical University, Tainan, Taiwan.
Jia-Hau Lee, An-Nan Hospital, China Medical University, Tainan, Taiwan
Mei-Ling Li, Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
Jane Pei-Chen Chang, Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
Kuan-Pin Su, Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.Follow

Abstract

Dysregulation of extracellular matrix (ECM) degradation pathways has been increasingly implicated in major depressive disorder (MDD), yet its genetic basis remains unclear. This study investigated the relationship between ECM-related genetic polymorphisms and MDD susceptibility. In a case-control study, we analyzed 317 MDD patients and 1,268 sexmatched controls from the Taiwan Biobank (TWB). Genomic DNA was analyzed using the Affymetrix TWB array, targeting single nucleotide polymorphisms (SNPs) in 140 ECM degradation genes (Reactome database). Full-model association tests identified significant SNPs, validated with 5,000 max(T) permutations and adjusted via logistic regression for age, body mass index, education level, and marital status. We identified 12 SNPs across 10 ECMrelated genes significantly associated with MDD, including ADAM metallopeptidase domain

17 (ADAM17, rs55820761), brevican (BCAN, rs11264511), CD44 molecule (CD44, rs12270356), collagen type XVII alpha 1 chain (COL17A1; rs2282436 and rs10883962), collagen type III alpha 1 chain (COL3A1; rs16830979 and rs10883962), collagen type VI alpha 6 chain (COL6A6, rs16830219), cathepsin L (CTSL, rs2274611), Kallikrein-related peptidase 2 (KLK2, rs2664156), matrix metallopeptidase 11 (MMP11, rs738791), and nicastrin (NCSTN, rs3753391 ). This study provides the first genetic evidence linking ECM degradation pathways to MDD susceptibility, identifying novel biomarkers for early diagnosis and precision therapy. Further research and cross-population studies are needed to confirm these findings.

Recommended Citation

Zailani, Halliru; Chen, Daniel Tzu-Li; Lin, Sheng-Che; Lee, Jia-Hau; Li, Mei-Ling; Chang, Jane Pei-Chen; and Su, Kuan-Pin (2025) "Genetic variations in extracellular matrix degradation pathways linking to major depressive disorder: Evidence from a large-scale genetic association study," BioMedicine: Vol. 15 : Iss. 4 , Article 7.
DOI: 10.37796/2211-8039.1677