Pathway Association Studies Reveal Gene Loci and Pathway Networks that Associated With Plasma Cystatin C Levels

Hongxiao Jiao; Miaomiao Zhang; Yuan Zhang; Yaogang Wang; Wei-Dong Li

doi:10.3389/fgene.2021.711155

Pathway Association Studies Reveal Gene Loci and Pathway Networks that Associated With Plasma Cystatin C Levels

Front Genet. 2021 Nov 25:12:711155. doi: 10.3389/fgene.2021.711155. eCollection 2021.

Authors

Hongxiao Jiao¹, Miaomiao Zhang², Yuan Zhang^{2

3}, Yaogang Wang³, Wei-Dong Li²

Affiliations

¹ Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
² Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
³ College of Public Health, Tianjin Medical University, Tianjin, China.

Abstract

As a marker for glomerular filtration, plasma cystatin C level is used to evaluate kidney function. To decipher genetic factors that control the plasma cystatin C level, we performed genome-wide association and pathway association studies using United Kingdom Biobank data. One hundred fifteen loci yielded p values less than 1 × 10^-100, three genes (clusters) showed the most significant associations, including the CST8-CST9 cluster on chromosome 20, the SH2B3-ATXN2 gene region on chromosome 12, and the SHROOM3-CCDC158 gene region on chromosome 4. In pathway association studies, forty significant pathways had FDR (false discovery rate) and or FWER (family-wise error rate) ≤ 0.001: spermatogenesis, leukocyte trans-endothelial migration, cell adhesion, glycoprotein, membrane lipid, steroid metabolic process, and insulin signaling pathways were among the most significant pathways that associated with the plasma cystatin C levels. We also performed Genome-wide association studies for eGFR, top associated genes were largely overlapped with those for cystatin C.

Keywords: United Kingdom biobank; cystatin C; genetics; genome wide association; pathway association studies.