RT Journal Article SR Electronic T1 Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202000817 DO 10.26508/lsa.202000817 VO 3 IS 10 A1 Hong, Mun-Gwan A1 Dodig-Crnković, Tea A1 Chen, Xu A1 Drobin, Kimi A1 Lee, Woojoo A1 Wang, Yunzhang A1 Edfors, Fredrik A1 Kotol, David A1 Thomas, Cecilia Engel A1 Sjöberg, Ronald A1 Odeberg, Jacob A1 Hamsten, Anders A1 Silveira, Angela A1 Hall, Per A1 Nilsson, Peter A1 Pawitan, Yudi A1 Uhlén, Mathias A1 Pedersen, Nancy L A1 Hägg, Sara A1 Magnusson, Patrik KE A1 Schwenk, Jochen M YR 2020 UL http://www.life-science-alliance.org/content/3/10/e202000817.abstract AB Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50–92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 × 10−6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12–1.39; P = 6.45 × 10−5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7–9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.