we 18 test relationships between 1,468 Olink protein levels and the incidence of 23 age-related diseases and 19 mortality, over 16 years of electronic health linkage in the UK Biobank (N=47,600).
Fifty-four proteins had associations with eight or more incident morbidities (Fig. 2b); in all instances, 116 elevated levels of the proteins were associated with the increased incidence of disease or death (i.e. 117 HR > 1). Of the 54 proteins, GDF15 had the largest number of associations (11 incident outcomes), 118 followed by IL6 and PLAUR (10 incident outcomes).
Elevated growth differentiation factor 15 (GDF15), Interleukin-6 (IL6) and 367 plasminogen activator urokinase receptor (PLAUR) had the largest number of associations with 368 incident diseases. This result is in concordance with previous screening of the circulating proteome 369 against multimorbidity and mortality, which identified GDF15 as the top marker of future 370 multimorbidity from 1,301 plasma proteins tested. Further evidence supporting GDF15 as a 371 marker of multiple outcomes including heart disease, type 2 diabetes, stroke, dementia and death has 372 been reported 39–45. IL6 mediates chronic, low-grade inflammation, is a key biomarker of ageing 46 and 373 anti-IL6 therapeutics have been developed for a range of inflammation-associated diseases. While 374 less-extensive evidence exists supporting PLAUR as a biomarker of multiple morbidities, it was 375 associated with incident cancer, cardiovascular disease, diabetes and mortality in previous Cox PH 376 analyses. Similarly, increased levels of neurofilament light (NEFL) were associated with higher 377 incidence of multiple neurological traits (Parkinson’s disease, Alzheimer’s dementia, multiple 378 sclerosis, amyotrophic lateral sclerosis and ischaemic stroke). These diseases are hallmarked by neuron 379 degradation and NEFL may therefore be a consequential marker that is released into the blood upon 380 breakdown of synapses. NEFL was also associated with liver disease, COPD and ischaemic heart 381 disease, which may reflect the presence of underlying synaptic and neuronal dysfunction, or the 382 presence of comorbidities in individuals with these diagnoses.
Discuss! How do we use this information to increase our healthspan?