article published yes Robert F. Hillary author Danni A. Gadd author Daniel L. McCartney author Liu Shi author Archie Campbell author Rosie M. Walker author Craig W. Ritchie author Ian J. Deary author Kathryn L. Evans author Alejo J. Nevado‐Holgado author Caroline Hayward author David J. Porteous author Andrew M. McIntosh author Simon Lovestone author Matthew Richard Robinson author E5D42276-F5DA-11E9-8E24-6303E66974250000-0001-8982-8813 Riccardo E. Marioni author MaRo department Introduction: The levels of many blood proteins are associated with Alzheimer's disease (AD) or its pathological hallmarks. Elucidating the molecular factors that control circulating levels of these proteins may help to identify proteins associated with disease risk mechanisms. Methods: Genome-wide and epigenome-wide studies (nindividuals ≤1064) were performed on plasma levels of 282 AD-associated proteins, identified by a structured literature review. Bayesian penalized regression estimated contributions of genetic and epigenetic variation toward inter-individual differences in plasma protein levels. Mendelian randomization (MR) and co-localization tested associations between proteins and disease-related phenotypes. Results: Sixty-four independent genetic and 26 epigenetic loci were associated with 45 proteins. Novel findings included an association between plasma triggering receptor expressed on myeloid cells 2 (TREM2) levels and a polymorphism and cytosine-phosphate-guanine (CpG) site within the MS4A4A locus. Higher plasma tubulin-specific chaperone A (TBCA) and TREM2 levels were significantly associated with lower AD risk. Discussion: Our data inform the regulation of biomarker levels and their relationships with AD. https://research-explorer.ista.ac.at/download/17076/17356/2023_AlzheimersDementia_Hillary.pdf application/pdfno Wiley2022 eng 2352-8729 3547513710.1002/dad2.12280 141 Hillary, Robert F., et al. “Genome‐ and Epigenome‐wide Studies of Plasma Protein Biomarkers for Alzheimer’s Disease Implicate TBCA and TREM2 in Disease Risk.” <i>Alzheimer’s &#38; Dementia: Diagnosis, Assessment &#38; Disease Monitoring</i>, vol. 14, no. 1, e12280, Wiley, 2022, doi:<a href="https://doi.org/10.1002/dad2.12280">10.1002/dad2.12280</a>. Hillary RF, Gadd DA, McCartney DL, et al. Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer’s disease implicate TBCA and TREM2 in disease risk. <i>Alzheimer’s &#38; Dementia: Diagnosis, Assessment &#38; Disease Monitoring</i>. 2022;14(1). doi:<a href="https://doi.org/10.1002/dad2.12280">10.1002/dad2.12280</a> Hillary RF, Gadd DA, McCartney DL, Shi L, Campbell A, Walker RM, Ritchie CW, Deary IJ, Evans KL, Nevado‐Holgado AJ, Hayward C, Porteous DJ, McIntosh AM, Lovestone S, Robinson MR, Marioni RE. 2022. Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer’s disease implicate TBCA and TREM2 in disease risk. Alzheimer’s &#38; Dementia: Diagnosis, Assessment &#38; Disease Monitoring. 14(1), e12280. R.F. Hillary, D.A. Gadd, D.L. McCartney, L. Shi, A. Campbell, R.M. Walker, C.W. Ritchie, I.J. Deary, K.L. Evans, A.J. Nevado‐Holgado, C. Hayward, D.J. Porteous, A.M. McIntosh, S. Lovestone, M.R. Robinson, R.E. Marioni, Alzheimer’s &#38; Dementia: Diagnosis, Assessment &#38; Disease Monitoring 14 (2022). Hillary, Robert F., Danni A. Gadd, Daniel L. McCartney, Liu Shi, Archie Campbell, Rosie M. Walker, Craig W. Ritchie, et al. “Genome‐ and Epigenome‐wide Studies of Plasma Protein Biomarkers for Alzheimer’s Disease Implicate TBCA and TREM2 in Disease Risk.” <i>Alzheimer’s &#38; Dementia: Diagnosis, Assessment &#38; Disease Monitoring</i>. Wiley, 2022. <a href="https://doi.org/10.1002/dad2.12280">https://doi.org/10.1002/dad2.12280</a>. R. F. Hillary <i>et al.</i>, “Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer’s disease implicate TBCA and TREM2 in disease risk,” <i>Alzheimer’s &#38; Dementia: Diagnosis, Assessment &#38; Disease Monitoring</i>, vol. 14, no. 1. Wiley, 2022. Hillary, R. F., Gadd, D. A., McCartney, D. L., Shi, L., Campbell, A., Walker, R. M., … Marioni, R. E. (2022). Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer’s disease implicate TBCA and TREM2 in disease risk. <i>Alzheimer’s &#38; Dementia: Diagnosis, Assessment &#38; Disease Monitoring</i>. Wiley. <a href="https://doi.org/10.1002/dad2.12280">https://doi.org/10.1002/dad2.12280</a> 170762024-05-29T06:13:25Z2024-07-31T11:33:50Z