Proteins detected in plasma using proximity extension assay

Proximity extension assays (PEA) based on Olink was performed for 5279 proteins across two longitudinal cohorts. The first cohort is a wellness study covering 76 individuals sampled over two years, with 5 vistis. The second cohort consists of a birth cohort that follows 100 individuals from infancy into adulthood, with visits at years 4, 8, 16, and 22. Relative protein abundance is reported as Normalized Protein eXpression (NPX) for the corresponding geners, separately for males and females.

To understand the sources of variation in protein levels, mixed effects models were fitted for each protein in both datasets. These models included subject as a random effect, and age and sex as fized effects (further details in Methods). From these models, we estimated the proportion of variation explained by individual-specific effects versus age- or sex-related effects.

Proteins with a high proportion of variance explained by the random effect or subject are generally stable within individuals but vary across the population, reflecting personal baseline differences. Proteins with a high proportion of variance explained by fixed effects show clar patterns related to age or sex, highlighting proteins infleunced by biological factors rather than individual baseline differences.

Childhood

Gene Gene description % explained variance
- fixed effects
% explained variance
- random effects
AMBN Ameloblastin 84.04 0.56
CCN5 Cellular communication network factor 5 82.75 1.46
KLK4 Kallikrein related peptidase 4 82.52 6.09
PTPRN Protein tyrosine phosphatase receptor type N 82.25 5.43
TAFA1 TAFA chemokine like family member 1 80.18 4.88
COL9A1 Collagen type IX alpha 1 chain 79.73 0.53
MS4A1 Membrane spanning 4-domains A1 79.47 5.30
CES2 Carboxylesterase 2 78.65 0.87
COL2A1 Collagen type II alpha 1 chain 77.96 1.70
BSG Basigin (Ok blood group) 77.82 4.22
PTPRR Protein tyrosine phosphatase receptor type R 77.36 8.18
SEZ6 Seizure related 6 homolog 77.29 7.34
NELL2 Neural EGFL like 2 77.29 11.60
MATN3 Matrilin 3 76.90 0.00
IGFBP6 Insulin like growth factor binding protein 6 76.78 2.67
ACAN Aggrecan 76.73 0.30
ODAM Odontogenic, ameloblast associated 75.77 4.59
SEZ6L Seizure related 6 homolog like 75.66 7.69
VWC2L Von Willebrand factor C domain containing 2 like 73.99 0.00
DSPP Dentin sialophosphoprotein 72.96 0.00
SEMA4C Semaphorin 4C 71.98 0.00
MSLN Mesothelin 70.95 6.47
ALK ALK receptor tyrosine kinase 70.47 5.43
MMP3 Matrix metallopeptidase 3 70.45 0.00
PRELP Proline and arginine rich end leucine rich repeat protein 70.31 8.17
PROK1 Prokineticin 1 70.28 7.27
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Adult

Gene Gene description % explained variance
- fixed effects
% explained variance
- random effects
SPINT3 Serine peptidase inhibitor, Kunitz type 3 85.98 6.89
INSL3 Insulin like 3 85.21 6.96
EDDM3B Epididymal protein 3B 84.41 10.49
FSHB Follicle stimulating hormone subunit beta 77.83 16.06
TEX101 Testis expressed 101 68.49 25.76
ACRV1 Acrosomal vesicle protein 1 62.33 25.25
PROK1 Prokineticin 1 53.30 34.83
PSPN Persephin 48.44 41.81
NPTX2 Neuronal pentraxin 2 38.09 45.27
LEP Leptin 36.21 51.02
MMP3 Matrix metallopeptidase 3 35.42 47.56
OBP2B Odorant binding protein 2B 33.98 58.51
FABP4 Fatty acid binding protein 4 33.77 45.87
LYZL2 Lysozyme like 2 33.06 27.02
SPRR3 Small proline rich protein 3 30.91 36.22
ENPP2 Ectonucleotide pyrophosphatase/phosphodiesterase 2 30.10 34.86
EDA2R Ectodysplasin A2 receptor 27.97 56.73
GH1 Growth hormone 1 25.74 35.35
LPL Lipoprotein lipase 25.62 36.67
CRISP2 Cysteine rich secretory protein 2 25.25 70.17
LHB Luteinizing hormone subunit beta 25.09 53.30
IL1RL1 Interleukin 1 receptor like 1 24.03 52.42
ANGPTL3 Angiopoietin like 3 23.62 32.97
OGN Osteoglycin 23.32 50.48
ALCAM Activated leukocyte cell adhesion molecule 23.21 32.57
SERPINA11 Serpin family A member 11 22.89 55.99
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