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Glycans and age Dealing with non-linear correlations Lucija Klari ć Genos Ltd. Lucija Klari ć. Relationship between age and glycans. Local correction for age and sex. linear age/sex correction vs local age/sex correction
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Glycans and ageDealing with non-linear correlationsLucijaKlarićGenos Ltd. LucijaKlarić
Local correction for age and sex • linear age/sex correction vs local age/sex correction • local age/sex correction – general additive models with smooth function (R package: mgcv)
Local correction for age and sex Residuals after age and sex correction in Korcula cohort
Local correction for age and sex Residuals after age and sex correction in Korcula cohort
Materials and methods • 2 cohorts: • Korcula • 851 individuals • 316751 SNPs (typed) • 77 glycans (UPLC) • Vis • 808 individuals • 308996 SNPs (typed) • 77 glycans (UPLC) • GWAS – GenABEL package for R • Meta analysis – MetABEL package for R
Concluding remarks • Most p-values are lower in linear correction than local correction for age • Linear age correction outperformes local age correction • possible reason: local correction corrects better only few people (~50 people from 40-50 years of age) • Associations of SNPs and glycans are quite robust • Residuals of local correction for age and sex are not related to age
Monogalactosylated IgG glycans in aging • β4GalT-I (Beta-1,4-galactosyltransferase 1) • adds galactose to GlcNAc residues • interacts preferentially with 1,6-arm FA2[6]G1 FA2[3]G1 FA2B[6]G1 FA2B[3]G1
Monogalactosylated IgG glycans in aging Monogalactosylated structures with Gal on 1,6 arm decrease with age. Monogalactosylated structures with bisecting GlcNAc with Gal on 1,3 or 1,6 arm increase with age.
Monogalactosylated IgG glycans in aging Monogalactosylated structures with Gal on 1,6 arm decrease with age. Monogalactosylated structures with bisecting GlcNAc with Gal on 1,3 or 1,6 arm increase with age. Table 1. Associations of glycans with age (UPLC)
Monogalactosylated IgG glycans in aging Table 2. Correlation of age and glycans measured by different methods in Vis population (500 subjects).