Fine structural details of glycans attached to the conserved N-glycosylation site significantly not only affect function of individual immunoglobulin G (IgG) molecules but also mediate inflammation at the systemic level. By analyzing IgG glycosylation in 5,117 individuals from four European populations, we have revealed very complex patterns of changes in IgG glycosylation with age. Several IgG glycans (including FA2B, FA2G2, and FA2BG2) changed considerably with age and the combination of these three glycans can explain up to 58% of variance in chronological age, significantly more than other markers of biological age like telomere lengths. The remaining variance in these glycans strongly correlated with physiological parameters associated with biological age. Thus, IgG glycosylation appears to be closely linked with both chronological and biological ages. Considering the important role of IgG glycans in inflammation, and because the observed changes with age promote inflammation, changes in IgG glycosylation also seem to represent a factor contributing to aging.Significance StatementGlycosylation is the key posttranslational mechanism that regulates function of immunoglobulins, with multiple systemic repercussions to the immune system. Our study of IgG glycosylation in 5,117 individuals from four European populations has revealed very extensive and complex changes in IgG glycosylation with age. The combined index composed of only three glycans explained up to 58% of variance in age, considerably more than other biomarkers of age like telomere lengths. The remaining variance in these glycans strongly correlated with physiological parameters associated with biological age; thus, IgG glycosylation appears to be closely linked with both chronological and biological ages. The ability to measure human biological aging using molecular profiling has practical applications for diverse fields such as disease prevention and treatment, or forensics.

Summary A genome-wide association study of serum uric acid levels was performed in a relatively isolated population of European descent from an island of the Adriatic coast of Croatia. The study sample included 532 unrelated and 768 related individuals from 235 pedigrees. Inflation due to relatedness was controlled by using genomic control. Genetic association was assessed with 2,241,249 SNPs in 1300 samples after adjusting for age and gender. Our study replicated four previously reported serum uric acid loci (SLC2A9, ABCG2, RREB1, and SLC22A12). The strongest association was found with a SNP in SLC2A9 (rs13129697, P=2.33×10−19), which exhibited significant gender-specific effects, 35.76μmol/L (P=2.11×10−19) in females and 19.58 μmol/L (P=5.40×10−5) in males. Within this region of high linkage disequilibrium, we also detected a strong association with a non-synonymous SNP, rs16890979 (P=2.24×10−17), a putative causal variant for serum uric acid variation. In addition, we identified several novel loci suggestive of association with uric acid levels (SEMA5A, TMEM18, SLC28A2, and ODZ2), although the P-values (P<5×10−6) did not reach the threshold of genome-wide significance. Together, these findings provide further confirmation of previously reported uric acid-related genetic variants and highlight suggestive new loci for additional investigation.

High mtDNA variation in Southeastern Europe (SEE) is a reflection of the turbulent and complex demographic history of this area, influenced by gene flow from various parts of Eurasia and a long history of intermixing. Our results of 1035 samples (488 from Croatia, 239 from Bosnia and 130 from Herzegovina, reported earlier, and 97 Slovenians and 81 individuals from Žumberak, reported here for the first time) show that the SEE maternal genetic diversity fits within a broader European maternal genetic landscape. The study also shows that the population of Žumberak, located in the continental part of Croatia, developed some unique mtDNA haplotypes and elevated haplogroup frequencies due to distinctive demographic history and can be considered a moderate genetic isolate. We also report seven samples from the Bosnian population and one Herzegovinian sample designated as X2* individuals that could not be assigned to any of its sublineages (X2a'o) according to the existing X2 phylogeny. In an attempt to clarify the phylogeny of our X2 samples, their mitochondrial DNA has been completely sequenced. We suppose that these lineages are signs of local microdifferentiation processes that occurred in the recent demographic past in this area and could possibly be marked as SEE-specific X2 sublineages.

Maternal nutrition and lifestyle in pregnancy are important modifiable factors for both maternal and offspring’s health. Although the Mediterranean diet has beneficial effects on health, recent studies have shown low adherence in Europe. This study aimed to assess the Mediterranean diet adherence in 266 pregnant women from Dalmatia, Croatia and to investigate their lifestyle habits and regional differences. Adherence to the Mediterranean diet was assessed through two Mediterranean diet scores. Differences in maternal characteristics (diet, education, income, parity, smoking, pre-pregnancy body mass index (BMI), physical activity, contraception) with regards to location and dietary habits were analyzed using the non-parametric Mann–Whitney U test. The machine learning approach was used to reveal other potential non-linear relationships. The results showed that adherence to the Mediterranean diet was low to moderate among the pregnant women in this study, with no significant mainland–island differences. The highest adherence was observed among wealthier women with generally healthier lifestyle choices. The most significant mainland–island differences were observed for lifestyle and socioeconomic factors (income, education, physical activity). The machine learning approach confirmed the findings of the conventional statistical method. We can conclude that adverse socioeconomic and lifestyle conditions were more pronounced in the island population, which, together with the observed non-Mediterranean dietary pattern, calls for more effective intervention strategies.

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