Natalija Novokmet

Glycans Are a Novel Biomarker of Chronological and Biological Ages

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 Statement Glycosylation 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.

Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia

A genome‐wide association study of serum uric acid (SUA) laevels 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 single nucleotide polymorphisms (SNPs) in 1300 samples after adjusting for age and gender. Our study replicated four previously reported SUA 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, 35.76 μmol/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 nonsynonymous SNP, rs16890979 (P= 2.24×10−17), a putative causal variant for SUA 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.

Finding Missing Heritability in Less Significant Loci and Allelic Heterogeneity: Genetic Variation in Human Height

Genome-wide association studies (GWAS) have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of ‘missing’ heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus. Using a novel analytical approach we examined allelic heterogeneity of height-associated loci selected from SNPs of different significance levels based on the summary data of the GIANT (stage 1) studies. In a sample of 1,304 individuals collected from an island population of the Adriatic coast of Croatia, we assessed the extent of height variance explained by incorporating the effects of less significant height loci and multiple effective SNPs at the same loci. Our results indicate that approximately half of the 118 loci that achieved stringent genome-wide significance (p-value<5×10−8) showed evidence of allelic heterogeneity. Additionally, including less significant loci (i.e., p-value<5×10−4) and accounting for effects of allelic heterogeneity substantially improved the variance explained in height.

Extent of Height Variability Explained by Known Height-Associated Genetic Variants in an Isolated Population of the Adriatic Coast of Croatia

Background Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2∼10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia. Methodology/Principal Findings In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20∼50 SNPs reported by the remaining individual GWA studies explained 3∼5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent. Conclusions/Significance We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent.

Modeling metabolic syndrome through structural equations of metabolic traits, comorbid diseases, and GWAS variants.

To provide a quantitative map of relationships between metabolic traits, genome‐wide association studies (GWAS) variants, metabolic syndrome (MetS), and metabolic diseases through factor analysis and structural equation modeling (SEM).

Genetic polymorphisms of 15 STR loci in the population of the island of Cres (Croatia)

Background: The population of the island of Cres presents one of the few persisting Eastern Adriatic isolates and is thereby suitable for human population differentiation analyses. Aim: The aim of this study was to analyse the genetic structure of the island of Cres with respect to its eight sub-populations and to compare the genetic variation of the island of Cres with other Eastern Adriatic islands and the Croatian mainland. Subjects and methods: Fifteen AmpFlSTR identifiler loci were analysed in a sample group of 122 unrelated autochthonous individuals from the island of Cres, Croatia. Results: Analysis of STR polymorphisms revealed genetic homogeneity among sub-populations of the island of Cres and small but significant levels of genetic heterogeneity among geographically distant Eastern Adriatic islands. Conclusion: Despite a considerable degree of genetic homogeneity among the studied Eastern Adriatic islands, small but significant differentiation between distant islands indicates geographic sub-structuring which follows the isolation by distance model. This study is supportive of the notion that STR markers are useful for genetic differentiation between larger and geographically more distant regions.

Genetic heritage of Croatians in the Southeastern European gene pool—Y chromosome analysis of the Croatian continental and Island population

The research objective of this study is to enlarge and deepen the Y chromosome research on the Croatian population and enable additional insights into the population diversity and historic events that shaped the current genetic landscape of Croatia and Southeastern Europe (SEE).

Utječe li bračno stanje na doživljeni stres i mentalnu čvrstoću kod studenata sestrinstva i kriminalistike

Au tor za ko res pon den ci ju/Corresponding aut hor: Joško Sindik, PhD, Institute for Anthropological Research, Ljudevita Gaja 32, 10000 Zagreb, Croatia • Phone: +385-1-55 35 122 • Fax: +385-1-55 35 105 • E-mail: josko.sindik@inantro.hr Received February 14th 2014; Accepted February 16th 2014; Utječe li bračno stanje na doživljeni stres i mentalnu čvrstoću kod studenata sestrinstva i kriminalistike?

Some issues of belief in a justice in the world of health workers

Vjerovanje u pravedan svijet (u daljnjem tekstu VUPS) predstavlja nasu želju da je svijet u nacelu pravedno mjesto. Pravda je shvacena na nacin reciprociteta: svatko dobije sto zaslužuje. Dobrim ljudima se stoga ne događaju lose stvari, ali se losim ljudima događaju lose. Dobra djela uvijek ce biti nagrađena, a losa kažnjena. Vjerovanje u pravednost svijeta jedno je od fundamentalnih vjerovanja, koje pojedincu pruža osjecaj sigurnosti, mogucnosti kontrole i predviđanja događaja u svijetu u kojem živi. Ovo je jedna vrsta obrambenog mehanizma: nastoji se objasniti da se lose stvari događaju s nekom svrhom, u protivnom kad bi se događale slucajno (tj. kad bi svatko mogao postati žrtva), to bi donijelo previse tjeskobe u život. VUPS svakako doprinosi dobrobiti i zdravlju pojedinca. Gledajuci kroz sestrinstvo, pacijentova potreba za vjerovanjem u pravedan svijet svakako bi se trebala ocitovati kroz istinsku volju za zdravim i kvalitetnim životom. Cilj istraživanja bio je utvrditi postoji li razlika vjerovanja u pravedan svijet između studenata sestrinstva Zagreba i Dubrovnika. Ispitanici su polaznici III godine studija Sestrinstva u Dubrovniku i II godine studija Sestrinstva u Zagrebu. U ovom istraživanju iskusana je upotrebljivost skracene hrvatske verzije upitnika Cubele i Jurkin iz 2010. Iz izvornog upitnika odabrali smo ukupno 6 tvrdnji (cestica), od kojih tri cestice upitnika opisuju imanentnu a tri ultimativnu pravdu. Utvrdili smo da ne postoje statisticki znacajne razlike VUPS u odnosu na mjesto studiranja studenata Zagreba i studenata Dubrovnika. Također, nasa pretpostavka da su mlađe osobe sklonije imanentnoj pravdi pokazala se netocnom. Ne postoji razlika između osoba s vise i manje godina radnog staža, kao ni razlika u odnosu na bracno stanje.

Some issues of belief in a just world of health workers

Vjerovanje u pravedan svijet (u daljnjem tekstu VUPS) predstavlja nasu želju da je svijet u nacelu pravedno mjesto. Pravda je shvacena na nacin reciprociteta: svatko dobije sto zaslužuje. Dobrim ljudima se stoga ne događaju lose stvari, ali se losim ljudima događaju lose. Dobra djela uvijek ce biti nagrađena, a losa kažnjena. Vjerovanje u pravednost svijeta jedno je od fundamentalnih vjerovanja, koje pojedincu pruža osjecaj sigurnosti, mogucnosti kontrole i predviđanja događaja u svijetu u kojem živi. Ovo je jedna vrsta obrambenog mehanizma: nastoji se objasniti da se lose stvari događaju s nekom svrhom, u protivnom kad bi se događale slucajno (tj. kad bi svatko mogao postati žrtva), to bi donijelo previse tjeskobe u život. VUPS svakako doprinosi dobrobiti i zdravlju pojedinca. Gledajuci kroz sestrinstvo, pacijentova potreba za vjerovanjem u pravedan svijet svakako bi se trebala ocitovati kroz istinsku volju za zdravim i kvalitetnim životom. Cilj istraživanja bio je utvrditi postoji li razlika vjerovanja u pravedan svijet između studenata sestrinstva Zagreba i Dubrovnika. Ispitanici su polaznici III godine studija Sestrinstva u Dubrovniku i II godine studija Sestrinstva u Zagrebu. U ovom istraživanju iskusana je upotrebljivost skracene hrvatske verzije upitnika Cubele i Jurkin iz 2010. Iz izvornog upitnika odabrali smo ukupno 6 tvrdnji (cestica), od kojih tri cestice upitnika opisuju imanentnu a tri ultimativnu pravdu. Utvrdili smo da ne postoje statisticki znacajne razlike VUPS u odnosu na mjesto studiranja studenata Zagreba i studenata Dubrovnika. Također, nasa pretpostavka da su mlađe osobe sklonije imanentnoj pravdi pokazala se netocnom. Ne postoji razlika između osoba s vise i manje godina radnog staža, kao ni razlika u odnosu na bracno stanje.