RESUMO
BACKGROUND: Every third child in Croatia is classed as overweight or obese. Infant growth can represent early warning signs for obesity. AIM: To detect early risk factors for obesity by investigating infant size and early growth trajectories and their association with maternal lifestyle and breastfeeding. SUBJECTS AND METHODS: Ninety-eight mother-child pairs from the Croatian Islands' Birth Cohort Study (CRIBS) cohort were included in the study. Data were collected from questionnaires and medical records. Growth data were converted to Z-scores using World Health Organisation (WHO) standards and used as the primary outcome. RESULTS: Z-score trajectories in the first year of life were in line with WHO standards. A direct link between infant size and maternal socioeconomic status (SES) or breastfeeding was not detected. However, child weight gain in the first 6 months was associated with maternal body mass index (BMI) before pregnancy (p < 0.01). A positive association was also established between breastfeeding and maternal SES and mothers that report an unhealthy diet have heavier children (p < 0.05, respectively). CONCLUSION: Infant size and early growth in Croatia is in line with WHO standards and risk factors for obesity development were detectable in the first year of life, but not highly pronounced. However, more effective BMI monitoring and promotion of a healthy diet and lifestyle of women before and during pregnancy is needed.
Assuntos
Aleitamento Materno , Obesidade , Gravidez , Lactente , Humanos , Feminino , Estudos de Coortes , Obesidade/etiologia , Sobrepeso/complicações , Índice de Massa Corporal , Estilo de VidaRESUMO
BACKGROUND: High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are significant risk factors for maternal and neonatal health. AIM: To assess pre-pregnancy BMI and GWG during pregnancy and their association with different maternal and neonatal characteristics in the transitional Mediterranean population from the Eastern Adriatic islands. SUBJECTS AND METHODS: Two hundred and sixty-two mother-child dyads from the CRoatian Islands' Birth Cohort Study (CRIBS) were included in the study. Chi-square test, ANOVA, and regression analysis were used to test the association between selected characteristics. RESULTS: In total, 22% of women entered pregnancy as overweight/obese and 46.6% had excessive GWG. Pre-pregnancy overweight and obesity were significantly associated with elevated triglycerides uric acid levels, and decreased HDL cholesterol in pregnancy. Excessive GWG was associated with elevated fibrinogen and lipoprotein A levels. Women with high pre-pregnancy BMI and GWG values were more likely to give birth to babies that were large for gestational age (LGA), additionally confirmed in the multiple logistic regression model. CONCLUSION: High maternal pre-pregnancy BMI and excessive GWG were both significantly associated with deviated biochemical parameters and neonatal size. More careful monitoring of maternal nutritional status can lead to better pre- and perinatal maternal healthcare.
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Sobrepeso , Saúde Reprodutiva , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Obesidade/epidemiologia , Obesidade/etiologia , Sobrepeso/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Estados Unidos , Aumento de PesoRESUMO
AIM: To use the method of meta-analysis to assess the influence of island population isolation on the sub-structuring of the Croatian population, as well as the influence of regional population groups on the sub-structuring of the Southeastern European population with regard to basic population genetic statistical parameters calculated by using STR locus analysis. METHODS: Bio-statistical analyses were performed for 2877 unrelated participants of both sexes from Southeastern Europe. Nine autosomal STR loci (D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317, and D7S82) were analyzed by using standard F-statistics and population structure analysis (Structure software). RESULTS: Genetic differentiation of Croatian subpopulations assessed with the FST method was higher at the level of the Croatian population (0.005) than at the level of Southeastern Europe (0.002). The island of Vis showed the most pronounced separation in the Croatian population, and Albanians from Kosovo in the population of Southeast Europe, followed by Croatia, Bosnia and Herzegovina, and Hungary. CONCLUSION: The higher structure of Croatian subpopulations in relation to Southeastern Europe suggest a certain degree of genetic isolation, most likely due to the influence of endogamy within rural island populations.
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Impressões Digitais de DNA , Genética Populacional , Bósnia e Herzegóvina , Croácia , Europa (Continente) , Frequência do Gene , Humanos , Repetições de MicrossatélitesRESUMO
AIM: To investigate the influence of specific intrapopulation genetic structures on interpopulation relationships. Special focus was the influence of island population isolation on the substructuring of the Croatian population, and the influence of regional population groups on the substructuring of Southeast European populations. METHODS: Autosomal short tandem repeat (STR) loci were analyzed by using four forensic parameters: matching probability (PM), power of discrimination (PD), power of exclusion (PE), and polymorphic information content (PIC) on a sample of 2877 unrelated participants of both sexes. A sample set comprising 590 participants was analyzed for the first time, and 2287 participants were included from previous studies. The analysis was performed with PowerStats v. 1.2. RESULTS: The analysis of forensic parameters for all nine loci in the Croatian subpopulations showed the largest deviations in the populations of the islands of Korcula and Hvar. The smallest deviations were found in the mainland population. As for Southeast European populations, the largest deviations were found in the population of North Macedonia, followed by Romania, Albanians from Kosovo, and Montenegro, while the smallest deviations were found in the population of Hungary. CONCLUSION: The comparison of forensic parameters between different subpopulations of Croatia and Southeast Europe indicates that the isolation of individual Croatian subpopulations and rare alleles in their gene pool affect the values of forensic parameters. Specific features of (sub)populations should be taken into account for appropriate sampling of the total population when creating a DNA database of STR markers.
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Genética Populacional , Polimorfismo Genético , Europa (Continente) , Feminino , Frequência do Gene , Humanos , Masculino , Repetições de Microssatélites/genéticaRESUMO
OBJECTIVES: 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). MATERIALS AND METHODS: A high-resolution phylogenetic and phylogeographic analysis of 66 biallelic (SNPs) and 17 microsatellite (STRs) markers of the Y chromosome was performed using 720 Croatian samples. The obtained results were placed in a wider European context by comparison with â¼4450 samples from a number of other European populations. RESULTS: A high diversity of haplogroups was observed in the overall Croatian sample, and all typical European Y chromosome haplogroups with corresponding clinal patterns were observed. Three distinct genetic signals were identifiable in the Croatian paternal gene pool - I2a1b-M423, R1a1a1b1a*-M558, and E1b1b1a1b1a-V13 haplogroups. DISCUSSION: The analyses of the dominant and autochthonous I2a1b-M423 lineage (>30%) suggest that SEE had a significant role in the Upper Paleolithic, the R1a1a1b1a*-M558 lineage (19%) represents a signal from present day Slavic populations of Central Europe in the Croatian population, and the phylogeography of the E1b1b1a1b1a-V13 clade (around 9%) implies cultural diffusion of agriculture into Europe via the Balkan Peninsula. Am. J. Hum. Biol., 2016. © 2016 Wiley Periodicals, Inc. Am. J. Hum. Biol. 28:837-845, 2016. © 2016Wiley Periodicals, Inc.
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Cromossomos Humanos Y/genética , Pool Gênico , Variação Genética , Filogenia , Croácia , Humanos , Ilhas , MasculinoRESUMO
Due to its turbulent demographic history, marked by extensive settlement and gene flow from diverse regions of Eurasia, Southeastern Europe (SEE) has consistently served as a genetic crossroads between East and West and a junction for the migrations that reshaped Europe's population. SEE, including modern Croatian territory, was a crucial passage from the Near East and even more distant regions and human populations in this region, as almost any other European population represents a remarkable genetic mixture. Modern humans have continuously occupied this region since the Upper Paleolithic era, and different (pre)historical events have left a distinctive genetic signature on the historical narrative of this region. Our views of its history have been mostly renewed in the last few decades by extraordinary data obtained from Y-chromosome studies. In recent times, the international research community, bringing together geneticists and archaeologists, has steadily released a growing number of ancient genomes from this region, shedding more light on its complex past population dynamics and shaping the genetic pool in Croatia and this part of Europe.
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Cromossomos Humanos Y , Genética Populacional , Humanos , Cromossomos Humanos Y/genética , Croácia , Genética Populacional/métodos , Pool Gênico , DNA Antigo/análise , Fluxo Gênico , Migração Humana , MasculinoRESUMO
Mitochondrial DNA (mtDNA) has been used for decades as a predominant tool in population genetics and as a valuable addition to forensic genetic research, owing to its unique maternal inheritance pattern that enables the tracing of individuals along the maternal lineage across numerous generations. The dynamic interplay between evolutionary forces, primarily genetic drift, bottlenecks, and the founder effect, can exert significant influence on genetic profiles. Consequently, the Adriatic islands have accumulated a subset of lineages that exhibits remarkable absence or rarity within other European populations. This distinctive genetic composition underscores the islands' potential as a significant resource in phylogenetic research, with implications reaching beyond regional boundaries to contribute to a global understanding. In the initial attempt to expand the mitochondrial forensic database of the Croatian population with haplotypes from small isolated communities, we sequenced mitogenomes of rare haplogroups from different Croatian island and mainland populations using next-generation sequencing (NGS). In the next step and based on the obtained results, we refined the global phylogeny of haplogroup N1a, HV2, and X by analyzing rare haplotypes, which are absent from the current phylogenetic tree. The trees were based on 16 novel and 52 previously published samples, revealing completely novel branches in the X and HV2 haplogroups and a new European cluster in the ancestral N1a variant, previously believed to be an exclusively African-Asian haplogroup. The research emphasizes the importance of investigating geographically isolated populations and their unique characteristics within a global context.
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Genoma Mitocondrial , Humanos , Filogenia , Croácia , Genoma Mitocondrial/genética , Mitocôndrias/genética , DNA Mitocondrial/genéticaRESUMO
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.
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Polimorfismo de Nucleotídeo Único , Ácido Úrico/sangue , Croácia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , MasculinoRESUMO
Previous studies have confirmed the beneficial effect of a Mediterranean diet in mitigating health issues related to cardiovascular disease, diabetes and obesity. However, rapid changes in the traditional way of life and the "westernization" of the diet in Mediterranean populations, especially in younger generations, has led to progressive abandonment of healthy dietary patterns. In order to investigate the generation shift in dietary patterns and lifestyle habits in the Mediterranean part of Croatia, we compared two cohorts of 610 women (266 pregnant and 344 non-pregnant) from the same region, but from different age groups. The MDSS score was derived from food frequency questionnaires. The results showed that the young, reproductively active generation (pregnant women) in Dalmatia, Croatia, although having a higher education and socioeconomic status, exhibits a more adverse eating behaviour (lower adherence to the Mediterranean diet) and lifestyle (excessive smoking in pregnancy) than the older population from the same region. Lower MDSS scores across aggregated age groups in both cohorts showed significant association with higher blood lipid levels and higher smoking frequency. In conclusion, Mediterranean diet adherence is associated with biological markers (age, lipid profile) and lifestyle (smoking) in our study, with a more adverse trend observed in the younger generation.
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Dieta Mediterrânea/estatística & dados numéricos , Nível de Saúde , Estilo de Vida , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Croácia/epidemiologia , Exercício Físico , Comportamento Alimentar , Feminino , Humanos , Lipídeos/sangue , Pessoa de Meia-Idade , Gravidez , Fumar/epidemiologia , Classe Social , Inquéritos e Questionários , Adulto JovemRESUMO
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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Dieta Mediterrânea , Estilo de Vida , Fenômenos Fisiológicos da Nutrição Materna , Adulto , Índice de Massa Corporal , Estudos de Coortes , Croácia , Dieta Saudável , Exercício Físico , Feminino , Seguimentos , Comportamentos Relacionados com a Saúde , Humanos , Avaliação Nutricional , Cooperação do Paciente , Gravidez , Gestantes , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Diversity of mitochondrial DNA (mtDNA) lineages of the Island of Cres was determined by high-resolution phylogenetic analysis on a sample of 119 adult unrelated individuals from eight settlements. The composition of mtDNA pool of this Island population is in contrast with other Croatian and European populations. The analysis revealed the highest frequency of haplogroup U (29.4%) with the predominance of one single lineage of subhaplogroup U2e (20.2%). Haplogroup H is the second most prevalent one with only 27.7%. Other very interesting features of contemporary Island population are extremely low frequency of haplogroup J (only 0.84%), and much higher frequency of haplogroup W (12.6%) comparing to other Croatian and European populations. Especially interesting finding is a strikingly higher frequency of haplogroup N1a (9.24%) presented with African/south Asian branch almost absent in Europeans, while its European sister-branch, proved to be highly prevalent among Neolithic farmers, is present in contemporary Europeans with only 0.2%. Haplotype analysis revealed that only five mtDNA lineages account for almost 50% of maternal genetic heritage of this island and they present supposed founder lineages. All presented findings confirm that genetic drift, especially founder effect, has played significant role in shaping genetic composition of the isolated population of the Island of Cres. Due to presented data contemporary population of Cres Island can be considered as genetic "outlier" among Croatian populations.
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DNA Mitocondrial/genética , Efeito Fundador , Variação Genética , Filogenia , Adulto , Croácia , Haplótipos/genética , Humanos , População Branca/etnologia , População Branca/genéticaRESUMO
OBJECTIVE: 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). DESIGN AND METHODS: Cross-sectional data were collected on 1,300 individuals from an eastern Adriatic Croatian island, including 14 anthropometric and biochemical traits, and diagnoses of type 2 diabetes, coronary heart disease, gout, kidney disease, and stroke. MetS was defined based on Adult Treatment Panel III criteria. Forty widely replicated GWAS variants were genotyped. Correlated quantitative traits were reduced through factor analysis; relationships between factors, genetic variants, MetS, and metabolic diseases were determined through SEM. RESULTS: MetS was associated with obesity (P < 0.0001), dyslipidemia (P < 0.0001), glycated hemoglobin (HbA1c; P = 0.0013), hypertension (P < 0.0001), and hyperuricemia (P < 0.0001). Of metabolic diseases, MetS was associated with gout (P = 0.024), coronary heart disease was associated with HbA1c (P < 0.0001), and type 2 diabetes was associated with HbA1c (P < 0.0001) and obesity (P = 0.008). Eleven GWAS variants predicted metabolic variables, MetS, and metabolic diseases. Notably, rs7100623 in HHEX/IDE was associated with HbA1c (ß = 0.03; P < 0.0001) and type 2 diabetes (ß = 0.326; P = 0.0002), underscoring substantial impact on glucose control. CONCLUSIONS: Although MetS was associated with obesity, dyslipidemia, glucose control, hypertension, and hyperuricemia, limited ability of MetS to indicate metabolic disease risk is suggested.
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Estudo de Associação Genômica Ampla , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Comorbidade , Estudos Transversais , Dislipidemias/epidemiologia , Feminino , Genótipo , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertensão/epidemiologia , Hiperuricemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/epidemiologia , Fenótipo , Análise de Regressão , Fatores de Risco , Adulto JovemRESUMO
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.
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Alelos , Estatura/genética , Heterogeneidade Genética , Variação Genética , Análise de Variância , Análise por Conglomerados , HumanosRESUMO
Twenty-two single-nucleotide polymorphisms (SNPs) in 10 gene regions previously identified in obesity and type 2 diabetes (T2D) genome-wide association studies (GWAS) were evaluated for association with metabolic traits in a sample from an island population of European descent. We performed a population-based study using 18 anthropometric and biochemical traits considered as continuous variables in a sample of 843 unrelated subjects (360 men and 483 women) aged 18-80 years old from the island of Hvar on the eastern Adriatic coast of Croatia. All eight GWAS SNPs in FTO were significantly associated with weight, body mass index, waist circumference and hip circumference; 20 of the 32 nominal P-values remained significant after permutation testing for multiple corrections. The strongest associations were found between the two TCF7L2 GWAS SNPs with fasting plasma glucose and HbA1c levels, all four P-values remained significant after permutation tests. Nominally significant associations were found between several SNPs and other metabolic traits; however, the significance did not hold after permutation tests. Although the sample size was modest, our study strongly replicated the association of FTO variants with obesity-related measures and TCF7L2 variants with T2D-related traits. The estimated effect sizes of these variants were larger or comparable to published studies. This is likely attributable to the homogenous genetic background of the relatively isolated study population.
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Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Adulto , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Índice de Massa Corporal , Peso Corporal , Croácia , Feminino , Predisposição Genética para Doença , Genótipo , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Grupos Populacionais , Circunferência da CinturaRESUMO
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 2â¼10% 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.