George Dedoussis

Harokopio University | HUA · Department of Nutrition and Dietetics

The present study sought to retrospectively investigate the dietary habits of two adolescent, European populations from the cross-sectional Greek TEENAGE Study and French STANISLAS Family Study. We aimed to explore the relation between the populations’ dietary patterns and blood pressure, glycemic and lipidemic profile. Dietary patterns were extrac...

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the di...

Diet is a modifiable key factor targeted in prevention and management of nonalcoholic fatty liver disease (NAFLD). The aim was to study the effect of Mediterranean Diet (MedDiet) on clinical, biochemical, and inflammatory profile in NAFLD patients with simple steatosis. Potential associations of signal transducer and activator of transcription 3 (S...

PurposeNon-alcoholic fatty liver disease (NAFLD) is a complex disease, resulting from a variety of genetic and environmental factors. The aim of this case–control study was to evaluate the effect of selected genetic polymorphisms, nutrition aspects and their interaction on the risk of NAFLD. Methods The sample consisted of 134 patients with NAFLD a...

Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome. Its global prevalence is estimated between 25 and 45%, occurring mainly in overweight individuals with unhealthy dietary habits and low levels of physical activity. Many studies have investigated the association of trace elements with liver di...

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide...

Vitamin D deficiency and quantitative ultrasound measurements are associated with bone fragility. We assessed these parameters and their correlates. 87.7% of the population has vitamin D inadequacy and this correlated with lifestyle factors. These results contribute to epidemiological data needed for population guidelines for bone health. Purpose...

Aim: To investigate the association between GCKR gene and nutritional treatment in NAFLD-related biomarkers. Methods: This was an open-label and single-arm clinical trial in 44 overweight or obese adults with NAFLD receiving nutritional counseling for 6 months. Nutritional data, MedDietScore, clinical, biochemical, inflammatory and oxidative str...

Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment

Background: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution...

BACKGROUND:Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. OBJECTIVE:To identify common genetic variants that influence fish and dietary eicosapentaeno...

Purpose: Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual....

Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with glucose levels. We tested the hypothesis here whether the cumulative effect of glucose raising SNPs, assessed via a score, is associated with glucose levels. A total of 1,434 participants of Greek descent from the THISEAS study and...

Estimated power of the analyses for alpha 0.05. Lines represent the different power values to detect the effect in the model for the association of the weighted genetic risk score (GRS) with the trait. Calculations were performed using Quanto v1.2.4. (TIF)

Scatterplot of the positive correlation between the genetic risk scores and glucose levels (mmol/L) in the THISEAS study. A. unweighted genetic risk score (GRS) and glucose levels (mmol/L) and B. weighted genetic risk score (wGRS) and glucose levels (mmol/L). (TIF)

Study-specific descriptive statistics of the cohorts. Age, weighted Genetic Risk Score (wGRS), unweighted Genetic Risk Score (GRS) and Glucose (mmol/L). Data are presented as means ± SD for the total sample. (XLSX)

THISEAS association summary statistics for glucose levels associated loci with glucose levels. Effect sizes (beta) and SE are given for Glucose (mmol/L), Imputation quality: info > 0.97. Chr = chromosome, bp = base pairs, EAF = effect allele frequency, SE = standard error. Allelic test p, beta and SE are shown for each single SNP. Effect sizes (bet...

Associationsa analyses of the Genetic Risk Scores with glucose levels. aAdjusted for age and sex. bBeta coefficient and standard error for the estimated difference in glucose (mmol/L) values per 1-unit increase in the genetic risk scores (GRS and wGRS respectively -A and B-). bN indicates the sample size. (XLSX)

THISEAS association summary statistics for glucose levels associated loci with glucose levels. Effect sizes (beta) and SE are given for Glucose (mmol/L), Imputation quality: info > 0.97. Chr = chromosome, bp = base pairs, EAF = effect allele frequency, SE = standard error. Allelic test p, beta and SE are shown for each single SNP. Effect sizes (bet...

GOMAP association summary statistics for glucose levels associated loci with glucose levels. Effect sizes (beta) and SE are given for Glucose (mmol/L), Imputation quality: info > 0.97. Chr = chromosome, bp = base pairs, EAF = effect allele frequency, SE = standard error. Allelic test p, beta and SE are shown for each single SNP. Effect sizes (beta)...

GOMAP association summary statistics for glucose levels associated loci with glucose levels. Effect sizes (beta) and SE are given for Glucose (mmol/L), Imputation quality: info > 0.97. Chr = chromosome, bp = base pairs, EAF = effect allele frequency, SE = standard error. Allelic test p, beta and SE are shown for each single SNP. Effect sizes (beta)...

Meta-analysis association results for glucose levels associated loci with glucose levels. Effect sizes (β) and se are given for Glucose (mmol/L). Allelic test p, be and se are shown for each single SNP. Effect sizes (β) are reported for the effect allele. Adjustments: age and sex. An inverse variance weighted meta-analysis was performed. (XLSX)

Meta-analysis association results for glucose levels associated loci with glucose levels. Effect sizes (β) and se are given for Glucose (mmol/L). Allelic test p, be and se are shown for each single SNP. Effect sizes (β) are reported for the effect allele. Adjustments: age, sex and BMI. An inverse variance weighted meta-analysis was performed. (XLSX...

Associationsa analyses of the Genetic Risk Scores with glucose levels. aAdjusted for age, sex and BMI. bBeta coefficient and standard error for the estimated difference in glucose (mmol/L) values per 1-unit increase in the genetic risk scores (GRS and wGRS respectively -A and B-). bN indicates the sample size. (XLSX)

Scatterplot of the positive correlation between the genetic risk scores and glucose levels (mmol/L) in the GOMAP study. A. unweighted genetic risk score (GRS) and glucose levels (mmol/L) and B. weighted genetic risk score (wGRS) and glucose levels (mmol/L). (TIF)

Meta-analysis association results for glucose levels associated loci with glucose levels (mmol/L). Adjusted for age and sex, x-axis: Gene name, y-axis: -logPvalue. (TIF)

BACKGROUND: Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evide...

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine population...

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10(-8)) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the val...

The genetic features of isolated populations can boost power in complex-trait association studies, and an in-depth understanding of how their genetic variation has been shaped by their demographic history can help leverage these advantageous characteristics. Here, we perform a comprehensive investigation using 3,059 newly generated low-depth whole-...

Next-generation association studies can be empowered by sequence-based imputation and by studying founder populations. Here we report ∼9.5 million variants from whole-genome sequencing (WGS) of a Cretan-isolated population, and show enrichment of rare and low-frequency variants with predicted functional consequences. We use a WGS-based imputation a...

Supplementary Figures, Supplementary Tables, Supplementary Notes, Supplementary Methods and Supplementary References

Background: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with gen...

Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated...

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate fr...

Background Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. GWAS analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation.Aim To discover new genetic loci associated with heart rate from Exome Chip meta-analyses...

Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (P<5 × 10−8, METAL)...

Supplementary Figures, Supplementary Tables, Supplementary Note, and Supplementary References

Results of the enhancer enrichment analysis of MPB credible SNPs at the 63 genome-wide significant risk loci.

Shared genetic determinants between MPB and other human traits. MPB SNP - MPB lead SNP; GWAS SNP - reported GWAS SNP; CHR - chromosome, BP - base pair; EA - effect allele; OR - odds ratio; BETA - effect size; CI - confidence interval; MPB EA GWAS SNP - effect allele of GWAS SNP in MPB meta-analysis; LD - linkage desequilibrium; NR- not reported; +...

Functional description of genes that were identified as plausible candidate genes based on at least two of the following criteria: expression in human hair follicle (E), functional evidence from literature (F), vicinity to MPB lead SNP (N), evidence for cis-eQTL effect (Q), evidence from DEPICT analysis (D) (see Table 1). Chr. – Chromosome; PMID –...

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1–4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, ST...

Objective: We carried out de novo recruitment of a population-based cohort (MANOLIS study) and describe the specific population, which displays interesting characteristics in terms of diet and health in old age, through deep phenotyping. Design: Cross-sectional study where anthropometric, biochemical and clinical measurements were taken in addit...

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European...

The genetic architecture of human reproductive behavior—age at first birth (AFB) and number of children ever born (NEB)—has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood...

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derive...

Supplementary Figures 1-7, Supplementary Tables 1-5

Transferability of novel loci in other anthropometric GWAS

Phenotype summary statistics of all studies in 1st and 2nd stage analyses.

Association results for 189 GWAS-significant loci.

Genotyping description for all studies in 1st and 2nd stage analyses.

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derive...

Understanding human genetic diversity in Africa is important for interpreting the evolution of all humans, yet vast regions in Africa, such as Chad, remain genetically poorly investigated. Here, we use genotype data from 480 samples from Chad, the Near East, and southern Europe, as well as whole-genome sequencing from 19 of them, to show that many...

Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiome...

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environ...

In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female...

Aiming at investigating the potential effect of minimal dietary changes in NAFLD patients with non-significant fibrosis, 55 patients with NAFLD were enrolled in a randomized controlled clinical trial. Patients were assigned into two isocaloric dietary treatment groups for 24 weeks: (a) nutritional counseling (Control arm, N = 27), (b) nutritional c...

The Cd and Pb blood contents of healthy adult subjects who are non-occupationally exposed and living in the metropolitan area of Athens (Greece) have not been assessed thus far. Additionally, Greeks rank first among EU27 in terms of smoking habits. To fill the existing gap, we aimed to evaluate the predictors and propose reference values (RVs) of t...

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environ...

Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiome...

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for ind...

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were n...