showing 15 related works from this author
Heritability and genome-wide association analyses of sleep duration in children: The EAGLE Consortium.
2016
STUDY OBJECTIVES: Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits.METHODS: We performed a population-based molecular genetic study, using data form the EArly Genetics and Life course Epidemiology (EAGLE) Cons…
Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
2019
AbstractBirth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genoty…
Orexin and sleep quality in anorexia nervosa: Clinical relevance and influence on treatment outcome
2015
Background and aims Orexins/hypocretins are orexigenic peptides implicated in the regulation of feeding behavior and the sleep/wake cycle. Little is known about the functioning of these peptides in anorexia nervosa (AN). The aims of the current study were to evaluate the extent to which orexin-A might be linked to sleep and treatment outcome in AN. Method Fasting plasma orexin-A concentrations were measured in 48 females with AN at the start of a day hospital treatment and in 98 normal-eater/healthy-weight controls. The Pittsburgh Sleep Quality Index was administered at the beginning of the treatment as a measure of sleep quality. Other psychopathological variables were evaluated with the S…
Detailed analysis of inversions predicted between two human genomes: errors, real polymorphisms, and their origin and population distribution.
2016
The growing catalogue of structural variants in humans often overlooks inversions as one of the most difficult types of variation to study, even though they affect phenotypic traits in diverse organisms. Here, we have analysed in detail 90 inversions predicted from the comparison of two independently assembled human genomes: the reference genome (NCBI36/HG18) and HuRef. Surprisingly, we found that two thirds of these predictions (62) represent errors either in assembly comparison or in one of the assemblies, including 27 misassembled regions in HG18. Next, we validated 22 of the remaining 28 potential polymorphic inversions using different PCR techniques and characterized their breakpoints …
KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron
2012
Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins tha…
Circulating Betatrophin Levels Are Increased in Anorexia and Decreased in Morbidly Obese Women.
2015
Betatrophin is produced primarily by liver and adipose tissue and has been recently reported as a novel hormone promoting β-cell proliferation and β-cell mass and improving glucose tolerance.Because it is markedly regulated by nutritional status, we hypothesized that circulating betatrophin levels might be affected by pathophysiological conditions altering body weight.We analyzed circulating betatrophin levels in 149 female patients, including 99 with extreme body mass index (30 anorexia nervosa, 24 obese, 45 morbid obese, and 50 healthy eating/weight controls).Serum betatrophin levels and its correlations with different anthropometric and biochemical parameters were measured.Plasma betatro…
Genetic variations of the bitter taste receptor TAS2R38 are associated with obesity and impact on single immune traits
2015
Scope: Changes in genetic variations affecting the taste receptor, type 2, member 38 (TAS2R38) may identify the interacting mechanism leading to obesity and potential associations with proteins partaking in innate immunity, such as surfactant protein D (SPD) and mannan-binding lectin (MBL). Methods and results: We evaluated haplotypes of the bitter-taste receptor TAS2R38 in an identification sample of 210 women in different weight conditions, including anorexia nervosa and obesity. The association with SPD and MBL was tested in an independent sample picturing general population (n = 534). The relationship with obesity was validated in an extended final sample of 1319 participants. In the sa…
A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways
2016
More than a million childhood diarrhoeal episodes occur worldwide each year, and in developed countries a considerable part of them are caused by viral infections. In this study, we aimed to search for genetic variants associated with diarrhoeal disease in young children by meta-analyzing genome-wide association studies, and to elucidate plausible biological mechanisms. The study was conducted in the context of the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Data about diarrhoeal disease in two time windows (around 1 year of age and around 2 years of age) was obtained via parental questionnaires, doctor interviews or medical records. Standard quality control and statistic…
Influence of fetal glutathione S-transferase copy number variants on adverse reproductive outcomes
2012
A nested case-control association study was designed to investigate the influence of maternal and fetal copy number variants (CNVs) on reproductive outcomes. Genotypes of ten CNVs encompassing GST and CYP genes were assessed. Significant associations were only found for child CNV genotypes. In particular, the child GSTM1 insertion allele was associated with prematurity protection (odds ratio, 95% CI: 0.67, 0.51-0.89; P < 0.01), whereas the child GSTT2B insertion allele was associated with an increased risk of being small for gestational age (odds ratio, 95% CI: 1.33, 1.07-1.67; P = 0.01). The study highlights the role of the fetal genome in prenatal development and also the need to analyse …
Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
2020
AbstractEating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], …
Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women.
2009
The post-partum period is a time of extreme vulnerability for a whole spectrum of psychiatric disorders. Delivery may be considered an important risk factor in genetically susceptible women. Five hundred and eight SNPs in 44 genes at candidate pathways putatively related to mood changes after delivery were genotyped in a multicenter cohort of 1804 women from Spain. Participants completed two scales at 2-3 days, 8 weeks, and 32 weeks post-partum, the Edinburgh Post-partum Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Those women who scored 9 or more on EPDS were evaluated for major depression using the Diagnostic Interview for Genetics Studies (DIGS) adapt…
Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy
2016
BACKGROUND: We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight. METHODS: DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We ex…
Prenatal exposure to mixtures of xenoestrogens and genome-wide DNA methylation in human placenta
2015
BACKGROUND: In utero exposure to xenostrogens may modify the epigenome. We explored the association of prenatal exposure to mixtures of xenoestrogens and genome-wide placental DNA methylation. MATERIALS & METHODS: Sex-specific associations between methylation changes in placental DNA by doubling the concentration of TEXB-alpha exposure were evaluated by robust multiple linear regression. Two CpG sites were selected for validation and replication in additional male born placentas. RESULTS: No significant associations were found, although the top significant CpGs in boys were located in the LRPAP1, HAGH, PPARGC1B, KCNQ1 and KCNQ1DN genes, previously associated to birth weight, Type 2 diabetes…
Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta
2014
BACKGROUND: Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. OBJECTIVES: In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. METHODS: The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear …
Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary …
2023
Funder: British Lung Foundation (BLF); doi: https://doi.org/10.13039/501100000351