[Show abstract][Hide abstract] ABSTRACT: Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.Molecular Psychiatry advance online publication, 2 December 2014; doi:10.1038/mp.2014.133.
[Show abstract][Hide abstract] ABSTRACT: To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.
[Show abstract][Hide abstract] ABSTRACT: Background. Several psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study. Method. The present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter-Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test - immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms. Results. Compared with no-grief participants, participants with complicated grief had lower scores for the Letter-Digit Substitution Test [Z-score -0.16 v. 0.04, 95% confidence interval (CI) -0.36 to -0.04, p = 0.01] and Word Fluency Task (Z-score -0.15 v. 0.03, 95% CI -0.35 to -0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI -37.6 to -0.10, p = 0.04). Conclusions. Participants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.
[Show abstract][Hide abstract] ABSTRACT: Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.Molecular Psychiatry advance online publication, 7 October 2014; doi:10.1038/mp.2014.107.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood.
METHODS AND RESULTS: To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501; relative risk [RR]=1.18; 95% confidence interval [CI], 1.13-1.23; P=6.5×10(-16)), GJA1 (rs13216675; RR=1.10; 95% CI, 1.06-1.14; P=2.2×10(-8)), TBX5 (rs10507248; RR=1.12; 95% CI, 1.08-1.16; P=5.7×10(-11)), and CAND2 (rs4642101; RR=1.10; 95% CI, 1.06-1.14; P=9.8×10(-9)). In Japanese, novel loci were identified near NEURL (rs6584555; RR=1.32; 95% CI, 1.26-1.39; P=2.0×10(-25)) and CUX2 (rs6490029; RR=1.12; 95% CI, 1.08-1.16; P=3.9×10(-9)). The top single-nucleotide polymorphisms or their proxies were identified as cis-eQTLs for the genes CAND2 (P=2.6×10(-19)), GJA1 (P=2.66×10(-6)), and TBX5 (P=1.36×10(-5)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively).
CONCLUSIONS: We have identified 5 novel loci for AF. Our results expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation.
[Show abstract][Hide abstract] ABSTRACT: Background
Excessive gestational weight gain seems to be associated with offspring cardio-metabolic risk factors. Little is known about critical periods of gestational weight gain. We examined the associations of maternal weight gain in different periods of pregnancy with childhood cardio-metabolic risk factors.Methods
In a population-based prospective cohort study from early-pregnancy onwards among 5,908 mothers and their children, we obtained maternal prepregnancy weight and weight in early-, mid- and late-pregnancy. At the age of 6 years (median: 72.6 months; 95% range: 67.9, 95.8), we measured childhood BMI, total body and abdominal fat distribution, blood pressure and blood levels of lipids, insulin and c-peptide.ResultsOverall, the associations of maternal prepregnancy weight with childhood outcomes were stronger than the associations of maternal gestational weight gain. Independent from maternal prepregnancy weight and weight gain in other periods, higher weight gain in early-pregnancy was associated with higher childhood BMI, total fat mass, android/gynoid fat mass ratio, abdominal subcutaneous fat mass and systolic blood pressure (P-values<0.05). Independent associations of maternal weight gain in early-pregnancy with childhood abdominal preperitoneal fat mass, insulin and c-peptide were of borderline significance. Higher weight gain in mid-pregnancy was independently associated with higher childhood BMI, total and abdominal subcutaneous fat mass and systolic blood pressure (P-values<0.05). The associations for childhood cardio-metabolic outcomes attenuated after adjustment for childhood BMI. Weight gain in late-pregnancy was not associated with childhood outcomes. Higher weight gain in early-, but not in mid- or late-pregnancy, was associated with increased risks of childhood overweight and clustering of cardio-metabolic risk factors (Odds Ratio (OR) 1.19 (95% Confidence Interval (CI): 1.10, 1.29) and OR 1.20 (95% CI: 1.07, 1.35) per standard deviation increase in early-gestational weight gain, respectively).Conclusions
Higher weight gain in early-pregnancy is associated with an adverse cardio-metabolic profile in offspring. This association is largely mediated by childhood adiposity.International Journal of Obesity accepted article preview online, 07 October 2014. doi:10.1038/ijo.2014.175.
International journal of obesity (2005) 10/2014; · 5.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
[Show abstract][Hide abstract] ABSTRACT: FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake, and body mass index (BMI) are complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154,439 whites, 5,776 African Americans, and 17,115 Asians) from 40 studies to examine: 1) the association between the FTO-rs9939609 variant (or a proxy SNP) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in whites (effect per allele =0.34 [0.31, 0.37] kg/m(2), P=1.9×10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P=3.6×10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele =0.08[0.06, 0.10]%, P=2.4×10(-16)), and relative weak associations with lower total energy intake (-6.4[-10.1, -2.6] kcal/day, P=0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02]%, P=0.004). The associations with protein (P=7.5×10(-9)) and total energy (P =0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate, or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
Human Molecular Genetics 08/2014; · 7.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
[Show abstract][Hide abstract] ABSTRACT: Proprotein convertase subtilisin/kexin-type 1 (PCSK1) activates precursors pro-opiomelanocortin (POMC), proinsulin and prorenin. We investigated if common variants in the PCSK1 gene influence blood pressure and risk of hypertension. Additionally, we investigated the risk of obesity and type 2 diabetes (T2D). In the Rotterdam Study (RS1), a prospective, population-based cohort (n=5974), four single-nucleotide polymorphisms (rs10515237, rs6232, rs436321 and rs3792747) in PCSK1 were studied. Linear and Cox regression models served to analyze associations between variants and end points. Replication was performed in the Rotterdam Study Plus1 (RSPlus1, n=1895). Rs436321 was significantly associated with systolic and diastolic blood pressure and risk of hypertension (odds ratio (OR): 1.1-1.3; P<0.05 in both populations). Rs6232 was associated with body mass index (BMI) (P=0.007 and P=0.04 in RS1 and RSPlus1, respectively). In RSPlus1, heterozygotes for rs6232 had 1.5 times higher risk of obesity (OR: 1.46; 95% confidence interval: 1.04-2.03; P=0.03). We did not find significant associations of PCSK1 with fasting insulin levels and T2D. We found an association of genetic variation in the PCSK1 gene with blood pressure and hypertension. Furthermore, we replicated the association of PCSK1 with BMI and obesity. No relationship was found between PCSK1 variants and fasting insulin levels and T2D. Our findings suggest that genetic variation in PCSK1 may contribute to, at least, some of these interrelated disorders.Journal of Human Hypertension advance online publication, 17 July 2014; doi:10.1038/jhh.2014.59.
Journal of Human Hypertension 07/2014; · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While many neuroimaging studies have investigated the neurobiological basis of attention deficit hyperactivity disorder (ADHD), few have studied the neurobiology of attention problems in the general population. The ability to pay attention falls along a continuum within the population, with children with ADHD at one extreme of the spectrum and, therefore, a dimensional perspective of evaluating attention problems has an added value to the existing literature. Our goal was to investigate the relationship between cortical thickness and inattention and hyperactivity symptoms in a large population of young children.
Psychological Medicine 07/2014; · 5.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background ("Dutch hypothesis"). We investigated whether asthma and COPD have common underlying genetic factors, performing genome-wide association studies for both asthma and COPD and combining the results in meta-analyses. Three loci showed potential involvement in both diseases: chr2p24.3, chr5q23.1 and chr13q14.2, containing DDX1, COMMD10 (both participating in the nuclear factor (NF) kappabeta pathway) and GNG5P5, respectively. Single nucleotide polymorphisms (SNPs) rs9534578 in GNG5P5 reached genome-wide significance after first replication phase (p = 9.96x10-9). The second replication phase, in seven independent cohorts, provided no significant replication. Expression quantitative trait loci (eQTL) analysis in blood cells and lung tissue on the top 20 associated SNPs identified two SNPs in COMMD10 that influenced gene expression. Inflammatory processes differ in asthma and COPD and are mediated by NF-kappabeta, which could be driven by the same underlying genes, COMMD10 and DDX1. None of the SNPs reached genome-wide significance. Our eQTL studies support a functional role for two COMMD10 SNPs, since they influence gene expression in both blood cells and lung tissue. Our findings suggest that there is either no common genetic component in asthma and COPD or, alternatively, different environmental factors, e.g. lifestyle and occupation in different countries and continents, which may have obscured the genetic common contribution.
European Respiratory Journal 07/2014; · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 x 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 x 10-7). In addition, meta-analysis using the five cohorts with >/=3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 x 10-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.
[Show abstract][Hide abstract] ABSTRACT: Background: Alzheimer’s disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer’s Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer’s cases and 48,466 controls.
Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p=1.461026) and 14 (IGHV1-67 p=7.961028) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer’s disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer’s disease
PLoS ONE 06/2014; 9(6):e94661. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsTo investigate whether polymorphisms in SLC6A20 are associated with susceptibility to Type 2 diabetes.Methods
In the Rotterdam Study, a prospective, population-based cohort (n=5974), 22 tagging polymorphisms with minor allele frequencies>0.05 across SLC6A20 were studied. Replication studies were performed in an independent Dutch case–control study (DiaGene-Rotterdam Study 2 n=3133), and in a Chinese Han case–control population (n=2279). A meta-analysis of the results was performed.ResultsIn the Rotterdam study, the minor alleles of rs13062383, rs10461016 and rs2286489 increased the risk of Type 2 diabetes (hazard ratio 1.37, 95% CI 1.15–1.63, hazard ratio 1.30 95% CI 1.09–1.54 and hazard ratio 1.20, 95% CI 1.07–1.35, respectively). In the DiaGene/Rotterdam Study 2, the A allele of rs13062383 increased the risk of Type 2 diabetes (odds ratio 1.45, 95% CI 1.19–1.76). In the Chinese Han study, the rs13062383 A allele also increased the risk of Type 2 diabetes (odds ratio 1.21, 95% CI 1.03–1.42). Meta-analysis showed a highly significant association of rs13062383 with Type 2 diabetes (odds ratio 1.35, 95% CI 1.21–1.47; P=3.3×10-8).Conclusions
In conclusion, rs13062383 in SLC6A20 increased the susceptibility to Type 2 diabetes in populations with different genetic backgroundsThis article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis with its consequences, i.e., fractures, is major health problem in ageing societies. As osteoporosis is a prevalent disorder, understanding its etiological factors is very important. We recently identified novel pathogenic variants in PLS3 (encoding Plastin 3 (PLS3), a filamentous-actin bundling protein) as a cause of X-linked osteoporosis and osteoporotic fractures in five Dutch families (van Dijk et al. NEJM 2013:369(16):1529-36). These loss-of-function variants cause decreased bone mineral density and increased risk of fracture in hemizygous young men whereas the clinical picture in heterozygous women ranged from asymptomatic to early-onset osteoporosis. It was highly unexpected that mutations in this gene would cause osteoporosis and fractures as it had never been described as a candidate gene for osteoporosis nor was it known to play a role in bone formation. However, results of in vivo analyses in zebrafish strongly supported a role for PLS3 as a bone regulatory protein. Furthermore, a rare variant (rs140121121) in PLS3 was found to be associated with a twofold increased fracture risk in elderly female carriers in the normal population indicating genetic variation in PLS3 as a novel etiological factor involved in common, multifactorial osteoporosis. However, the exact mechanism by which PLS3 mutations cause osteoporosis and fractures is unknown and currently subject of further investigations. Unravelling this new bone regulatory pathway is of great importance for understanding the aetiology of osteoporosis, increasing also the possibilities for prevention, diagnosis and treatment aimed at bone formation.
EUROPEAN HUMAN GENETICS CONFERENCE 2014, Milan, Italy; 05/2014
[Show abstract][Hide abstract] ABSTRACT: Parents’ restriction of food intake has consistently been associated with a higher body mass index (BMI) in children. It is assumed that parental restriction weakens children’s self-regulation, but restriction may also be a parent’s response to child overweight. With few exceptions, studies have not examined this possibility. In longitudinal analyses, we aimed to identify directionality in the restrictive feeding–BMI relationship among preschoolers. BMI was measured among 3478 children in the population-based Generation R Study. Restriction (Child Feeding Questionnaire) was self-reported by parents. Bi-directionality was examined in a path analysis with Restriction and BMI expressed in standard deviation (SD) scores. Path analysis jointly estimating Restriction–BMI associations in both directions and accounting for continuity in BMI over time indicated that a higher BMI at age 2 years was associated with more restriction at age 4 years, which in turn was positively related with child BMI two years later. However, associations were modest, e.g. for each SD increase in Restriction, child BMIz increased by 0.07 (95% CI: 0.04, 0.10). The relation from BMI to parenting was stronger than reverse (Wald test for comparison: p-value = 0.03). Our results imply a bi-directional relation between restrictive feeding and child BMI. This suggests that, in contrast to school-age children, among preschoolers a cyclical relationship may appear: the main direction of effect was parents responding to high child weight by restriction of food intake, while excessive restriction may also have a small counterproductive effect resulting in overeating and adiposity.
[Show abstract][Hide abstract] ABSTRACT: Background:Breastfeeding duration is associated with the risks of cardio-metabolic diseases in adulthood. We examined the associations of infant feeding patterns with metabolic outcomes in children and whether any association was explained by family-based socio-demographic, maternal lifestyle-related or childhood factors.Subjects/methods:We performed a population-based prospective cohort study in 3417 children to examine the associations of breastfeeding duration and exclusivity and age at introduction of solid foods with blood levels of lipids, insulin and C-peptide and risk of clustering of cardio-metabolic risk factors at the median age of 6.0 years (90% range 5.7-6.8).Results:We observed that, in the models only adjusted for child's age and sex, ever breastfeeding was not associated with childhood blood levels of lipids but was associated with higher insulin and C-peptide concentrations (P-value<0.05). Breastfeeding duration and exclusivity were not consistently associated with metabolic outcomes. Early introduction of solid foods was associated with higher levels of total cholesterol (P-value<0.05) but not with high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides and insulin levels. Shorter breastfeeding duration and exclusive breastfeeding were associated with increased risks of clustering of cardio-metabolic risk factors. After additional adjustment for family, maternal and childhood factors, none of these associations remained significant.Conclusions:In conclusion, we found no consistent associations of infant feeding patterns with metabolic outcomes at school age, after taking into account family-based socio-demographic, maternal lifestyle-related or childhood factors. Whether infant diet composition influences metabolic outcomes in later life should be further studied.European Journal of Clinical Nutrition advance online publication, 30 April 2014; doi:10.1038/ejcn.2014.81.
European journal of clinical nutrition 04/2014; · 3.07 Impact Factor