A trans-ancestral meta-analysis of Genome-wide Association Studies reveals loci associated with childhood obesity

Although hundreds of GWAS-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity, and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of thirty studies consisting of up to 13,005 cases (≥95th percentile of BMI achieved 2-18 years old) and 15,599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1,888 cases and 4,689 controls from seven cohorts of European and North/South American ancestry. In addition to observing eighteen previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene: METTL15). The variant was nominally associated in only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than ten SNPs (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci

Maternal and fetal genetic contribution to gestational weight gain

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 to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (135G5) gene reached genome-wide significance (P =1.71 x 10(-8)) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG

Genetics of early-life head circumference and genetic correlations with neurological, psychiatric and cognitive outcomes

This is the final version. Available from BMC via the DOI in this record. Availability of data and materials GWAS summary data will be deposited at the EGG website (https://egg-consortium.org/) at publication. Individual study data are available from the corresponding author on reasonable request.Abstract Background: Head circumference is associated with intelligence and tracks from childhood into adulthood. Methods: We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age. Results: Seven loci reached genome-wide signifcance in the combined discovery and replication analysis of which three loci near ARFGEF2, MYCL1, and TOP1, were novel. We observed positive genetic correlations for early-life head circumference with adult intracranial volume, years of schooling, childhood and adult intelligence, but not with adult psychiatric, neurological, or personality-related phenotypes. Conclusions: The results of this study indicate that the biological processes underlying early-life head circumference overlap largely with those of adult head circumference. The associations of early-life head circumference with cognitive outcomes across the life course are partly explained by genetics.Wellcome TrustSimons FoundationWellcome TrustMRC & WTUniversity of Southern DenmarkMax Planck core societ

Genome-wide associations for birth weight and correlations with adult disease

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 disease1. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10−8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = −0.22, P = 5.5 × 10−13), T2D (Rg = −0.27, P = 1.1 × 10−6) and coronary artery disease (Rg = −0.30, P = 6.5 × 10−9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10−4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated

The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects

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 new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites

employed women: A controlled study

OBJECTIVE: The musculoskeletal pain is one of the leading health problems among employed women. The aim of our study was to examine musculoskeletal pain, depression and quality of life (QOL) among employed women and find out the differences with unemployed women

ambulation levels

OBJECTIVE: The aim of this study was to compare the musculoskeletal pain distribution, quality of life, and the hopelessness level in mothers with disabled children in different ambulation levels

functions and depression levels in breast cancer related lymph edema

[Purpose] Breast cancer-related upper extremity lymph edema is known to cause physical, functional and psychological impairments in women after modified radical mastectomy. The aim of this study was to investigate the effects of phase I Complex Decongestive Physiotherapy (CDP) on physical functions and depression levels in women with breast cancer-related upper extremity lymph edema. [Subjects and Methods] Fifty-eight subjects with breast cancer-related upper extremity lymph edema were the subjects of this study. The arm circumference, shoulder range of motion (ROM), muscle strength and depression levels of the subjects were assessed before and after phase I CDP treatment. [Results] After phase I CDP, there was a statistically significant reduction in circumference measurements at all levels of the affected arm. There was not any statistically significant difference in muscle strength after CDP. The shoulder ROM improved after treatment. There was a significant reduction in the Beck Depression Inventory score. A significant positive correlation was found between depression levels and circumference measurement. [Conclusion] Based on the results we suggest that by reducing limb volume, beside improving physical functions, phase I CDP can affect psychological status, especially depression which is very common in women with breast cancer-related upper extremity lymph edema

functions and depression levels in breast cancer related lymph edema

[Purpose] Breast cancer-related upper extremity lymph edema is known to cause physical, functional and psychological impairments in women after modified radical mastectomy. The aim of this study was to investigate the effects of phase I Complex Decongestive Physiotherapy (CDP) on physical functions and depression levels in women with breast cancer-related upper extremity lymph edema. [Subjects and Methods] Fifty-eight subjects with breast cancer-related upper extremity lymph edema were the subjects of this study. The arm circumference, shoulder range of motion (ROM), muscle strength and depression levels of the subjects were assessed before and after phase I CDP treatment. [Results] After phase I CDP, there was a statistically significant reduction in circumference measurements at all levels of the affected arm. There was not any statistically significant difference in muscle strength after CDP. The shoulder ROM improved after treatment. There was a significant reduction in the Beck Depression Inventory score. A significant positive correlation was found between depression levels and circumference measurement. [Conclusion] Based on the results we suggest that by reducing limb volume, beside improving physical functions, phase I CDP can affect psychological status, especially depression which is very common in women with breast cancer-related upper extremity lymph edema

The comparison of physical activity levels of university students with and without chronic nonspecific neck pain

Background and aims: Daily physical activity when performed sufficiently is widely known to have important health benefits. Reduced physical activity has been linked to several chronic health problems including chronic musculoskeletal compliants. Approximately 14-71% of adults experience neck pain at some points in their lifetime. The relationship between physical activity and neck pain is still controversial. The aim of this study was to compare physical activity levels of university students with and without chronic nonspecific neck pain (CNNP). Methods: The study was carried out amoung 118 university students at Pamukkale University in Denizli. The subjects were divided into two groups as having CNNP (group I, n=39) or not having CNNP (group II, n=79). The severity of neck pain was assessed by visual anolog scale (VAS) and neck disability index (NDI) was used for the assessment of disability resulting from CNNP. Physical activity levels of subjects were assessed the short form of International Physical Activity Questionnaire (IPAQ). Results: There was not any significant difference between two groups in terms of tptal physical activity levels (p>0,05). But a significant difference as found regarding vigorous-intensity activity levels which was lower with CNNP (p0,05, r=-0,11, r=-0,32). Conclusion: The results of study showed that the university students with CNNP had vigorous-intensity activity levels when compared with those who did not have CNNP which might be associated with depression and kinesiophobia as had been reported in previous studies