Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.
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SUBMITTER: Wahl S
PROVIDER: S-EPMC5570525 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
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Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.
Wahl Simone S Drong Alexander A Lehne Benjamin B Loh Marie M Scott William R WR Kunze Sonja S Tsai Pei-Chien PC Ried Janina S JS Zhang Weihua W Yang Youwen Y Tan Sili S Fiorito Giovanni G Franke Lude L Guarrera Simonetta S Kasela Silva S Kriebel Jennifer J Richmond Rebecca C RC Adamo Marco M Afzal Uzma U Ala-Korpela Mika M Albetti Benedetta B Ammerpohl Ole O Apperley Jane F JF Beekman Marian M Bertazzi Pier Alberto PA Black S Lucas SL Blancher Christine C Bonder Marc-Jan MJ Brosch Mario M Carstensen-Kirberg Maren M de Craen Anton J M AJ de Lusignan Simon S Dehghan Abbas A Elkalaawy Mohamed M Fischer Krista K Franco Oscar H OH Gaunt Tom R TR Hampe Jochen J Hashemi Majid M Isaacs Aaron A Jenkinson Andrew A Jha Sujeet S Kato Norihiro N Krogh Vittorio V Laffan Michael M Meisinger Christa C Meitinger Thomas T Mok Zuan Yu ZY Motta Valeria V Ng Hong Kiat HK Nikolakopoulou Zacharoula Z Nteliopoulos Georgios G Panico Salvatore S Pervjakova Natalia N Prokisch Holger H Rathmann Wolfgang W Roden Michael M Rota Federica F Rozario Michelle Ann MA Sandling Johanna K JK Schafmayer Clemens C Schramm Katharina K Siebert Reiner R Slagboom P Eline PE Soininen Pasi P Stolk Lisette L Strauch Konstantin K Tai E-Shyong ES Tarantini Letizia L Thorand Barbara B Tigchelaar Ettje F EF Tumino Rosario R Uitterlinden Andre G AG van Duijn Cornelia C van Meurs Joyce B J JB Vineis Paolo P Wickremasinghe Ananda Rajitha AR Wijmenga Cisca C Yang Tsun-Po TP Yuan Wei W Zhernakova Alexandra A Batterham Rachel L RL Smith George Davey GD Deloukas Panos P Heijmans Bastiaan T BT Herder Christian C Hofman Albert A Lindgren Cecilia M CM Milani Lili L van der Harst Pim P Peters Annette A Illig Thomas T Relton Caroline L CL Waldenberger Melanie M Järvelin Marjo-Riitta MR Bollati Valentina V Soong Richie R Spector Tim D TD Scott James J McCarthy Mark I MI Elliott Paul P Bell Jordana T JT Matullo Giuseppe G Gieger Christian C Kooner Jaspal S JS Grallert Harald H Chambers John C JC
Nature 20161221 7635
Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index ...[more]
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Project description:ObjectiveTo conduct an epigenome-wide analysis of DNA methylation and obesity traits.MethodsDNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled.ResultsEpigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n = 2,377) and the Atherosclerosis Risk in Communities study (n = 2,097), were found. Top findings were in CPT1A (meta-analysis P = 2.7 × 10(-43) for BMI and 9.9 × 10(-23) for WC), PHGDH (meta-analysis P = 2.0 × 10(-15) for BMI and 4.0 × 10(-9) for WC), CD38 (meta-analysis P = 6.3 × 10(-11) for BMI and 1.6 × 10(-12) for WC), and long intergenic non-coding RNA 00263 (meta-analysis P = 2.2 × 10(-16) for BMI and 8.9 × 10(-14) for WC), regions with biologically plausible relationships to adiposity.ConclusionsThis large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.
| S-EPMC4482015 | biostudies-literature
Project description:Genome wide DNA methylation profiling of MZ twins discordant and concordant for BMI. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,000 CpGs. Samples included 30 MZ twin pairs discordant for BMI and 10 pairs concordant for BMI.
2015-04-20 | GSE43975 | GEO
Project description:BackgroundDNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.MethodsWe examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.ResultsDNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10-7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10-4; adolescence Penrichment = 2.10 × 10-7).ConclusionsThere were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.
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Project description:This study investigated the association between pre-pregnancy body mass index (BMI) and adverse pregnancy outcomes among women participated in the National Free Preconception Health Examination Project in Guangdong Province, China, and explored these associations according to maternal age. Pre-pregnancy BMI was classified into underweight (BMI < 18.5 kg/m2), healthy weight (18.5-23.9 kg/m2), overweight (24.0-27.9 kg/m2), and obesity (≥ 28.0 kg/m2) according to Chinese criteria. Outcomes were preterm birth (PTB, delivery before 37 weeks of gestation), large for gestational age (LGA, birthweight above the 90th percentile for gestational age by infants' sex), small for gestational age (SGA, birthweight below the 10th percentile for gestational age by infants' sex), primary caesarean delivery, shoulder dystocia or birth injury, and stillbirth. Adjusted incidence risk ratios (aIRR) were calculated for underweight, overweight and obesity, respectively. Compared with healthy weight, underweight was associated with increased risk of PTB (aIRR 1.06, 95%CI 1.04-1.09) and SGA (1.23, 1.22-1.26) but inversely associated with LGA (0.83, 0.82-0.85), primary caesarean delivery (0.88, 0.87-0.90) and stillbirth (0.73, 0.53-0.99). Overweight was associated with increased risk of LGA (1.17, 1.14-1.19), primary caesarean delivery (1.18, 1.16-1.20) and stillbirth (1.44, 1.03-2.06), but inversely associated with SGA (0.92, 0.90-0.95) and shoulder dystocia or birth injury (0.86, 0.79-0.93). Obesity was associated with increased risk of PTB (1.12, 1.05-1.20), LGA (1.32, 1.27-1.37), primary caesarean delivery (1.45, 1.40-1.50), but inversely associated with SGA (0.92, 0.87-0.97). The aIRRs for underweight, overweight and obesity in relation to these adverse pregnancy outcomes ranged from 0.65 to 1.52 according to maternal age. In Chinese population, maternal pre-pregnancy BMI was significantly associated with the risk of adverse pregnancy outcomes and the risk differs according to maternal age. Further investigation is warranted to determine whether and how counselling and interventions for women with low or increased BMI before pregnancy can reduce the risk of adverse pregnancy outcomes.
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Project description:Childhood obesity is a major health problem in Mexico. Obesity prevalence estimated by body mass index (BMI) is almost half than that estimated by percent body fat (%BF) in the Childhood Obesity pediatric cohort (COIPIS). We performed a genome-wide association study (GWAS) of BMI and %BF in 828 children from the COIPIS to identify markers of predisposition to high values for both phenotypes used for obesity classification. For the GWAS we used the LAT Axiom 1, Affymetrix and 2.5 million single loci from the 1000 Genomes Phase 3 imputation panel. We used a linear model, adjusted by age, sex, and Amerindian ancestry assuming an additive inheritance model. Genome-wide significance (p ≤ 5.0 × 10-8) and 80% of statistical power was reached for associations of two loci in two genes (CERS3 and CYP2E1) to BMI. Also, 11 loci in six genes (ANKS1B, ARNTL2, KCNS3, LMNB1, SRGAP3, TRPC7) reached genome-wide significance for associations to %BF, though not 80% of statistical power. None of the SNPs were previously reported as being associated to BMI or %BF. In addition, different loci were found for BMI and %BF. These results highlight the importance of gaining deeper understanding of genetic markers of predisposition to high values for the phenotypes used for obesity diagnosis.
| S-EPMC6895864 | biostudies-literature
Project description:BACKGROUND:Prospective data are sparse for active commuting to work and body weight in Asia. We assessed the association of 5-year changes in commuting mode with body mass index (BMI) and the indicators of abdominal obesity in Japanese working adults. METHODS:In this longitudinal study, we studied 29,758 participants (25,808 men and 3950 women) in Japan aged 30 to 64?years at baseline who underwent further health examination 5?years after the baseline examination. Changes in BMI were calculated from objectively measured body height and weight at baseline and follow-up examination. Visceral and subcutaneous fat areas and waist circumference measured by computed tomography scans were used as indicators for abdominal adiposity. Linear regression was applied to estimate the association of changes in commuting mode with the obesity outcomes. RESULTS:Within the 5-year study period, adults who maintained inactive commuting gained weight, and compared with this group, adults who switched to inactive commuting had higher weight gain; conversely, adults who switched to active or public transportation commuting and especially those who maintained active or public transportation commuting experienced less weight gain. Subgroup analysis showed similar tendency across the different transitions of leisure-time exercise or occupational physical activity. For example, among adults who maintained no exercise (n?=?16,087), the adjusted mean (95% confidence intervals) of the BMI change over 5?years in kg/m2 were 0.27 (0.24 to 0.30) for maintained inactive commuting group (reference), 0.34 (0.30 to 0.38) for switching to inactive commuting group (P?=?0.046), 0.20 (0.18 to 0.22) for switching to active commuting or public transportation group (P?=?0.001), and 0.09 (0.06 to 0.13) for maintained active commuting or public transportation group (P?<?0.001). Maintained inactive commuting tended to be associated with larger gain in abdominal adiposity indicators. CONCLUSION:Switching from inactive commuting mode to more physically active commuting mode and maintaining active commuting can promote body weight control among working adults across different levels of occupational or leisure-time physical activity.
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Project description:Outcomes related to disordered metabolism are common in alcohol dependence (AD). To investigate alterations in the regulation of body mass that occur in the context of AD, we performed a genome-wide association study (GWAS) of body mass index (BMI) in African Americans (AAs) and European Americans (EAs) with AD. Subjects were recruited for genetic studies of AD or drug dependence and evaluated using the Semi-structured Assessment for Drug Dependence and Alcoholism. We investigated a total of 2587 AAs and 2959 EAs with DSM-IV AD diagnosis. In the stage 1 sample (N = 4137), we observed three genome-wide significant (GWS) single-nucleotide polymorphism associations, rs200889048 (P = 8.98 * 10-12 ) and rs12490016 (P = 1.44 * 10-8 ) in EAs and rs1630623 (P = 5.14 * 10-9 ) in AAs and EAs meta-analyzed. In the stage 2 sample (N = 1409), we replicated 278, 253 and 168 of the stage 1 suggestive loci (P < 5*10-4 ) in AAs, EAs, and AAs and EAs meta-analyzed, respectively. A meta-analysis of stage 1 and stage 2 samples (N = 5546) identified two additional GWS signals: rs28562191 in EAs (P = 4.46 * 10-8 ) and rs56950471 in AAs (P = 1.57 * 10-9 ). Three of the GWS loci identified (rs200889048, rs12490016 and rs1630623) were not previously reported by GWAS of BMI in the general population, and two of them raise interesting hypotheses: rs12490016-a regulatory variant located within LINC00880, where there are other GWAS-identified variants associated with birth size, adiposity in newborns and bulimia symptoms, which also interact with social stress in relation to birth size; rs1630623-a regulatory variant related to ALDH1A1, a gene involved in alcohol metabolism and adipocyte plasticity. These loci offer molecular insights regarding the regulatory mechanisms of body mass in the context of AD.
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Project description:Background/objectivesThe relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study.Subjects/methodsThe Sister Study is a cohort of 50 884 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment. Study participants completed examinations which included measurements of height and weight, and provided blood samples. Blood DNA methylation data generated with the Illumina Infinium HumanMethylation27 BeadChip array covering 27,589 CpG sites was available for 871 women from a prior study of breast cancer and DNA methylation. To identify differentially methylated CpG sites associated with BMI, we analyzed this methylation data using robust linear regression with adjustment for age and case status. For those CpGs passing the false discovery rate significance level, we examined the association in a replication set comprised of a non-overlapping group of 187 women from the Sister Study who had DNA methylation data generated using the Infinium HumanMethylation450 BeadChip array. Analysis of this expanded 450 K array identified additional BMI-associated sites which were investigated with targeted pyrosequencing.ResultsFour CpG sites reached genome-wide significance (false discovery rate (FDR) q<0.05) in the discovery set and associations for all four were significant at strict Bonferroni correction in the replication set. An additional 23 sites passed FDR in the replication set and five were replicated by pyrosequencing in the discovery set. Several of the genes identified including ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2 and CRHR2 have been linked to obesity and obesity-related chronic diseases.ConclusionsOur findings support the hypothesis that obesity-related epigenetic differences are detectable in blood and may be related to risk of chronic disease.
| S-EPMC5209267 | biostudies-literature
Project description:ObjectivesThe objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs).DesignThis was a prospective cohort study.SettingThis study was conducted in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai, China.Primary and secondary outcome measuresA cohort study involving a total of 2174 pregnant women was conducted. Each participant was followed to record weekly weight gain and pregnancy outcomes. The Institute of Medicine classification was used to categorise prepregnancy BMI, and four GWG trajectories were identified using a latent class growth model.ResultsThe adjusted ORs for the risks of large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) were significantly greater for women with prepregnancy overweight/obesity (OR=1.77, 2.13, 1.95 and 4.24; 95% CI 1.3 to 2.42, 1.32 to 3.46, 1.43 to 2.66 and 2.01 to 8.93, respectively) and lower for those who were underweight than for those with normal weight (excluding HDP) (OR=0.35, 0.27 and 0.59; 95% CI 0.22 to 0.53, 0.11 to 0.66 and 0.36 to 0.89, respectively). The risk of small for gestational age (SGA) and low birth weight (LBW) was significantly increased in the underweight group (OR=3.11, 2.20; 95% CI 1.63 to 5.92, 1.10 to 4.41; respectively) compared with the normal-weight group; however, the risk did not decrease in the overweight/obese group (p=0.942, 0.697, respectively). GWG was divided into four trajectories, accounting for 16.6%, 41.4%, 31.7% and 10.3% of the participants, respectively. After adjustment for confounding factors, the risk of LGA was 1.54 times greater for women in the slow GWG trajectory group than for those in the extremely slow GWG trajectory group (95% CI 1.07 to 2.21); the risk of SGA and LBW was 0.37 times and 0.46 times lower for women in the moderate GWG trajectory group and 0.14 times and 0.15 times lower for women in the rapid GWG trajectory group, respectively; the risk of macrosomia and LGA was 2.65 times and 2.70 times greater for women in the moderate GWG trajectory group and 3.53 times and 4.36 times greater for women in the rapid GWG trajectory group, respectively; and the women in the other three trajectory groups had a lower risk of GDM than did those in the extremely slow GWG trajectory group, but there was not much variation in the ORs. Notably, different GWG trajectories did not affect the risk of HDP.ConclusionsAs independent risk factors, excessively high and low prepregnancy BMI and GWG can increase the risk of APOs.
| S-EPMC10989183 | biostudies-literature
Project description:Human height and body mass index are influenced by a large number of genes, each with small effects, along with environment. To identify common genetic variants associated with these traits, we performed genome-wide association studies in 11,536 individuals composed of Australian twins, family members, and unrelated individuals at approximately 550,000 genotyped SNPs. We identified a single genome-wide significant variant for height (P value=1.06x10(-9)) located in HHIP, a well-replicated height-associated gene. Suggestive levels of association were found for other known genes associated with height (P values<1x10(-6)): ADAMTSL3, EFEMP1, GPR126, and HMGA2; and BMI (P values<1x10(-4)): FTO and MC4R. Together, these variants explain less than 2% of total phenotypic variation for height and 0.5% for BMI.
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