Publications

Abstract Although hundreds of genome-wide association studies-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 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (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 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 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 with 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 10 single nucleotide polymorphisms (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.

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTSurface-Initiated Ring-Opening Metathesis Polymerization on Si/SiO2Namyong Y. Kim, Noo Li Jeon, Insung S. Choi, Seiichi Takami, Yoshiko Harada, Krista R. Finnie, Gregory S. Girolami, Ralph G. Nuzzo, George M. Whitesides, and Paul E. LaibinisView Author Information Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, Department of Chemistry and the Seitz Materials Research Laboratory, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, and Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Cite this: Macromolecules 2000, 33, 8, 2793–2795Publication Date (Web):March 31, 2000Publication History Received11 January 2000Published online31 March 2000Published inissue 1 April 2000https://pubs.acs.org/doi/10.1021/ma000046chttps://doi.org/10.1021/ma000046crapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views1938Altmetric-Citations131LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Catalysts,Polymer films,Polymers,Silicon,Thickness Get e-Alerts

Plasma fetuin-A is associated with type 2 diabetes, and AHSG, the gene encoding fetuin-A, has been identified as a susceptibility locus for diabetes and metabolic syndrome. Thus far, unbiased investigations of the genetic determinants of plasma fetuin-A concentrations have not been conducted. We searched for single nucleotide polymorphisms (SNPs) related to fetuin-A concentrations by a genome-wide association study in six population-based studies. We examined the association of fetuin-A levels with ∼ 2.5 million genotyped and imputed SNPs in 9,055 participants of European descent and 2,119 African Americans. In both ethnicities, the strongest associations were centered in a region with a high degree of LD near the AHSG locus. Among 136 genome-wide significant (P < 0.05 × 10-8) SNPs near the AHSG locus, the top SNP was rs4917 (P =1.27 × 10-303), a known coding SNP in exon 6 that is associated with a 0.06 g/l (∼13%) lower fetuin-A level. This variant alone explained 14% of the variation in fetuin-A levels. Analyses conditioned on rs4917 indicated that the strong association with the AHSG locus stems from additional independent associations of multiple variants among European Americans. In conclusion, levels of fetuin-A in plasma are strongly associated with SNPs in its encoding gene, AHSG, but not elsewhere in the genome. Given the strength of the associations observed for multiple independent SNPs, the AHSG gene is an example of a candidate locus suitable for additional investigations including fine mapping to elucidate the biological basis of the findings and further functional experiments to clarify AHSG as a potential therapeutic target.

Abstract Background A high proportion of women start pregnancy overweight/obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives, and, thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) with offspring systemic metabolite profile are causal via intrauterine mechanisms or familial factors. Methods and Findings We used one and two-stage individual participant data (IPD) metaanalysis, and a negative-control (paternal BMI) to examine the association between maternal prepregnancy BMI and offspring serum metabolome from three European birth cohorts (offspring age at metabolite assessment 16, 17 and 31 years). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from one-stage IPD meta-analysis ( N =5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with VLDL-lipoproteins, VLDL-C, VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with HDL-lipoprotein, HDL-diameter, HDL-C, HDL 2 -C and HDL 3 -C (all P&lt;0.003). Stronger magnitudes of associations were present for maternal compared with paternal BMI across these associations, however there was no strong statistical evidence for heterogeneity between them (all bootstrap P &gt;0.003, equivalent to 0.05 after accounting for multiple testing). Results were similar in each individual cohort, and in the two-stage analysis. Offspring BMI showed similar patterns of crosssectional association with metabolic profiles as for parental pre-pregnancy BMI associations, but with greater magnitudes. Adjustment of the parent BMI-offspring metabolite associations for offspring BMI suggested the parental associations were largely due to the association of parental BMI measures with offspring BMI. Conclusion Our findings suggest that maternal BMI-offspring metabolome associations are likely to be largely due to shared genetic or familial lifestyle confounding, rather than intrauterine programming mechanisms. They do not support the introduction of measures to reduce maternal BMI in order to prevent adverse offspring cardio-metabolic health.

Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown.

The prevalence of overweight or obesity and gestational diabetes mellitus (GDM) is increasing and is a major public health concern. Maternal risk factors for development of diabetes in later life include GDM and overweight during pregnancy. Overweight is a strong risk factor for GDM, and the occurrence of both increases the risk for subsequent metabolic syndrome. Little data are available on the risk of diabetes and metabolic diseases in women with normal glucose tolerance during pregnancy, who have risk factors for GDM. Moreover, few studies have investigated the individual contribution of overweight and GDM during pregnancy to the risk of diabetes and hypertension in later life. This prospective population-based study evaluated prepregnancy overweight and GDM as determinants of risk for diabetes and hypertension, separately and in combination, 20 years after pregnancy. Population-based cohort data from the Northern Finland Birth Cohort 1986 were linked with register-based data on diagnosis of diabetes and hypertension obtained from records on reimbursement of medical expenses and diagnoses at hospital discharge. The oral glucose tolerance test (OGTT) was used to diagnose GDM. Several categories of risk were evaluated for diabetes and hypertension (which were the primary study outcomes). These included: (1) normal weight women with GDM (n = 70); (2) overweight women with GDM (n = 54); (3) normal-weight (n = 768); (4) overweight (n = 250) women with risk factors for GDM but normal OGTT results; and (5) women with no risk factors for GDM (n = 5341). Calculation of the population-attributable fractions (PAFs) estimated the cumulative incidence of diabetes and hypertension associated with prepregnancy overweight. Analysis of time-to-event curves showed that the cumulative incidence of diabetes and hypertension diagnosed in the whole study population was 1.3% and 7.5%, respectively. Women with concomitant prepregnancy overweight and GDM were at extremely high risk of diabetes (hazard ratio [HR], 47.24; PAF, 15.8%) and hypertension (HR, 9.16; PAF, 4.4%). The occurrence of prepregnancy overweight in women with a normal OGTT during pregnancy was associated with increased risk of diabetes (HR, 12.63; PAF, 22.2%) and hypertension (HR, 2.86; PAF, 6.0%), whereas a finding of GDM only among women with prepregnancy normal weight was associated with increased risk of diabetes (HR, 10.61; PAF, 5.2%) but not hypertension. These findings show that prepregnancy overweight is a critical risk factor for development of diabetes and hypertension 20 years after delivery. Overweight combined with even mild GDM markedly increases the risks of these diseases.

Women who developed gestational diabetes mellitus represent a high-risk population for hypertension later in life. The role of diet in the progression of hypertension among this susceptible population is unknown. We conducted a prospective cohort study of 3818 women with a history of gestational diabetes mellitus in the Nurses’ Health Study II as part of the ongoing Diabetes &amp; Women’s Health Study. These women were followed-up from 1989 to 2011. Incident hypertension was identified through self-administered questionnaires that were validated previously by medical record review. Adherence scores for the alternative Healthy Eating Index 2010, the alternative Mediterranean diet, and the Dietary Approaches to Stop Hypertension were computed for each participant. Cox proportional hazard models were used to evaluate the associations between dietary scores and hypertension while adjusting for major risk factors for hypertension. We documented 1069 incident hypertension cases during a median of 18.5 years of follow-up. After adjustment for major risk factors for hypertension, including body mass index, alternative Healthy Eating Index 2010, alternative Mediterranean diet, and Dietary Approaches to Stop Hypertension scores were significantly inversely associated with the risk of hypertension; hazard ratio and 95% confidence interval comparing the extreme quartiles (highest versus lowest) were 0.76 (0.61–0.94; P for linear trend =0.03) for AHEI score, 0.72 (0.58–0.90; P for trend =0.01) for Dietary Approach to Stop Hypertension score, and 0.70 (0.56–0.88; P for trend =0.002) for alternative Mediterranean diet score. Adherence to a healthful dietary pattern was related to a lower subsequent risk of developing hypertension among women with a history of gestational diabetes mellitus.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

OBJECTIVE We examined the association of lactation duration with incident type 2 diabetes among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We monitored 4,372 women with a history of GDM participating in the Nurses’ Health Study II for incident type 2 diabetes over 25 years up to 2017. Lactation history was obtained through follow-up questionnaires to calculate lactation duration. Follow-up blood samples were collected from a subset of these women at median age of 58 years through the Diabetes &amp; Women’s Health Study. RESULTS We documented 873 incident cases of type 2 diabetes during 87,411 person-years of follow-up. Longer duration of lactation was associated with lower risk of type 2 diabetes for both total lactation (hazard ratio 1.05 [95% CI 0.83–1.34] for up to 6 months, 0.91 [0.72–1.16] for 6–12 months, 0.85 [0.67–1.06] for 12–24 months, and 0.73 [0.57–0.93] for &amp;gt;24 months, compared with 0 months; P-trend = 0.003) and exclusive breastfeeding (P-trend = 0.002) after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy BMI. Longer duration of lactation was also associated with lower HbA1c, fasting plasma insulin, and C-peptide concentrations among women without type 2 diabetes at follow-up (all adjusted P-trend ≤0.04). CONCLUSIONS Longer duration of lactation is associated with a lower risk of type 2 diabetes and a favorable glucose metabolic biomarker profile among women with a history of GDM. The underlying mechanisms and impact on diabetes complications, morbidity, and mortality remain to be determined.