Evidence for Association between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults: The Add Health Study

Glycated hemoglobin (HbA1c) is used to classify glycaemia and type 2 diabetes (T2D). Body mass index (BMI) is a predictor of HbA1c levels and T2D. We tested 43 established BMI and obesity loci for association with HbA1c in a nationally representative multiethnic sample of young adults from the National Longitudinal Study of Adolescent to Adult Health [Add Health: age 24–34 years; n = 5641 European Americans (EA); 1740 African Americans (AA); 1444 Hispanic Americans (HA)] without T2D, using two levels of covariate adjustment (Model 1: age, sex, smoking, and geographic region; Model 2: Model 1 covariates plus BMI). Bonferroni adjustment was made for 43 SNPs and we considered P < 0.0011 statistically significant. Means (SD) for HbA1c were 5.4% (0.3) in EA, 5.7% (0.4) in AA, and 5.5% (0.3) in HA. We observed significant evidence for association with HbA1c for two variants near SH2B1 in EA (rs4788102, P = 2.2 × 10−4; rs7359397, P = 9.8 × 10−4) for Model 1. Both results were attenuated after adjustment for BMI (rs4788102, P = 1.7 × 10−3; rs7359397, P = 4.6 × 10−3). No variant reached Bonferroni-corrected significance in AA or HA. These results suggest that SH2B1 polymorphisms are associated with HbA1c, largely independent of BMI, in EA young adults

Moderate to vigorous physical activity interactions with genetic variants and body mass index in a large US ethnically diverse cohort

Summary What is already known about this subject Genome-Wide Association Studies have successfully identified numerous genetic loci that influence body mass index in European-descent middle-aged adults. Adolescence is a high-risk period for the development of adult obesity and severe obesity. Physical activity is one of the most promising behavioural candidates for preventing and reducing weight gain, particularly among youth. What this study adds An examination of the joint association between 41 of the well-established obesity susceptibility single-nucleotide polymorphisms with <5 vs. ≥5 bouts of moderate to vigorous physical activity (MVPA) per week in relation to body mass index (BMI)-for-age Z-score in a nationally representative sample of European American, African-American and Hispanic American adolescents. Three nominally significant interactions (P < 0.05) varied by race/ethnicity. Overall, the estimated effect of the risk allele on BMI-for-age Z-score was greater in individuals with <5 than those with ≥5 bouts MVPA per week. Background Little is known about the interaction between genetic and behavioural factors during lifecycle risk periods for obesity and how associations vary across race/ethnicity. Objective The objective of this study was to examine joint associations of adiposity-related single-nucleotide polymorphisms (SNPs) and moderate to vigorous physical activity (MVPA) with body mass index (BMI) in a diverse adolescent cohort. Methods Using data from the National Longitudinal Study of Adolescent Health (n = 8113: Wave II 1996; ages 12-21, Wave III; ages 18-27), we assessed interactions of 41 well-established SNPs and MVPA with BMI-for-age Z-scores in European Americans (EA; n = 5077), African-Americans (AA; n = 1736) and Hispanic Americans (HA; n = 1300). Results Of 97 assessed, we found nominally significant SNP-MVPA interactions on BMI-for-age Z-score in EA at GNPDA2 and FTO and in HA at LZTR2/SEC16B. In EA, the estimated effect of the FTO risk allele on BMI-for-age Z-score was lower (β = -0.13; 95% confidence interval [CI]: 0.08, 0.18) in individuals with ≥5 vs. <5 (β = 0.24; CI: 0.16, 0.32) bouts of MVPA per week (P for interaction 0.02). Race/ethnicity-pooled meta-analysis showed nominally significant interactions for SNPs at TFAP2B, POC5 and LYPLAL1. Conclusions High MVPA may attenuate underlying genetic risk for obesity during adolescence, a high-risk period for adult obesity

Screen time behaviours may interact with obesity genes, independent of physical activity, to influence adolescent BMI in an ethnically diverse cohort

Background There has been little investigation of gene-by-environment interactions related to sedentary behaviour, a risk factor for obesity defined as leisure screen time (ST; i.e. television, video and computer games). Objective To test the hypothesis that limiting ST use attenuates the genetic predisposition to increased body mass index (BMI), independent of physical activity. Design Using 7642 wave II participants of the National Longitudinal Study of Adolescent Health, (Add Health; mean=16.4 years, 52.6% female), we assessed the interaction of ST (hweek-1) and 41 established obesity single nucleotide polymorphisms (SNPs) with age- and sex-specific BMI Z-scores in 4788 European-American (EA), 1612 African-American (AA) and 1242 Hispanic American (HA) adolescents. Results Nominally significant SNP ST interaction were found for FLJ35779 in EA, GNPDA2 in AA and none in HA (EA: beta [SE]=0.016[0.007]), AA: beta [SE]=0.016[0.011]) per 7hweek-1 ST and one risk allele in relation to BMI Z-score. Conclusions While for two established BMI loci, we find evidence that high levels of ST exacerbate the influence of obesity susceptibility variants on body mass; overall, we do not find strong evidence for interactions between the majority of established obesity loci. However, future studies with larger sample sizes, or that may build on our current study and the growing published literature, are clearly warranted

Genome-wide Association Study of Periodontal Pathogen Colonization

Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom “checkerboard” DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: “high red” and “high orange” bacterial complexes, and “high” Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10−8). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10−6) of association. All associations reported for “red” and “orange” complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P&lt;5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis

Acute Administration of the GLP-1 Receptor Agonist Lixisenatide Diminishes Postprandial Insulin Secretion in Healthy Subjects But Not in Type 2 Diabetes, Associated with Slowing of Gastric Emptying

Published online 22 April 2022Introduction: It is uncertain whether lixisenatide has postprandial insulinotropic effects when its effect on slowing gastric emptying is considered, in healthy subjects and type 2 diabetes mellitus (T2DM). We evaluated the effects of single administration of 10 lg sc lixisenatide on glycaemia, insulin secretion and gastric emptying (GE), measured using the ‘gold standard’ technique of scintigraphy following an oral glucose load (75 g glucose). Methods: Fifteen healthy subjects (nine men, six women; age 67.2 ± 2.3 years) and 15 patients with T2DM (nine men, six women; age 61.9 ± 2.3 years) had measurements of GE, plasma glucose, insulin and C-peptide for 180 min after a radiolabeled 75 g glucose drink on two separate days. All subjects received lixisenatide (10 lg sc) or placebo in a randomised, double-blind, crossover fashion 30 min before the drink. Insulin secretory response (ISR) was determined using the C-peptide deconvolution method. Results: GE was markedly slowed by lixisenatide compared with placebo in both healthy subjects (1.45 ± 0.10 kcal/min for placebo vs. 0.60 ± 0.14 kcal/min for lixisenatide) and diabetes (1.57 ± 0.06 kcal/min for placebo vs. 0.75 ± 0.13 kcal/min for lixisenatide) (both P\0.001) with no difference between the two groups (P = 0.42). There was a moderate to strong inverse correlation between the early insulin secretory response calculated at 60 min and gastric retention at 60 min with lixisenatide treatment in healthy subjects (r = - 0.8, P = 0.0003) and a trend in type 2 diabetes (r = - 0.4, P = NS), compared with no relationships in the placebo arms (r = - 0.02, P = NS, healthy subjects) and (r = - 0.16, P = NS, type 2 diabetes). Conclusion: The marked slowing of GE of glucose induced by lixisenatide is associated with attenuation in the rise of postprandial glucose in both healthy subjects and diabetes and early insulin secretory response in healthy subjects.Chinmay S. Marathe . Hung Pham . Tongzhi Wu . Laurence G. Trahair . Rachael S. Rigda . Madeline D. M. Buttfield . Seva Hatzinikolas . Kylie Lange . Christopher K. Rayner . Andrea Mari . Michael Horowitz . Karen L. Jone

Parity Violation Constraints Using Cosmic Microwave Background Polarization Spectra from 2006 and 2007 Observations by the QUaD Polarimeter

We constrain parity-violating interactions to the surface of last scattering using spectra from the QUaD experiment’s second and third seasons of observations by searching for a possible systematic rotation of the polarization directions of cosmic microwave background photons. We measure the rotation angle due to such a possible ‘‘cosmological birefringence’’ to be $0.55^{\circ} \pm 0.82^{\circ}$ (random) $\pm 0.5^{\circ}$ (systematic) using QUaD’s 100 and 150 GHz temperature-curl and gradient-curl spectra over the spectra over the multipole range 200 <$\ell$< 2000, consistent with null, and constrain Lorentz-violating interactions to <2 $\times$ 10$^ {-43}$ GeV (68% confidence limit). This is the best constraint to date on electrodynamic parity violation on cosmological scales.Astronom

Second and Third Season QUaD Cosmic Microwave Background Temperature and Polarization Power Spectra

We report results from the second and third seasons of observation with the QUaD experiment. Angular power spectra of the cosmic microwave background are derived for both temperature and polarization at both 100 GHz and 150 GHz, and as cross-frequency spectra. All spectra are subjected to an extensive set of jackknife tests to probe for possible systematic contamination. For the implemented data cuts and processing technique such contamination is undetectable. We analyze the difference map formed between the 100 and 150 GHz bands and find no evidence of foreground contamination in polarization. The spectra are then combined to form a single set of results which are shown to be consistent with the prevailing LCDM model. The sensitivity of the polarization results is considerably better than that of any previous experiment— for the first time multiple acoustic peaks are detected in the E-mode power spectrum at high significance

The QUAD Galactic Plane Survey 1: Maps and Analysis of Diffuse Emission

We present a survey of ~ 800 square degrees of the galactic plane observed with the QUaD telescope. The primary product of the survey are maps of Stokes I, Q and U parameters at 100 and 150 GHz, with spatial resolution 5 and 3.5 arcminutes respectively. Two regions are covered, spanning approximately 245 - 295° and 315 - 5° in galactic longitude l, and -4 < b < +4° in galactic latitude b. At 0:02° square pixel size, the median sensitivity is 74 and 107 kJy/sr at 100 GHz and 150 GHz respectively in I, and 98 and 120 kJy/sr for Q and U. In total intensity, we find an average spectral index of α = 2:35+-0:01(stat)+-0:02(sys) for |b| ≤1°, indicative of emission components other than thermal dust. A comparison to published dust, synchrotron and free-free models implies an excess of emission in the 100 GHz QUaD band, while better agreement is found at 150 GHz. A smaller excess is observed when comparing QUaD 100 GHz data to WMAP 5-year W band; in this case the excess is likely due to the wider bandwidth of QUaD. Combining the QUaD and WMAP data, a two-component spectral fit to the inner galactic plane (|b| ≤1°) yields mean spectral indices of αs = -0:32+-0:03 and αd = 2:84+-0:03; the former is interpreted as a combination of the spectral indices of synchrotron, free-free and dust, while the second is attributed largely to the thermal dust continuum. In the same galactic latitude range, the polarization data show a high degree of alignment perpendicular to the expected galactic magnetic field direction, and exhibit mean polarization fraction 1:38+-0:08(stat)+-0:1(sys)% at 100 GHz and 1:70+-0:06(stat)+-0:1(sys)% at 150 GHz. We find agreement in polarization fraction between QUaD 100 GHz and WMAP W band, the latter giving 1:1+-0:4%

Viking Age garden plants from southern Scandinavia: diversity, taphonomy and cultural aspects

Plant finds recovered from archaeological sites in southern Scandinavia dated to the Viking Age reflect the diversity of useful plants that were cultivated and collected. This review presents the results of 14 investigations of deposits that are dated between AD 775 and 1050. The site types are categorized as agrarian, urban, military and burials. Garden plants are unevenly distributed, as the greatest diversity is recorded in features from urban contexts. We argue that taphonomic processes played an important role in the picture displayed. Archaeobotanical research results from neighbouring regions suggest that Viking Age horticulture has its roots in older traditions, and that the spectrum of garden plants is influenced by central and north-western European horticultural customs, which were to a great extent shaped by Roman occupation