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Liu C.-T.,Boston University | Monda K.L.,University of North Carolina at Chapel Hill | Taylor K.C.,University of North Carolina at Chapel Hill | Taylor K.C.,University of Louisville | And 84 more authors.
PLoS Genetics | Year: 2013

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10-6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10-8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10-8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10-8; RREB1: p = 5.7×10-8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.

Ye E.Q.,Center for Metabolic Disease Prevention | Chacko S.A.,Center for Metabolic Disease Prevention | Chou E.L.,Center for Metabolic Disease Prevention | Kugizaki M.,University of California at Los Angeles | Liu S.,Center for Metabolic Disease Prevention
Journal of Nutrition | Year: 2012

Whole-grain and high fiber intakes are routinely recommended for prevention of vascular diseases; however, there are no comprehensive and quantitative assessments of available data in humans. The aim of this study was to systematically examine longitudinal studies investigating whole-grain and fiber intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease (CVD), weight gain, and metabolic risk factors. We identified 45 prospective cohort studies and 21 randomized-controlled trials (RCT) between 1966 and February 2012 by searching the Cumulative Index to Nursing and Allied Health Literature, Cochrane, Elsevier Medical Database, and PubMed. Study characteristics, whole-grain and dietary fiber intakes, and risk estimates were extracted using a standardized protocol. Using random effects models, we found that compared with never/rare consumers of whole grains, those consuming 48-80 g whole grain/d (3-5 serving/d) had an ~26% lower risk of T2D [RR = 0.74 (95% CI: 0.69, 0.80)], ~21% lower risk of CVD [RR = 0.79 (95% CI: 0.74, 0.85)], and consistently less weight gain during 8-13 y (1.27 vs 1.64 kg; P = 0.001). Among RCT, weighted mean differences in postintervention circulating concentrations of fasting glucose and total and LDL-cholesterol comparing whole-grain intervention groups with controls indicated significantly lower concentrations after whole-grain interventions [differences in fasting glucose:20.93mmol/L (95%CI:21.65,20.21), total cholesterol:20.83mmol/L (21.24,20.42); and LDL-cholesterol:20.72 mmol/L (21.34,20.11)]. Findings fromthismeta-analysis provide evidence to support beneficial effects ofwhole-grain intake on vascular disease prevention. Potential mechanisms responsible for whole grains' effects on metabolic intermediates require further investigation in large intervention trials. © 2012 American Society for Nutrition.

Millen A.E.,State University of New York at Buffalo | Wactawski-Wende J.,State University of New York at Buffalo | Pettinger M.,Fred Hutchinson Cancer Research Center | Melamed M.L.,Yeshiva University | And 6 more authors.
American Journal of Clinical Nutrition | Year: 2010

Background: It is unclear how well surrogate markers for vitamin D exposure (eg, oral intake of vitamin D and estimates of sunlight exposure), with and without consideration of other potential predictors of 25-hydroxyvitamin D [25(OH)D] concentrations, similarly rank individuals with respect to 25(OH)D blood concentrations. Objective: The objective was to determine how much variation in serum 25(OH)D concentrations (nmol/L) could be explained by a predictive model with the use of different vitamin D surrogate markers (latitude of residence, mean annual regional solar irradiance estimates, and oral sources) and other individual characteristics that might influence vitamin D status. Design: A random sample of 3055 postmenopausal women (aged 50-70 y) participating in 3 nested case-control studies of the Women's Health Initiative Calcium plus Vitamin D Clinical Trial was used. Serum 25(OH)D values, assessed at year 1 (1995-2000), and potential predictors of 25(OH)D concentrations, assessed at year 1 or Women's Health Initiative baseline (1993-1998), were used. Results: More than half of the women (57.1%) had deficient (<50 nmol/L) concentrations of 25(OH)D. Distributions of 25(OH)D concentrations by level of latitude of residence, mean annual regional solar irradiance, and intake of vitamin D varied considerably. The predictive model for 25(OH)D explained 21% of the variation in 25(OH)D concentrations. After adjustment for month of blood draw, breast cancer status, colorectal cancer status, fracture status, participation in the hormone therapy trial, and randomization to the dietary modification trial, the predictive model included total vitamin D intake from foods and supplements, waist circumference, recreational physical activity, race-ethnicity, regional solar irradiance, and age. Conclusions: Surrogate markers for 25(OH)D concentrations, although somewhat correlated, do not adequately reflect serum vitamin D measures. These markers and predictive models of blood 25(OH)D concentrations should not be given as much weight in epidemiologic studies of cancer risk. © 2010 American Society for Nutrition.

Li H.,CAS Shanghai Institutes for Biological Sciences | Kilpelainen T.O.,Addenbrookes Hospital | Liu C.,CAS Shanghai Institutes for Biological Sciences | Zhu J.,CAS Shanghai Institutes for Biological Sciences | And 61 more authors.
Diabetologia | Year: 2012

Aims/hypothesis FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. Methods All studies published on the association between FTO-rs9939609 (or proxy [r2>0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. Results The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p=9.0×10 -19), overweight by 1.13-fold/allele (p=1.0×10 -11) and type 2 diabetes by 1.15-fold/allele (p=5.5×10 -8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p=6.6×10 -5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m 2 per allele (p=2.8×10 -17), WHR by 0.003/allele (p=1.2×10 -6), and body fat percentage by 0.31%/allele (p=0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. Conclusions/interpretation FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI. © 2012 Springer-Verlag.

Song Y.,Harvard University | Klevak A.,Harvard University | Manson J.E.,Harvard University | Buring J.E.,Harvard University | And 3 more authors.
Diabetes Research and Clinical Practice | Year: 2010

Background: Chronic airway inflammation in asthma or chronic obstructive pulmonary disease (COPD) may be involved in the pathogenesis of type 2 diabetes; however, prospective data have been limited. Methods: A prospective cohort of 38,570 women who were aged ≥45 years, free of cardiovascular disease and cancer at baseline, and free of diabetes at baseline and in the first 12 months were analyzed. We classified all women into three groups according to the presence and absence of self-reported asthma or COPD (including emphysema, chronic bronchitis, and bronchiectasis). Results: During a median follow-up of 12.2 years, 2472 incident type 2 diabetes events were documented. Women who had ever reported asthma or COPD were associated with an increased diabetes risk; the multivariate RRs were 1.37 (95% CI, 1.20-1.57) for women who had asthma alone and 1.38 (95% CI, 1.14-1.67) for COPD without asthmatic symptoms. Furthermore, these associations were not significantly modified by age, smoking status, physical activity, BMI, alcohol intake, hormone replacement therapy, menopausal status or randomized treatment. Conclusions: Asthma and COPD were individually and independently associated with an increased risk of type 2 diabetes in women, indicating that chronic airway inflammation may contribute to diabetes pathogenesis. © 2010 Elsevier Ireland Ltd.

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