Sugar-sweetened beverages and genetic risk of obesity Qi, Qibin; Chu, Audrey Y; Kang, Jae H ...
New England journal of medicine/The New England journal of medicine,
10/2012, Letnik:
367, Številka:
15
Journal Article
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Temporal increases in the consumption of sugar-sweetened beverages have paralleled the rise in obesity prevalence, but whether the intake of such beverages interacts with the genetic predisposition ...to adiposity is unknown.
We analyzed the interaction between genetic predisposition and the intake of sugar-sweetened beverages in relation to body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) and obesity risk in 6934 women from the Nurses' Health Study (NHS) and in 4423 men from the Health Professionals Follow-up Study (HPFS) and also in a replication cohort of 21,740 women from the Women's Genome Health Study (WGHS). The genetic-predisposition score was calculated on the basis of 32 BMI-associated loci. The intake of sugar-sweetened beverages was examined prospectively in relation to BMI.
In the NHS and HPFS cohorts, the genetic association with BMI was stronger among participants with higher intake of sugar-sweetened beverages than among those with lower intake. In the combined cohorts, the increases in BMI per increment of 10 risk alleles were 1.00 for an intake of less than one serving per month, 1.12 for one to four servings per month, 1.38 for two to six servings per week, and 1.78 for one or more servings per day (P<0.001 for interaction). For the same categories of intake, the relative risks of incident obesity per increment of 10 risk alleles were 1.19 (95% confidence interval CI, 0.90 to 1.59), 1.67 (95% CI, 1.28 to 2.16), 1.58 (95% CI, 1.01 to 2.47), and 5.06 (95% CI, 1.66 to 15.5) (P=0.02 for interaction). In the WGHS cohort, the increases in BMI per increment of 10 risk alleles were 1.39, 1.64, 1.90, and 2.53 across the four categories of intake (P=0.001 for interaction); the relative risks for incident obesity were 1.40 (95% CI, 1.19 to 1.64), 1.50 (95% CI, 1.16 to 1.93), 1.54 (95% CI, 1.21 to 1.94), and 3.16 (95% CI, 2.03 to 4.92), respectively (P=0.007 for interaction).
The genetic association with adiposity appeared to be more pronounced with greater intake of sugar-sweetened beverages. (Funded by the National Institutes of Health and others.).
The 2015-2020 Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with ...long-term risk of cardiovascular disease (CVD).
To examine the associations of dietary scores for 4 healthy eating patterns with risk of incident CVD.
Prospective cohort study of initially healthy women from the Nurses' Health Study (NHS) (1984-2016) and the NHS II (1991-2017) and men from the Health Professionals Follow-up Study (HPFS) (1986-2012). The dates of analysis were July 25 to December 4, 2019.
Healthy Eating Index-2015 (HEI-2015), Alternate Mediterranean Diet Score (AMED), Healthful Plant-Based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI).
Cardiovascular disease events, including fatal and nonfatal coronary heart disease (CHD) and stroke.
The final study sample included 74 930 women in the NHS (mean SD baseline age, 50.2 7.2 years), 90 864 women in the NHS II (mean SD baseline age, 36.1 4.7 years), and 43 339 men in the HPFS (mean SD baseline age, 53.2 9.6 years). During a total of 5 257 190 person-years of follow-up, 23 366 incident CVD cases were documented (18 092 CHD and 5687 stroke) (some individuals were diagnosed as having both CHD and stroke). Comparing the highest with the lowest quintiles, the pooled multivariable-adjusted hazard ratios (HRs) of CVD were 0.83 (95% CI, 0.79-0.86) for the HEI-2015, 0.83 (95% CI, 0.79-0.86) for the AMED, 0.86 (95% CI, 0.82-0.89) for the HPDI, and 0.79 (95% CI, 0.75-0.82) for the AHEI (P for trend <.001 for all). In addition, a 25-percentile higher dietary score was associated with 10% to 20% lower risk of CVD (pooled HR, 0.80 95% CI, 0.77-0.83 for the HEI-2015; 0.90 95% CI, 0.87-0.92 for the AMED; 0.86 95% CI, 0.82-0.89 for the HPDI; and 0.81 95% CI, 0.78-0.84 for the AHEI). These dietary scores were statistically significantly associated with lower risk of both CHD and stroke. In analyses stratified by race/ethnicity and other potential risk factors for CVD, the inverse associations between these scores and risk of CVD were consistent in most subgroups.
In 3 large prospective cohorts with up to 32 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of CVD. These findings support the recommendations of the 2015-2020 Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.
Plasma branched-chain amino acids (BCAAs, including leucine, isoleucine and valine) were recently related to risk of type 2 diabetes (T2D). Dietary intake is the only source of BCAAs; however, little ...is known about whether habitual dietary intake of BCAAs affects risk of T2D.
We assessed associations between cumulative consumption of BCAAs and risk of T2D among participants from three prospective cohorts: the Nurses' Health Study (NHS; followed from 1980 to 2012); NHS II (followed from 1991 to 2011); and the Health Professionals Follow-up Study (HPFS; followed from 1986 to 2010).
We documented 16 097 incident T2D events during up to 32 years of follow-up. After adjustment for demographics and traditional risk factors, higher total BCAA intake was associated with an increased risk of T2D in men and women. In the meta-analysis of all cohorts, comparing participants in the highest quintile with those in the lowest quintile of intake, hazard ratios (95%confidence intervals) were for leucine 1.13 (1.07-1.19), for isoleucine 1.13 (1.07-1.19) and for valine 1.11 (1.05-1.17) (all P for trend < 0.001). In a healthy subsample, higher dietary BCAAs were significantly associated with higher plasma levels of these amino acids (P for trend = 0.01).
Our data suggest that high consumption of BCAAs is associated with an increased risk of T2D.
Animal studies suggest vital roles of sphingolipids, especially ceramides, in the pathogenesis of type 2 diabetes (T2D) via pathways involved in insulin resistance, β-cell dysfunction, and ...inflammation, but human studies are limited. We aimed to evaluate the associations of circulating sphingolipids with incident T2D and to explore underlying mechanisms.
The current study included 826 men and 1,148 women who were aged 50-70 years, from Beijing and Shanghai, and without T2D in 2005 and who were resurveyed in 2011. Cardiometabolic traits were measured at baseline and follow-up surveys. A total of 76 sphingolipids were quantified using high-coverage targeted lipidomics. Summary data for 2-sample Mendelian randomization were obtained from genome-wide association studies of circulating sphingolipids and the China Health and Nutrition Survey (n = 5,731). During the 6-year period, 529 participants developed T2D. Eleven novel and 3 reported sphingolipids, namely ceramides (d18:1/18:1, d18:1/20:0, d18:1/20:1, d18:1/22:1), saturated sphingomyelins (C34:0, C36:0, C38:0, C40:0), unsaturated sphingomyelins (C34:1, C36:1, C42:3), hydroxyl-sphingomyelins (C34:1, C38:3), and a hexosylceramide (d18:1/20:1), were positively associated with incident T2D (relative risks RRs: 1.14-1.21; all P < 0.001), after multivariate adjustment including lifestyle characteristics and BMI. Network analysis further identified 5 modules, and 2 modules containing saturated sphingomyelins showed the strongest associations with increased T2D risk (RRQ4 versus Q1 = 1.59 and 1.43; both Ptrend < 0.001). Mediation analysis suggested that the detrimental associations of 13 sphingolipids with T2D were largely mediated through β-cell dysfunction, as indicated by HOMA-B (mediation proportion: 11.19%-42.42%; all P < 0.001). Moreover, Mendelian randomization evidenced a positive association between a genetically instrumented ceramide (d18:1/20:1) and T2D (odds ratio: 1.15 95% CI 1.05-1.26; P = 0.002). Main limitations in the current study included potential undiagnosed cases and lack of an independent population for replication.
In this study, we observed that a panel of novel sphingolipids with unique structures were positively associated with incident T2D, largely mediated through β-cell dysfunction, in Chinese individuals.
The current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term ...risk of total and cause-specific mortality.
To examine the associations of dietary scores for 4 healthy eating patterns with risk of total and cause-specific mortality.
This prospective cohort study included initially healthy women from the Nurses' Health Study (NHS; 1984-2020) and men from the Health Professionals Follow-up Study (HPFS; 1986-2020).
Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED) score, Healthful Plant-based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI).
The main outcomes were total and cause-specific mortality overall and stratified by race and ethnicity and other potential risk factors.
The final study sample included 75 230 women from the NHS (mean SD baseline age, 50.2 7.2 years) and 44 085 men from the HPFS (mean SD baseline age, 53.3 9.6 years). During a total of 3 559 056 person-years of follow-up, 31 263 women and 22 900 men died. When comparing the highest with the lowest quintiles, the pooled multivariable-adjusted HRs of total mortality were 0.81 (95% CI, 0.79-0.84) for HEI-2015, 0.82 (95% CI, 0.79-0.84) for AMED score, 0.86 (95% CI, 0.83-0.89) for HPDI, and 0.80 (95% CI, 0.77-0.82) for AHEI (P < .001 for trend for all). All dietary scores were significantly inversely associated with death from cardiovascular disease, cancer, and respiratory disease. The AMED score and AHEI were inversely associated with mortality from neurodegenerative disease. The inverse associations between these scores and risk of mortality were consistent in different racial and ethnic groups, including Hispanic, non-Hispanic Black, and non-Hispanic White individuals.
In this cohort study of 2 large prospective cohorts with up to 36 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of total and cause-specific mortality. These findings support the recommendations of Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.
Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in ...response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902.
Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of ...the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment.
Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA.
Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.
Polygenic risk scores (PRSs) are weighted sums of risk allele counts of single-nucleotide polymorphisms (SNPs) associated with a disease or trait. PRSs are typically constructed based on published ...results from Genome-Wide Association Studies (GWASs), and the majority of which has been performed in large populations of European ancestry (EA) individuals. Although many genotype-trait associations have generalized across populations, the optimal choice of SNPs and weights for PRSs may differ between populations due to different linkage disequilibrium (LD) and allele frequency patterns. We compare various approaches for PRS construction, using GWAS results from both large EA studies and a smaller study in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL,
). We consider multiple approaches for selecting SNPs and for computing SNP weights. We study the performance of the resulting PRSs in an independent study of Hispanics/Latinos from the Women's Health Initiative (WHI,
). We support our investigation with simulation studies of potential genetic architectures in a single locus. We observed that selecting variants based on EA GWASs generally performs well, except for blood pressure trait. However, the use of EA GWASs for weight estimation was suboptimal. Using non-EA GWAS results to estimate weights improved results.
Genome-wide association studies have identified loci associated with coronary heart disease in whites of European ancestry. This study evaluated whether genetic markers previously identified in ...whites are associated with nonfatal acute myocardial infarction (MI) in Hispanics.
Cases (n=1989) with a first nonfatal acute MI and population-based controls (n=2096) living in Costa Rica were studied. Fourteen single-nucleotide polymorphisms were genotyped. Seven single-nucleotide polymorphisms at 3 independent loci showed significant associations with MI. The odds ratios for the loci with the strongest associations were 1.16 (95 confidence interval CI, 1.05 to 1.27) for rs4977574 (CDKN2A/2B), 1.15 (95 CI, 1.03 to 1.29) for rs646776 (CELSR2-PSRC1-SORT1), and 1.22 (95 CI, 1.08 to 1.38) for rs501120 (CXCL12); the corresponding PARs were 6.8, 10.5, and 15.2; respectively. We developed a genetic risk score by summing the number of the top 3 associated risk alleles. The OR for MI per genetic risk score unit was 1.18 (95 CI, 1.11 to 1.25; P=4.83 × 10(-8)). Discrimination of MI was significantly improved (P=0.02) when the genetic risk score was added to a model including clinical predictors. However, the increase in the area under the receiver-operating characteristic curve after the genetic risk score was added was moderate, from 0.67 (95 CI, 0.65 to 0.69) to 0.68 (95 CI, 0.66 to 0.70).
These results indicate both the consistency and disparity of genetic effects on risk of MI between Hispanic and white populations. The improvement in the identified genetic markers on discrimination of MI in Hispanics was modest.
Genome-wide association studies (GWASs) have increased our knowledge of loci associated with a range of human diseases. However, applying such findings to elucidate pathophysiology and promote drug ...discovery remains challenging. Here, we created isogenic human ESCs (hESCs) with mutations in GWAS-identified susceptibility genes for type 2 diabetes. In pancreatic beta-like cells differentiated from these lines, we found that mutations in CDKAL1, KCNQ1, and KCNJ11 led to impaired glucose secretion in vitro and in vivo, coinciding with defective glucose homeostasis. CDKAL1 mutant insulin+ cells were also hypersensitive to glucolipotoxicity. A high-content chemical screen identified a candidate drug that rescued CDKAL1-specific defects in vitro and in vivo by inhibiting the FOS/JUN pathway. Our approach of a proof-of-principle platform, which uses isogenic hESCs for functional evaluation of GWAS-identified loci and identification of a drug candidate that rescues gene-specific defects, paves the way for precision therapy of metabolic diseases.
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•An isogenic hESC-based platform defines the precise roles of T2DM-associated genes•CDKAL1−/−, KCNJ11−/−, and KCNQ1−/− beta-like cells show defective insulin secretion•CDKAL1−/− beta-like cells are hypersensitive to glucotoxicity and lipotoxicity•T5224 rescues CDKAL1−/−-induced beta cell defects by inhibiting the FOS/JUN pathway
Zeng et al. report functional evaluation of GWAS-identified candidate diabetes genes in an isogenic hESC-based platform. The authors find that biallelic mutations in CDKAL1, KCNQ1, and KCNJ11 caused impaired insulin secretion both in vitro and in vivo and identified the compound T5224, which rescued mutant CDKAL1-associated pancreatic beta cell defects by inhibiting the FOS/JUN pathway.
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