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Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study.

ABSTRACT: The aim of this study was to examine the associations between 16 specific single nucleotide polymorphisms (SNPs) in 8 obesity-related genes and overall and cause-specific mortality. We also examined the associations between the SNPs and body mass index (BMI) and change in BMI over time.Data were analyzed from 9,919 individuals who participated in two large community-based cohort studies conducted in Washington County, Maryland in 1974 (CLUE I) and 1989 (CLUE II). DNA from blood collected in 1989 was genotyped for 16 SNPs in 8 obesity-related genes: monoamine oxidase A (MAOA), lipoprotein lipase (LPL), paraoxonase 1 and 2 (PON1 and PON2), leptin receptor (LEPR), tumor necrosis factor-alpha (TNFalpha), and peroxisome proliferative activated receptor-gamma and -delta (PPARG and PPARD). Data on height and weight in 1989 (CLUE II baseline) and at age 21 were collected from participants at the time of blood collection. All participants were followed from 1989 to the date of death or the end of follow-up in 2005. Cox proportional hazards regression was used to obtain the relative risk (RR) estimates and 95% confidence intervals (CI) for each SNP and mortality outcomes.The results showed no patterns of association for the selected SNPs and the all-cause and cause-specific mortality outcomes, although statistically significant associations (p < 0.05) were observed between PPARG rs4684847 and all-cause mortality (CC: reference; CT: RR 0.99, 95% CI 0.89, 1.11; TT: RR 0.60, 95% CI 0.39, 0.93) and cancer-related mortality (CC: reference; CT: RR 1.01, 95% CI 0.82, 1.25; TT: RR 0.22, 95% CI 0.06, 0.90) and TNFalpha rs1799964 and cancer-related mortality (TT: reference; CT: RR 1.23, 95% CI 1.03, 1.47; CC: RR 0.83, 95% CI 0.54, 1.28). Additional analyses showed significant associations between SNPs in LEPR with BMI (rs1137101) and change in BMI over time (rs1045895 and rs1137101).Findings from this cohort study suggest that the selected SNPs are not associated with overall or cause-specific death, although several LEPR SNPs may be related to BMI and BMI change over time.

SUBMITTER: Gallicchio L

PROVIDER: S-EPMC2763854 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study.

Gallicchio Lisa L Chang Howard H HH Christo Dana K DK Thuita Lucy L Huang Han Yao HY Strickland Paul P Ruczinski Ingo I Clipp Sandra S Helzlsouer Kathy J KJ

BMC medical genetics 20091009

<h4>Background</h4>The aim of this study was to examine the associations between 16 specific single nucleotide polymorphisms (SNPs) in 8 obesity-related genes and overall and cause-specific mortality. We also examined the associations between the SNPs and body mass index (BMI) and change in BMI over time.<h4>Methods</h4>Data were analyzed from 9,919 individuals who participated in two large community-based cohort studies conducted in Washington County, Maryland in 1974 (CLUE I) and 1989 (CLUE II ...[more]

PMID: 19818126

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Project description:BackgroundPrevious data on the association between central obesity and mortality are controversial. The aim of this study was to determine the associations between central obesity, as measured by the waist-to-height ratio (WtHR) and waist circumference (WC), with all cause and cause-specific mortality in U.S. adults.MethodsThe study subjects comprised a nationally representative sample of 33,569 adults >20 years of age who were recruited in the National Health and Nutrition Examination Survey between 1999 and 2014. Anthropometric data, including weight, height, and WC, were measured at each of the eight waves using consistent methodology. Death and underlying causes of death were ascertained through 31 December 2015. The association between central obesity and mortality were determined using weighted Cox proportional hazards regression models.ResultsA total of 4013 deaths occurred during a median follow-up of 7.33 years (263,029 person-years). Compared with the subjects in WtHR tertile 1, the subjects in tertiles 2 and 3 were at a higher risk of mortality from all-cause (tertile 2-hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.13-1.47; tertile 3-HR: 1.96; 95% CI: 1.64-2.34) and cardiovascular diseases [CVDs] (tertile 2-HR: 1.40; 95% CI: 1.09-1.79; tertile 3-HR: 2.00; 95% CI: 1.47-2.73). Similarly, compared with the subjects in WC tertile 1, the subjects in tertiles 2 and 3 were at a higher risk of mortality from all-cause (tertile 2-HR: 1.15; 95% CI: 1.00-1.31; tertile 3-HR: 1.39; 95% CI: 1.15-1.67) and CVD (tertile 2-HR: 1.48; 95% CI: 1.14-1.93; tertile 3-HR: 1.74; 95% CI: 1.26-2.42). Restricted cubic spline analyses revealed an S-shaped and linear dose-relationship between WtHR and WC with all-cause mortality. Moreover, a WtHR> 0.58 or a WC > 0.98m was shown to be a risk factor for all-cause mortality.ConclusionsCentral obesity was significantly associated with increased risk of all-cause and CVD-related mortality, especially heart diseases-related mortality, even among normal weight adults. In addition to weight control, guideline designer should provide recommendations for people to decrease abdominal fat accumulation, in their effort to reduce mortality risk in later life.

Project description:BACKGROUND:Pediatric obesity is associated with increased risk of premature death from middle age onward, but whether the risk is already increased in young adulthood is unclear. The aim was to investigate whether individuals who had obesity in childhood have an increased mortality risk in young adulthood, compared with a population-based comparison group. METHODS AND FINDINGS:In this prospective cohort study, we linked nationwide registers and collected data on 41,359 individuals. Individuals enrolled at age 3-17.9 years in the Swedish Childhood Obesity Treatment Register (BORIS) and living in Sweden on their 18th birthday (start of follow-up) were included. A comparison group was matched by year of birth, sex, and area of residence. We analyzed all-cause mortality and cause-specific mortality using Cox proportional hazards models, adjusted according to group, sex, Nordic origin, and parental socioeconomic status (SES). Over 190,752 person-years of follow-up (median follow-up time 3.6 years), 104 deaths were recorded. Median (IQR) age at death was 22.0 (20.0-24.5) years. In the childhood obesity cohort, 0.55% (n = 39) died during the follow-up period, compared to 0.19% (n = 65) in the comparison group (p < 0.001). More than a quarter of the deaths among individuals in the childhood obesity cohort had obesity recorded as a primary or contributing cause of death. Male sex and low parental SES were associated with premature all-cause mortality. Suicide and self-harm with undetermined intent were the main cause of death in both groups. The largest difference between the groups lay within endogenous causes of death, where children who had undergone obesity treatment had an adjusted mortality rate ratio of 4.04 (95% CI 2.00-8.17, p < 0.001) compared with the comparison group. The main study limitation was the lack of anthropometric data in the comparison group. CONCLUSIONS:Our study shows that the risk of mortality in early adulthood may be higher for individuals who had obesity in childhood compared to a population-based comparison group.

Project description:ObjectiveTo investigate the association of spontaneous abortion with the risk of all cause and cause specific premature mortality (death before the age of 70).DesignProspective cohort study.SettingThe Nurses' Health Study II (1993-2017), United States.Participants101 681 ever gravid female nurses participating in the Nurses' Health Study II.Main outcomes measuresLifetime occurrence of spontaneous abortion in pregnancies lasting less than 6 months, determined by biennial questionnaires. Hazard ratios and 95% confidence intervals for all cause and cause specific premature death according to the occurrence of spontaneous abortion, estimated with time dependent Cox proportional hazards models.ResultsDuring 24 years of follow-up, 2936 premature deaths were recorded, including 1346 deaths from cancer and 269 from cardiovascular disease. Crude all cause mortality rates were comparable for women with and without a history of spontaneous abortion (1.24 per 1000 person years in both groups) but were higher for women experiencing three or more spontaneous abortions (1.47 per 1000 person years) and for women reporting their first spontaneous abortion before the age of 24 (1.69 per 1000 person years). The corresponding age adjusted hazard ratios for all cause premature death during follow-up were 1.02 (95% confidence interval 0.94 to 1.11), 1.39 (1.03 to 1.86), and 1.27 (1.11 to 1.46), respectively. After adjusting for confounding factors and updated dietary and lifestyle factors, the occurrence of spontaneous abortion was associated with a hazard ratio of 1.19 (95% confidence interval 1.08 to 1.30) for premature mortality during follow-up. The association was stronger for recurrent spontaneous abortions (hazard ratio 1.59, 95% confidence interval 1.17 to 2.15 for three or more spontaneous abortions; 1.23, 1.00 to 1.50 for two; and 1.16, 1.05 to 1.28 for one compared with none), and for spontaneous abortions occurring early in a woman's reproductive life (1.32, 1.14 to 1.53 for age ≤23; 1.16, 1.01 to 1.33 for ages 24-29; and 1.12, 0.98 to 1.28 for age ≥30 compared with none). When cause specific mortality was evaluated, the association of spontaneous abortion with premature death was strongest for deaths from cardiovascular disease (1.48, 1.09 to 1.99). Spontaneous abortion was not related to premature death from cancer (1.08, 0.94 to 1.24).ConclusionsSpontaneous abortion was associated with an increased risk of premature mortality, particularly death from cardiovascular disease.

Project description:OBJECTIVE:To determine the association between recommended physical activity according to the 2018 physical activity guidelines for Americans and all cause and cause specific mortality using a nationally representative sample of US adults. DESIGN:Population based cohort study. SETTING:National Health Interview Survey (1997-2014) with linkage to the National Death Index records to 31 December 2015. PARTICIPANTS:479 856 adults aged 18 years or older. EXPOSURES:Participant self-reports of the amount of leisure time spent in aerobic physical activity and muscle strengthening activity each week were combined and categorised into four groups: insufficient activity, aerobic activity only, muscle strengthening only, and both aerobic and muscle strengthening activities according to the physical activity guidelines. MAIN OUTCOME MEASURES:All cause mortality and cause specific mortality (cardiovascular disease, cancer, chronic lower respiratory tract diseases, accidents and injuries, Alzheimer's disease, diabetes mellitus, influenza and pneumonia, and nephritis, nephrotic syndrome, or nephrosis) obtained from the National Death Index records. RESULTS:During a median follow-up of 8.75 years, 59 819 adults died from all causes, 13 509 from cardiovascular disease, 14 375 from cancer, 3188 from chronic lower respiratory tract diseases, 2477 from accidents and injuries, 1470 from Alzheimer's disease, 1803 from diabetes mellitus, 1135 from influenza and pneumonia, and 1129 from nephritis, nephrotic syndrome, or nephrosis. Compared with those who did not meet the physical activity guidelines (n=268 193), those who engaged in recommended muscle strengthening activity (n=21 428; hazard ratio 0.89, 95% confidence interval 0.85 to 0.94) or aerobic activity (n=113 851; 0.71, 0.69 to 0.72) were found to be at reduced risk of all cause mortality; and even larger survival benefits were found in those engaged in both activities (n=76 384; 0.60, 0.57 to 0.62). In addition, similar patterns were reported for cause specific mortality from cardiovascular disease, cancer, and chronic lower respiratory tract diseases. CONCLUSIONS:Adults who engage in leisure time aerobic and muscle strengthening activities at levels recommended by the 2018 physical activity guidelines for Americans show greatly reduced risk of all cause and cause specific mortality. These data suggest that the physical activity levels recommended in the guidelines are associated with important survival benefits.

Project description:Background Dietary recommendations regarding protein intake have been focused on the amount of protein. However, such recommendations without considering specific protein sources may be simplistic and insufficient. Methods and Results We included 102 521 postmenopausal women enrolled in the Women's Health Initiative between 1993 and 1998, and followed them through February 2017. During 1 876 205 person-years of follow-up, 25 976 deaths occurred. Comparing the highest with the lowest quintile, plant protein intake was inversely associated with all-cause mortality (hazard ratio [HR], 0.91 [0.86, 0.96]), cardiovascular disease mortality (HR, 0.88 [0.79, 0.97]), and dementia mortality (HR, 0.79 [0.67, 0.94]). Among major protein sources, comparing the highest with the lowest quintile of consumption, processed red meat (HR, 1.06 [1.01, 1.10]) or eggs (HR, 1.14 [1.10, 1.19]) was associated with higher risk of all-cause mortality. Unprocessed red meat (HR, 1.12 [1.02, 1.23]), eggs (HR, 1.24 [1.14, 1.34]), or dairy products (HR, 1.11 [1.02, 1.22]) was associated with higher risk of cardiovascular disease mortality. Egg consumption was associated with higher risk of cancer mortality (HR, 1.10 [1.02, 1.19]). Processed red meat consumption was associated with higher risk of dementia mortality (HR, 1.20 [1.05, 1.32]), while consumption of poultry (HR, 0.85 [0.75, 0.97]) or eggs (HR, 0.86 [0.75, 0.98]) was associated with lower risk of dementia mortality. In substitution analysis, substituting of animal protein with plant protein was associated with a lower risk of all-cause mortality, cardiovascular disease mortality, and dementia mortality, and substitution of total red meat, eggs, or dairy products with nuts was associated with a lower risk of all-cause mortality. Conclusions Different dietary protein sources have varying associations with all-cause mortality, cardiovascular disease mortality, and dementia mortality. Our findings support the need for consideration of protein sources in future dietary guidelines.

Project description:ObjectiveTo investigate the association between weight changes across adulthood and mortality.DesignProspective cohort study.SettingUS National Health and Nutrition Examination Survey (NHANES) 1988-94 and 1999-2014.Participants36 051 people aged 40 years or over with measured body weight and height at baseline and recalled weight at young adulthood (25 years old) and middle adulthood (10 years before baseline).Main outcome measuresAll cause and cause specific mortality from baseline until 31 December 2015.ResultsDuring a mean follow-up of 12.3 years, 10 500 deaths occurred. Compared with participants who remained at normal weight, those moving from the non-obese to obese category between young and middle adulthood had a 22% (hazard ratio 1.22, 95% confidence interval 1.11 to 1.33) and 49% (1.49, 1.21 to 1.83) higher risk of all cause mortality and heart disease mortality, respectively. Changing from obese to non-obese body mass index over this period was not significantly associated with mortality risk. An obese to non-obese weight change pattern from middle to late adulthood was associated with increased risk of all cause mortality (1.30, 1.16 to 1.45) and heart disease mortality (1.48, 1.14 to 1.92), whereas moving from the non-obese to obese category over this period was not significantly associated with mortality risk. Maintaining obesity across adulthood was consistently associated with increased risk of all cause mortality; the hazard ratio was 1.72 (1.52 to 1.95) from young to middle adulthood, 1.61 (1.41 to 1.84) from young to late adulthood, and 1.20 (1.09 to 1.32) from middle to late adulthood. Maximum overweight had a very modest or null association with mortality across adulthood. No significant associations were found between various weight change patterns and cancer mortality.ConclusionsStable obesity across adulthood, weight gain from young to middle adulthood, and weight loss from middle to late adulthood were associated with increased risks of mortality. The findings imply that maintaining normal weight across adulthood, especially preventing weight gain in early adulthood, is important for preventing premature deaths in later life.

Dataset Information

Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study.

Publications

Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study.

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