The effect of GWAS identified BMI loci on changes in body weight among middle‐aged danes during a five‐year period

Sandholt, Camilla H.; Allin, Kristine H.; Toft, Ulla; Borglykke, Anders; Ribel‐Madsen, Rasmus; Sparsø, Thomas; Justesen, Johanne Marie; Harder, Marie Neergaard; Jørgensen, Torben; Hansen, Torben; Pedersen, Oluf

doi:10.1002/oby.20540

Cited by 29 publications

(26 citation statements)

References 25 publications

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“…We found strong evidence to support the association between weight gain in adults and postmenopausal breast cancer, but weight gain is probably linked to environmental factors that are not captured by genetic risk factors. 96 Moreover, some evidence exists that these associations may differ according to oestrogen and progesterone receptor status of the tumour (supplementary tables 6 and 7), 68 97 but large investigations in this area are lacking.…”

Section: Comparison With Other Studiesmentioning

confidence: 99%

Adiposity and cancer at major anatomical sites: umbrella review of the literature

Kyrgiou

Kalliala

Markozannes

et al. 2017

BMJ

630

473

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Objective To evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer. Design Umbrella review of systematic reviews and meta-analyses. Data sources PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references. Eligibility criteria Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer. Data synthesis Primary analysis focused on cohort studies exploring associations for continuous measures of adiposity. The evidence was graded into strong, highly suggestive, suggestive, or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Results 204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m2 increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality. Conclusions Although the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming...

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Section: Comparison With Other Studiesmentioning

confidence: 99%

Adiposity and cancer at major anatomical sites: umbrella review of the literature

Kyrgiou

Kalliala

Markozannes

et al. 2017

BMJ

630

473

View full text Add to dashboard Cite

show abstract

“…We used a genetically determined higher BMI to investigate and quantify the effect of adiposity on asthma, hay fever, biomarkers of allergy (IgE antibodies) and lung function in adults (≥16 years) according to the principles of Mendelian randomization. We included 26 SNPs, including the FTO rs9939609, that are associated with BMI at genomewide significance levels in a number of genomewide association studies (GWAS) previously validated in one of the included studies …”

Section: Introductionmentioning

confidence: 99%

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

Skaaby

Taylor

Thuesen

et al. 2017

Allergy

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“…Individuals participating in a study such as Inter99 may be a distinctive group of individuals with a higher awareness of their health (41). Moreover, individuals who participated in the follow-up examination after 5 years had a lower body weight and overall a healthier lifestyle at baseline compared with nonattendees (42). Therefore we cannot conclude that the results of the present study are directly transferrable to the general population as a whole.…”

Section: Interactionsmentioning

confidence: 77%

Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during 5 years

Justesen

Andersson

Allin

et al. 2016

Journal of Lipid Research

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A high level of circulating triglycerides is a risk factor for type 2 diabetes, myocardial infarction, ischemic heart disease, and all-cause mortality (1-4). A recent Mendelian randomization study supports a causal effect of triglycerides on coronary heart disease risk (5). Regulation of blood levels of triglycerides involves a complex interplay implicating both the liver and pancreas. Some of the important players in this regard are body adiposity, insulin resistance, and glucose homeostasis (6). In addition, circulating triglyceride levels are heritable, as shown in a recent population-based study of twins (H 2 = 0.59; h 2 = 0.33) (7). Genetic association studies have identified more than 40 SNPs Abstract Blood concentrations of triglycerides are influenced by genetic factors as well as a number of environmental factors, including adiposity and glucose homeostasis. The aim was to investigate the association between a serum triglyceride weighted genetic risk score (wGRS) and changes in fasting serum triglyceride level over 5 years and to test whether the effect of the wGRS was modified by 5 year changes of adiposity, insulin resistance, and lifestyle factors. A total of 3,474 nondiabetic individuals from the Danish Inter99 cohort participated in both the baseline and 5 year follow-up physical examinations and had information on the wGRS comprising 39 genetic variants. In a linear regression model adjusted for age, sex, and baseline serum triglyceride, the wGRS was associated with increased serum triglyceride levels over 5 years [per allele effect = 1.3% (1.0-1.6%); P = 1.0 × 10 17 ]. This triglyceride-increasing effect of the wGRS interacted with changes in insulin resistance (P interaction = 1.5 × 10 6). This interaction indicated that the effect of the wGRS was stronger in individuals who became more insulin resistant over 5 years. In conclusion, our findings suggest that increased genetic risk load is associated with a larger

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The effect of GWAS identified BMI loci on changes in body weight among middle‐aged danes during a five‐year period

Cited by 29 publications

References 25 publications

Adiposity and cancer at major anatomical sites: umbrella review of the literature

Adiposity and cancer at major anatomical sites: umbrella review of the literature

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during 5 years

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