Mendelian randomization study of height and risk of colorectal cancer.
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ABSTRACT:
SUBMITTER: Thrift AP
PROVIDER: S-EPMC4481609 | biostudies-literature | 2015 Apr
REPOSITORIES: biostudies-literature
Publications
Mendelian randomization study of height and risk of colorectal cancer.
Thrift Aaron P AP Gong Jian J Peters Ulrike U Chang-Claude Jenny J Rudolph Anja A Slattery Martha L ML Chan Andrew T AT Esko Tonu T Wood Andrew R AR Yang Jian J Vedantam Sailaja S Gustafsson Stefan S Pers Tune H TH Baron John A JA Bezieau Stéphane S Küry Sébastien S Ogino Shuji S Berndt Sonja I SI Casey Graham G Haile Robert W RW Du Mengmeng M Harrison Tabitha A TA Thornquist Mark M Duggan David J DJ Le Marchand Loic L Lemire Mathieu M Lindor Noralane M NM Seminara Daniela D Song Mingyang M Thibodeau Stephen N SN Cotterchio Michelle M Win Aung Ko AK Jenkins Mark A MA Hopper John L JL Ulrich Cornelia M CM Potter John D JD Newcomb Polly A PA Schoen Robert E RE Hoffmeister Michael M Brenner Hermann H White Emily E Hsu Li L Campbell Peter T PT
International journal of epidemiology 20150401 2
<h4>Background</h4>For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk.<h4>Methods</h4>To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using ...[more]
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Project description:BackgroundHigh body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer.MethodsWe used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study-identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis.ResultsIndividuals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk [per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10-1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m(2), 1.50; 95% CI, 1.13-2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m(2), 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m(2), 1.18; 95% CI, 0.73-1.92).ConclusionsHigh BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation.ImpactOverall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer.
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Project description:BackgroundEpidemiological studies have provided evidence that there is an association between diet and colorectal cancer. However, the causal relationship between dietary habits and colorectal cancer remains unknown.MethodsThe UK Biobank provided summary-level genome-wide association study data for nine dietary habits, including alcohol consumption (n = 549,703), instant coffee consumption (n = 250,308), fruit consumption (n = 210,947), meat consumption (n = 210,947), full cream milk consumption (n = 41,306), sweets consumption (n = 25,521), tea consumption (n = 501,494), vegetable consumption (n = 210,947), and yogurt/ice cream consumption (n = 210,947). Additionally, data on colorectal cancer were collected, consisting of 5,567 cases and 372,016 controls. The MR analysis employed inverse variance weighted, weighted median, MR-Egger regression, and MR multivariate residuals tests.ResultsIn the predominantly European population, a positive association was observed between vegetables (OR = 1.014, 95% CI = 1.000-1.029, p = 0.048) and an increased risk of colorectal cancer. The results for vegetable did not survive correction for multiple comparisons. However, no strong evidence was found for other dietary factors, such as alcohol (OR = 1.012, 95% CI = 0.974-1.051, p = 0.556), fruit (OR = 1.007, 95% CI = 0.986-1.029, p = 0.512), meat (OR = 1.000, 95% CI = 0.987-1.026, p = 0.968), full cream milk (OR = 1.019, 95% CI = 0.979-1.061, p = 0.357), sweets (OR = 0.998, 95% CI = 0.991-1.004, p = 0.524), and tea (OR = 1.002, 95% CI = 0.994-1.009, p = 0.672), with regards to colorectal cancer risk in the European population.ConclusionsOur study highlights the need for a more nuanced approach to dietary recommendations for CRC prevention, with greater emphasis adherence to the Mediterranean dietary pattern.
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Project description:BackgroundObservational studies have identified height as a strong risk factor for atrial fibrillation, but this finding may be limited by residual confounding. We aimed to examine genetic variation in height within the Mendelian randomization (MR) framework to determine whether height has a causal effect on risk of atrial fibrillation.Methods and findingsIn summary-level analyses, MR was performed using summary statistics from genome-wide association studies of height (GIANT/UK Biobank; 693,529 individuals) and atrial fibrillation (AFGen; 65,446 cases and 522,744 controls), finding that each 1-SD increase in genetically predicted height increased the odds of atrial fibrillation (odds ratio [OR] 1.34; 95% CI 1.29 to 1.40; p = 5 × 10-42). This result remained consistent in sensitivity analyses with MR methods that make different assumptions about the presence of pleiotropy, and when accounting for the effects of traditional cardiovascular risk factors on atrial fibrillation. Individual-level phenome-wide association studies of height and a height genetic risk score were performed among 6,567 European-ancestry participants of the Penn Medicine Biobank (median age at enrollment 63 years, interquartile range 55-72; 38% female; recruitment 2008-2015), confirming prior observational associations between height and atrial fibrillation. Individual-level MR confirmed that each 1-SD increase in height increased the odds of atrial fibrillation, including adjustment for clinical and echocardiographic confounders (OR 1.89; 95% CI 1.50 to 2.40; p = 0.007). The main limitations of this study include potential bias from pleiotropic effects of genetic variants, and lack of generalizability of individual-level findings to non-European populations.ConclusionsIn this study, we observed evidence that height is likely a positive causal risk factor for atrial fibrillation. Further study is needed to determine whether risk prediction tools including height or anthropometric risk factors can be used to improve screening and primary prevention of atrial fibrillation, and whether biological pathways involved in height may offer new targets for treatment of atrial fibrillation.
| S-EPMC7544133 | biostudies-literature
Project description:BackgroundTaller people have a lower risk of coronary heart disease but a higher risk of many cancers. Mendelian randomization (MR) studies in unrelated individuals (population MR) have suggested that these relationships are potentially causal. However, population MR studies are sensitive to demography (population stratification, assortative mating) and familial (indirect genetic) effects.MethodsIn this study, we performed within-sibship MR analyses using 78,988 siblings, a design robust against demography and indirect genetic effects of parents. For comparison, we also applied population MR and estimated associations with measured height.ResultsWithin-sibship MR estimated that 1 SD taller height lowers the odds of coronary heart disease by 14% (95% CI: 3-23%) but increases the odds of cancer by 18% (95% CI: 3-34%), highly consistent with population MR and height-disease association estimates. There was some evidence that taller height reduces systolic blood pressure and low-density lipoprotein cholesterol, which may mediate some of the protective effects of taller height on coronary heart disease risk.ConclusionsFor the first time, we have demonstrated that the purported effects of height on adulthood disease risk are unlikely to be explained by demographic or familial factors, and so likely reflect an individual-level causal effect. Disentangling the mechanisms via which height affects disease risk may improve the understanding of the etiologies of atherosclerosis and carcinogenesis.FundingThis project was conducted by researchers at the MRC Integrative Epidemiology Unit (MC_UU_00011/1) and also supported by a Norwegian Research Council Grant number 295989.
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