scholarly journals Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254649
Author(s):  
Sehoon Park ◽  
Soojin Lee ◽  
Yaerim Kim ◽  
Yeonhee Lee ◽  
Min Woo Kang ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Kidney Function ◽  
Body Mass ◽  
Standard Error ◽  
Adult Height ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Observational Analysis

As adult height is linked to various health outcomes, further investigation of its causal effects on kidney function later in life is warranted. This study involved a cross-sectional observational analysis and summary-level Mendelian randomization (MR) analysis. First, the observational association between height and estimated GFR determined by creatinine (eGFRcreatinine) or cystatin C (eGFRcystatinC) was investigated in 467,182 individuals aged 40–69 using UK Biobank. Second, the genetic instrument for adult height, as reported by the GIANT consortium, was implemented, and summary-level MR of eGFRcreatinine and CKDcreatinine in a CKDGen genome-wide association study was performed (N = 567,460), with multivariable MR being adjusted for the effects of genetic predisposition on body mass index. To replicate the findings, additional two-sample MR using the summary statistics of eGFRcystatinC and CKDcystatinC in UK Biobank was performed (N = 321,405). In observational analysis, adult height was inversely associated with both eGFRcreatinine (per 1 SD, adjusted beta -1.039, standard error 0.129, P < 0.001) and eGFRcystatinC (adjusted beta -1.769, standard error 0.161, P < 0.001) in a multivariable model adjusted for clinicodemographic, anthropometric, metabolic, and social factors. Moreover, multivariable summary-level MR showed that a taller genetically predicted adult height was causally linked to a lower log-eGFRcreatinine (adjusted beta -0.007, standard error 0.001, P < 0.001) and a higher risk of CKDcreatinine (adjusted beta 0.083, standard error 0.019, P < 0.001). Other pleiotropy-robust sensitivity MR analysis results supported the findings. In addition, similar results were obtained by two-sample MR of eGFRcystatinC (adjusted beta -1.303, standard error 0.140, P < 0.001) and CKDcystatinC (adjusted beta 0.153, standard error 0.025, P < 0.001) in UK Biobank. In conclusion, the results of this study suggest that a taller adult height is causally linked to worse kidney function in middle-aged to elderly individuals, independent of the effect of body mass index.

scholarly journals Body mass index and mortality in UK Biobank: revised estimates using Mendelian randomization

2018 ◽  
Author(s):  
Kaitlin H Wade ◽  
David Carslake ◽  
Naveed Sattar ◽  
George Davey Smith ◽  
Nicholas J Timpson
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Genotypic Variation ◽  
Lung Cancer Mortality ◽  
Causal Role ◽  
Uk Biobank ◽  
All Cause Mortality

AbstractObjectiveObtain estimates of the causal relationship between different levels of body mass index (BMI) and mortality.MethodsMendelian randomization (MR) was conducted using genotypic variation reliably associated with BMI to test the causal effect of increasing BMI on all-cause and cause-specific mortality in participants of White British ancestry in UK Biobank.ResultsMR analyses supported existing evidence for a causal association between higher levels of BMI and greater risk of all-cause mortality (hazard ratio (HR) per 1kg/m2: 1.02; 95% CI: 0.97,1.06) and mortality from cardiovascular diseases (HR: 1.12; 95% CI: 1.02, 1.23), specifically coronary heart disease (HR: 1.19; 95% CI: 1.05, 1.35) and those other than stroke/aortic aneurysm (HR: 1.13; 95% CI: 0.93, 1.38), stomach cancer (HR: 1.30; 95% CI: 0.91, 1.86) and oesophageal cancer (HR: 1.08; 95% CI: 0.84, 1.38), and with decreased risk of lung cancer mortality (HR: 0.97; 95% CI: 0.84, 1.11). Sex-stratified analyses supported a causal role of higher BMI in increasing the risk of mortality from bladder cancer in males and other causes in females, but in decreasing the risk of respiratory disease mortality in males. The characteristic J-shaped observational association between BMI and mortality was visible with MR analyses but with a smaller value of BMI at which mortality risk was lowest and apparently flatter over a larger range of BMI.ConclusionResults support a causal role of higher BMI in increasing the risk of all-cause mortality and mortality from other causes. However, studies with greater numbers of deaths are needed to confirm the current findings.

scholarly journals Homogeneity in the association of body mass index with type 2 diabetes across the UK Biobank: A Mendelian randomization study

PLoS Medicine ◽  
2019 ◽  
Vol 16 (12) ◽  
pp. e1002982 ◽  
Author(s):  
Michael Wainberg ◽  
Anubha Mahajan ◽  
Anshul Kundaje ◽  
Mark I. McCarthy ◽  
Erik Ingelsson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
The Uk

scholarly journals Body mass index and height and risk of cutaneous melanoma: Mendelian randomization analyses

2020 ◽  
Vol 49 (4) ◽  
pp. 1236-1245 ◽  
Author(s):  
Jean Claude Dusingize ◽  
Catherine M Olsen ◽  
Jiyuan An ◽  
Nirmala Pandeya ◽  
Matthew H Law ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Positive Association ◽  
Sensitivity Analyses ◽  
Nucleotide Polymorphisms ◽  
Melanoma Risk ◽  
Lifestyle Risk Factors

Abstract Background Height and body mass index (BMI) have both been positively associated with melanoma risk, although findings for BMI have been less consistent than height. It remains unclear, however, whether these associations reflect causality or are due to residual confounding by environmental and lifestyle risk factors. We re-evaluated these associations using a two-sample Mendelian randomization (MR) approach. Methods We identified single nucleotide polymorphisms (SNPs) for BMI and height from separate genome-wide association study (GWAS) meta-analyses. We obtained melanoma SNPs from the most recent melanoma GWAS meta-analysis comprising 12 874 cases and 23 203 controls. We used the inverse variance-weighted estimator to derive separate causal risk estimates across all SNP instruments for BMI and height. Results Based on the combined estimate derived from 730 SNPs for BMI, we found no evidence of an association between genetically predicted BMI and melanoma [odds ratio (OR) per one standard deviation (1 SD) (4.6 kg/m2) increase in BMI 1.00, 95% confidence interval (CI): 0.91–1.11]. In contrast, we observed a positive association between genetically-predicted height (derived from a pooled estimate of 3290 SNPs) and melanoma risk [OR 1.08, 95% CI: 1.02–1.13, per 1 SD (9.27 cm) increase in height]. Sensitivity analyses using two alternative MR methods yielded similar results. Conclusions These findings provide no evidence for a causal association between higher BMI and melanoma, but support the notion that height is causally associated with melanoma risk. Mechanisms through which height influences melanoma risk remain unclear, and it remains possible that the effect could be mediated through diverse pathways including growth factors and even socioeconomic status.

scholarly journals Effects of body mass index on relationship status, social contact, and socioeconomic position: Mendelian Randomization study in UK Biobank

2019 ◽  
Author(s):  
Laura D Howe ◽  
Roshni Kanayalal ◽  
Robin N Beaumont ◽  
Alisha R Davies ◽  
Timothy M Frayling ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Relationship Status ◽  
Social Activities ◽  
Uk Biobank ◽  
Non Linear ◽  
Low Bmi ◽  
Degree Level ◽  
High Bmi

AbstractObjectiveTo assess whether body mass index (BMI) has a causal effect on social and socioeconomic factors, including whether both high and low BMI can be detrimental.DesignMendelian Randomization, using genetic variants for BMI to obtain unconfounded estimates, and non-linear Mendelian Randomization.SettingUK Biobank.Participants378,244 men and women of European ancestry, mean age 57 (SD 8 years).Main outcome measuresTownsend deprivation index, income, age completed full time education, degree level education, job class, employment status, cohabiting relationship status, participation in leisure and social activities, visits from friends and family, and having someone to confide in.ResultsHigher BMI was causally associated with higher deprivation, lower income, fewer years of education, lower odds of degree-level education and skilled employment. For example, a 1 SD higher genetically-determined BMI (4.8kg/m2 in UK Biobank) was associated with £1,660 less income per annum [95%CI: £950, £2,380]. Non-linear Mendelian Randomization provided evidence that both low BMI (bottom decile, <22kg/m2) and high BMI (top seven deciles, >24.6kg/m2) can increase deprivation and reduce income. In men only, higher BMI was related to lower participation in leisure and social activities. There was no evidence of causal effects of BMI on visits from friends and family or in having someone to confide in. Non-linear Mendelian Randomization analysis showed that low BMI (bottom three deciles, <23.5kg/m2) reduces the odds of cohabiting with a partner or spouse for men, whereas high BMI (top two deciles, >30.7kg/m2) reduces the odds of cohabitation with a partner or spouse for women.ConclusionsBMI affects social and socioeconomic outcomes, with both high and low BMI being detrimental for some measures of SEP. This suggests that in addition to health benefits, maintaining healthy ranges of BMI across the population could have benefits both for individuals and society.

scholarly journals Searching for the causal effects of body mass index in over 300 000 participants in UK Biobank, using Mendelian randomization

PLoS Genetics ◽  
2019 ◽  
Vol 15 (2) ◽  
pp. e1007951 ◽  
Author(s):  
Louise A. C. Millard ◽  
Neil M. Davies ◽  
Kate Tilling ◽  
Tom R. Gaunt ◽  
George Davey Smith
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Uk Biobank

scholarly journals Evidence of a common causal relationship between body mass index and inflammatory skin disease: a Mendelian Randomization study

2018 ◽  
Author(s):  
Ashley Budu-Aggrey ◽  
Ben Brumpton ◽  
Jess Tyrrell ◽  
Sarah Watkins ◽  
Ellen H Modalsli ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Causal Relationship ◽  
Body Mass ◽  
Skin Disease ◽  
Skin Diseases ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
Inflammatory Skin Disease ◽  
Level Data ◽  
Inflammatory Skin

ABSTRACTObjectivePsoriasis and eczema are common inflammatory skin diseases that have been reported to be associated with obesity. However, causality has not yet been established. We aimed to investigate the possible causal relationship between body mass index (BMI) and psoriasis or eczema.MethodsFollowing a review of published epidemiological evidence of the association between obesity and either psoriasis or eczema, Mendelian Randomization (MR) was used to test for a causal relationship between BMI and these inflammatory skin conditions. We used a genetic instrument comprising 97 single nucleotide polymorphisms (SNPs) associated with BMI. One-sample MR was conducted using individual-level data (401,508 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (731,021 individuals) from published BMI, psoriasis and eczema GWAS. The one-sample and two-sample MR estimates were meta-analysed using a fixed effect model. To explore the reverse causal direction, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis and eczema were used to test if inflammatory skin disease has a causal effect on BMI.ResultsPublished observational data show an association of greater BMI with both psoriasis and eczema case status. The observational associations were confirmed in UK Biobank and HUNT datasets. MR analyses provide evidence that higher BMI causally increases the odds of psoriasis (by 53% per 5 units higher BMI; OR= 1.09 (1.06 to 1.12) per 1 kg/m2; P=4.67×10-9) and eczema (by 8% per 5 units higher BMI; OR=1.02 (1.00 to 1.03) per 1 kg/m2; P=0.09). When investigating causality in the opposite direction, MR estimates provide little evidence for an effect of either psoriasis or eczema influencing BMI.ConclusionOur study, using genetic variants as instrumental variables for BMI, shows that higher BMI leads to a higher risk of inflammatory skin disease. The causal relationship was stronger for psoriasis than eczema. Therapies and life-style interventions aimed at controlling BMI or targeting the mechanisms linking obesity with skin inflammation may offer an opportunity for the prevention or treatment of these common skin diseases.

scholarly journals Association between smoking and body mass index among males aged 20 years and above: A study in rural Tamil Nadu, South India

2015 ◽  
Vol 4 (1) ◽  
pp. 53-58
Author(s):  
Anil C Mathew ◽  
Royce Kurian ◽  
KM Akshaya ◽  
S Karthikeyan ◽  
Thomas V Chacko
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Standard Error ◽  
Tamil Nadu ◽  
Smoking Status ◽  
Medical Science ◽  
Epidemiological Studies ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Quit Smoking

A large number of epidemiological studies reported an increase in mortality due to cancer and other diseases among lean individuals. In this paper we aimed to investigate the relationship between smoking status and Body Mass Index (BMI) in men aged 20 years and above. A cross sectional study was conducted in the rural field practice area of the Department of Community Medicine, PSG Institute of Medical Science and Research, Coimbatore during June and July 2010. A total of 459 men aged 20 years and above were included in the study. Statistical analyses were done using the General Linear Model procedure of SPSS. We observed that cigarette smokers weighed (Kg) less, p<0.01 (age adjusted mean ± standard error= 58.64±0.44) and were leaner, p<0.001 [age adjusted mean BMI (kg/m2) ± standard error=21.13±0.13] than ex/non-smokers (61.11±0.69 and 22.19± 0.2 respectively). Regarding the intensity of smoking and BMI, light smokers (1 to 20 cigarettes per day) were leaner than ex/non smokers (mean ± standard error were 21.13 ± 0.13, 22.19 ± 0.208 respectively, p< 0.001). Regarding the duration of smoking and BMI, a linear diminution in BMI is observed with increasing duration of cigarettes smoking compared to ex/non smokers (mean ± standard error of BMI) for ex/non smokers 22.19±0.208, 1 to 10 years of smoking 21.56 ± 0.221(p<0.05); 11 to 20 years of smoking 21.23±0.256 (p<0.01); 21 to 30 years of smoking 20.30 ± 0.333 (p<0.001); 30 and above years of smoking 20.07±0.501 (p<0.001). In conclusion, we found significant results confirming an association between cigarette smoking and lower BMI in men. Hence we recommended that health intervention programs to quit smoking should take into account the underlying perceived benefits of smoking with body weight.DOI: http://dx.doi.org/10.3329/seajph.v4i1.21841 South East Asia Journal of Public Health Vol.4(1) 2014: 53-58

scholarly journals Effects of body mass index on relationship status, social contact and socio-economic position: Mendelian randomization and within-sibling study in UK Biobank

2019 ◽  
Vol 49 (4) ◽  
pp. 1173-1184 ◽  
Author(s):  
Laura D Howe ◽  
Roshni Kanayalal ◽  
Sean Harrison ◽  
Robin N Beaumont ◽  
Alisha R Davies ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Specific Effect ◽  
Economic Outcomes ◽  
European Ancestry ◽  
Uk Biobank ◽  
Non Linear ◽  
Low Bmi ◽  
Economic Position

Abstract Background We assessed whether body mass index (BMI) affects social and socio-economic outcomes. Methods We used Mendelian randomization (MR), non-linear MR and non-genetic and MR within-sibling analyses, to estimate relationships of BMI with six socio-economic and four social outcomes in 378 244 people of European ancestry in UK Biobank. Results In MR of minimally related individuals, higher BMI was related to higher deprivation, lower income, fewer years of education, lower odds of degree-level education and skilled employment. Non-linear MR suggested both low (bottom decile, &lt;22 kg/m2) and high (top seven deciles, &gt;24.6 kg/m2) BMI, increased deprivation and reduced income. Non-genetic within-sibling analysis supported an effect of BMI on socio-economic position (SEP); precision in within-sibling MR was too low to draw inference about effects of BMI on SEP. There was some evidence of pleiotropy, with MR Egger suggesting limited effects of BMI on deprivation, although precision of these estimates is also low. Non-linear MR suggested that low BMI (bottom three deciles, &lt;23.5 kg/m2) reduces the odds of cohabiting with a partner or spouse in men, whereas high BMI (top two deciles, &gt;30.7 kg/m2) reduces the odds of cohabitation in women. Both non-genetic and MR within-sibling analyses supported this sex-specific effect of BMI on cohabitation. In men only, higher BMI was related to lower participation in leisure and social activities. There was little evidence that BMI affects visits from friends and family or having someone to confide in. Conclusions BMI may affect social and socio-economic outcomes, with both high and low BMI being detrimental for SEP, although larger within-family MR studies may help to test the robustness of MR results in unrelated individuals. Triangulation of evidence across MR and within-family analyses supports evidence of a sex-specific effect of BMI on cohabitation.

scholarly journals Age-varying genetic associations and implications for bias in Mendelian randomization analyses

2021 ◽  
Author(s):  
Jeremy A Labrecque ◽  
Sonja A Swanson
Keyword(s):  
Body Mass Index ◽  
Alcohol Consumption ◽  
Body Mass ◽  
Genetic Variants ◽  
Ldl Cholesterol ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
Genetic Associations ◽  
C Reactive Protein ◽  
Reactive Protein

Estimates from conventional Mendelian randomization (MR) analyses can be biased when the genetic variants proposed as instruments vary over age in their relationship with the exposure. For four exposures commonly studied using MR, we assessed the degree to which their relationship with genetic variants commonly used as instruments varies by age using flexible, spline-based models in UK Biobank data. Using these models, we then estimated how biased MR estimates would be due to age-varying relationships using plasmode simulations. We found that most genetic variants had age-varying relationships with the exposure for which they are a proposed instrument. Body mass index and LDL cholesterol had the most variation while alcohol consumption had very little. This variation over age led to small potential biases in some cases (e.g. alcohol consumption and C-reactive protein) and large potential biases for many proposed instruments for BMI and LDL.

Height, age at menarche, body weight and body mass index in life-long vegetarians

2005 ◽  
Vol 8 (7) ◽  
pp. 870-875 ◽  
Author(s):  
Magdalena Rosell ◽  
Paul Appleby ◽  
Tim Key
Keyword(s):  
Body Mass Index ◽  
Body Weight ◽  
Body Mass ◽  
Adult Height ◽  
Adult Life ◽  
Vegetarian Diet ◽  
Age At Menarche ◽  
Cross Sectional ◽  
Men And Women ◽  
Significant Difference

AbstractObjectiveWe investigated whether life-long adherence to a vegetarian diet is associated with adult height, age at menarche, adult body weight and body mass index (BMI), used as indicators of growth, development and obesity, in a large sample of adults.DesignThis was a cross-sectional study. Anthropometric data and information on age, ethnicity, education, age at menarche and age at becoming a vegetarian were obtained through a questionnaire. Self-reported height and weight were calibrated using predictive equations derived from a previous validation study.SettingUnited Kingdom.SubjectsThe study includes 45 962 British men and women aged ≥ 20 years of whom 16 083 were vegetarians (not eating fish or meat).ResultsIn men and women, there were no significant differences in height, weight or BMI between life-long vegetarians (n= 125 (men) andn= 265 (women)) and people who became vegetarian at age ≥ 20 years (n= 3122 (men) andn= 8137 (women)). Nor was there a significant difference in age at menarche between life-long vegetarian women and women who became vegetarian at age ≥ 20 years.ConclusionThis study suggests that, compared with people who become vegetarian when adult, life-long vegetarians do not differ in adult height, weight, BMI or age at menarche in women.

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