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mendelian randomization

Camilla J Kobylecki, Shoaib Afzal, Børge G Nordestgaard
BACKGROUND: Observationally, high plasma urate is associated with high risk of cancer. We using a Mendelian randomization design to test the hypothesis that high concentrations of plasma urate are associated with high cancer incidence and all-cause mortality observationally and genetically. METHODS: We performed observational and genetic analyses using plasma urate and the urate solute carrier family 2 member 9 (SLC2A9) rs7442295 genotype in 86210 individuals from the Copenhagen General Population Study...
April 20, 2017: Clinical Chemistry
Lin Xu, Yuan Tao Hao
Observational studies have reported an association of handgrip strength with risk of cardiovascular disease. However, residual confounding and reverse causation may have influenced these findings. A Mendelian randomization (MR) study was conducted to examine whether handgrip is causally associated with cardiovascular disease. Two single nucleotide polymorphisms (SNPs), rs3121278 and rs752045, were used as the genetic instruments for handgrip. The effect of each SNP on coronary artery disease/myocardial infarction (CAD/MI) was weighted by its effect on handgrip strength, and estimates were pooled to provide a summary measure for the effect of increased handgrip on risk of CAD/MI...
April 19, 2017: Scientific Reports
Matthew L Romo, C Mary Schooling
No abstract text is available yet for this article.
April 19, 2017: Neuroendocrinology
S Hägg, Y Zhan, R Karlsson, L Gerritsen, A Ploner, S J van der Lee, L Broer, J Deelen, R E Marioni, A Wong, A Lundquist, G Zhu, N K Hansell, E Sillanpää, I O Fedko, N A Amin, M Beekman, A J M de Craen, S Degerman, S E Harris, K-J Kan, C M Martin-Ruiz, G W Montgomery, A N Adolfsson, C A Reynolds, N J Samani, H E D Suchiman, A Viljanen, T von Zglinicki, M J Wright, J-J Hottenga, D I Boomsma, T Rantanen, J A Kaprio, D R Nyholt, N G Martin, L Nyberg, R Adolfsson, D Kuh, J M Starr, I J Deary, P E Slagboom, C M van Duijn, V Codd, N L Pedersen
The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP)...
April 18, 2017: Translational Psychiatry
Ambreen Gul, Antonia Harford, Philip Zager
Previous studies have demonstrated an association of serum uric acid with kidney disease. However, it is unknown whether this relationship is causal. Mendelian randomization takes advantage of allele randomization at birth to assess causation. Using this technique Ahola et al. found strong evidence against causation in Finnish Caucasians with type 1 diabetes mellitus. However, replication in other populations is needed to further assess a potential causal role for hyperuricemia in kidney disease.
May 2017: Kidney International
Megan A Clarke, Corinne E Joshu
Very little is known about the influence of early life exposures on adult cancer risk. The purpose of this narrative review was to summarize the epidemiologic evidence relating early life tobacco use, obesity, diet, and physical activity to adult cancer risk; describe relevant theoretical frameworks and methodological strategies for studying early life exposures; and discuss policies and research initiatives focused on early life. Our findings suggest that in utero exposures may indirectly influence cancer risk by modifying biological pathways associated with carcinogenesis; however, more research is needed to firmly establish these associations...
April 12, 2017: Epidemiologic Reviews
Deborah Lawlor, Rebecca Richmond, Nicole Warrington, George McMahon, George Davey Smith, Jack Bowden, David M Evans
Mendelian randomization (MR), the use of genetic variants as instrumental variables (IVs) to test causal effects, is increasingly used in aetiological epidemiology. Few of the methodological developments in MR have considered the specific situation of using genetic IVs to test the causal effect of exposures in pregnant women on postnatal offspring outcomes. In this paper, we describe specific ways in which the IV assumptions might be violated when MR is used to test such intrauterine effects. We highlight the importance of considering the extent to which there is overlap between genetic variants in offspring that influence their outcome with genetic variants used as IVs in their mothers...
February 14, 2017: Wellcome Open Research
Olena O Yavorska, Stephen Burgess
MendelianRandomization is a software package for the R open-source software environment that performs Mendelian randomization analyses using summarized data. The core functionality is to implement the inverse-variance weighted, MR-Egger and weighted median methods for multiple genetic variants. Several options are available to the user, such as the use of robust regression, fixed- or random-effects models and the penalization of weights for genetic variants with heterogeneous causal estimates. Extensions to these methods, such as allowing for variants to be correlated, can be chosen if appropriate...
April 7, 2017: International Journal of Epidemiology
Christian A Gleissner, Christian Erbel, Fabian Linden, Gabriele Domschke, Mohammadreza Akhavanpoor, Christian M Helmes, Andreas O Doesch, Marcus E Kleber, Hugo A Katus, Winfried Maerz
BACKGROUND AND AIMS: Galectin-3 binding protein (Gal-3BP) has been associated with inflammation and cancer, however, its role in coronary artery disease (CAD) and cardiovascular outcome remains unclear. METHODS: Gal-3BP plasma levels were measured by ELISA in 2922 individuals from the LURIC study (62.7 ± 10.6 years, 62.7% male). All-cause and cardiovascular mortality was assessed by Kaplan-Meier analysis and Cox proportional hazards regression. Causal involvement of Gal-3BP was tested for by Mendelian randomization...
March 23, 2017: Atherosclerosis
Sun Ju Lee, Yon Ho Jee, Keum Ji Jung, Seri Hong, Eun Soon Shin, Sun Ha Jee
BACKGROUND AND PURPOSE: Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. METHODS: The 14 single-nucleotide polymorphisms (SNPs) (<10(-7)) including rs6742078 of uridine diphosphoglucuronyl-transferase were selected from genome-wide association study of bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases...
April 7, 2017: Stroke; a Journal of Cerebral Circulation
T Qiu, Y Z Dong, X M Yu, N Zhao, Y F Yang
We used the conventional and methylation-sensitive randomly amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) analyses to assess genome-wide changes and explore the relationships between genetic and epigenetic variations among individuals of a newly synthesized allohexaploid wheat line whose genomic constitution is identical to that of the natural common wheat, compared with its parent plants and a natural counterpart named Chinese Spring. We found rapid, extensive, and predominantly consistent non-Mendelian changes in the form of genetic and DNA methylation variations in the allohexaploid individuals...
April 5, 2017: Genetics and Molecular Research: GMR
Sonja A Swanson, Miguel A Hernán
Background: Instrumental variable (IV) methods are often used to identify 'local' causal effects in a subgroup of the population of interest. Such 'local' effects may not be ideal for informing clinical or policy decision making. When the instrument is non-causal, additional difficulties arise for interpreting 'local' effects. Little attention has been paid to these difficulties, even though commonly proposed instruments in epidemiology are non-causal (e.g. proxies for physician's preference; genetic variants in some Mendelian randomization studies)...
March 30, 2017: International Journal of Epidemiology
Femke Ng van 't Hof, Julien Vaucher, Michael V Holmes, Arno de Wilde, Annette F Baas, Jan D Blankensteijn, Albert Hofman, Lambertus Alm Kiemeney, Fernando Rivadeneira, André G Uitterlinden, Sita H Vermeulen, Gabriël Je Rinkel, Paul Iw de Bakker, Ynte M Ruigrok
Epidemiological studies show that type 2 diabetes (T2D) is inversely associated with intracranial aneurysms (IA) and abdominal aortic aneurysms (AAA). Although adiposity has not been considered a risk factor for IA, there have been inconsistent reports relating adiposity to AAA risk. We assessed whether these observations have a genetic, causal basis. To this end, we extracted genotypes of validated single-nucleotide polymorphisms associated with T2D (n=65), body mass index (BMI) (n=97) and waist-hip ratio adjusted for BMI (WHRadjBMI) (n=47) from genotype data collected in 717 IA cases and 1988 controls, and in 818 AAA cases and 3004 controls, all of Dutch descent...
April 5, 2017: European Journal of Human Genetics: EJHG
Derek Klarin, Connor A Emdin, Pradeep Natarajan, Mark F Conrad, Sekar Kathiresan
BACKGROUND: UK Biobank is the world's largest repository for phenotypic and genotypic information for individuals of European ancestry. Here, we leverage UK Biobank to understand the inherited basis for venous thromboembolism (VTE), a leading cause of cardiovascular mortality. METHODS AND RESULTS: We identified 3290 VTE cases and 116 868 controls through billing code-based phenotyping. We performed a genome-wide association study for VTE with ≈9 000 000 imputed single-nucleotide polymorphisms...
April 2017: Circulation. Cardiovascular Genetics
M C Borges, I O Oliveira, D F Freitas, B L Horta, K K Ong, D P Gigante, A J D Barros
Background and Aims: The substantial reduction in adiponectin concentration among obese individuals seems to depend on fat distribution and is a marker of metabolic and adipose tissue dysfunction. We aimed to: (i) address whether abdominal fat from different compartments (visceral, deep subcutaneous abdominal and superficial subcutaneous abdominal) and gluteofemoral fat are independently associated with blood adiponectin concentration; and (ii) investigate whether abdominal (proxied by waist circumference) and gluteofemoral fat (proxied by hip circumference) accumulation causally determine blood adiponectin concentration...
March 27, 2017: International Journal of Epidemiology
V Gupta, G K Walia, M P Sachdeva
OBJECTIVES: To assess the current status of Mendelian randomization (MR) approach in effectively influencing the observational epidemiology for examining causal relationships. METHODS: Narrative review on studies related to principle, strengths, limitations, and achievements of MR approach. RESULTS: Observational epidemiological studies have repeatedly produced several beneficiary associations which were discarded when tested by standard randomized controlled trials (RCTs)...
April 2017: Public Health
Milena A Gianfrancesco, Pernilla Stridh, Brooke Rhead, Xiaorong Shao, Edison Xu, Jennifer S Graves, Tanuja Chitnis, Amy Waldman, Timothy Lotze, Teri Schreiner, Anita Belman, Benjamin Greenberg, Bianca Weinstock-Guttman, Gregory Aaen, Jan M Tillema, Janace Hart, Stacy Caillier, Jayne Ness, Yolanda Harris, Jennifer Rubin, Meghan Candee, Lauren Krupp, Mark Gorman, Leslie Benson, Moses Rodriguez, Soe Mar, Ilana Kahn, John Rose, Shelly Roalstad, T Charles Casper, Ling Shen, Hong Quach, Diana Quach, Jan Hillert, Maria Bäärnhielm, Anna Hedstrom, Tomas Olsson, Ingrid Kockum, Lars Alfredsson, Catherine Metayer, Catherine Schaefer, Lisa F Barcellos, Emmanuelle Waubant
OBJECTIVE: To utilize Mendelian randomization to estimate the causal association between low serum vitamin D concentrations, increased body mass index (BMI), and pediatric-onset multiple sclerosis (MS) using genetic risk scores (GRS). METHODS: We constructed an instrumental variable for vitamin D (vitD GRS) by computing a GRS for 3 genetic variants associated with levels of 25(OH)D in serum using the estimated effect of each risk variant. A BMI GRS was also created that incorporates the cumulative effect of 97 variants associated with BMI...
March 29, 2017: Neurology
Fang-Fei Wei, Lutgarde Thijs, Zhen-Yu Zhang, Lotte Jacobs, Wen-Yi Yang, Erika Salvi, Lorena Citterio, Nicholas Cauwenberghs, Tatiana Kuznetsova, Nadja E A Drummen, Azusa Hara, Paolo Manunta, Yan Li, Peter Verhamme, Karel Allegaert, Daniele Cusi, Cees Vermeer, Jan A Staessen
Background.: Vitamin K (VK)-dependent γ-glutamate carboxylation and serine phosphorylation activate matrix Gla protein (MGP) to a potent locally acting inhibitor of calcification. Nephrolithiasis represents a process of unwanted calcification associated with substantial mortality and high recurrence rates. We hypothesized that the risk of nephrolithiasis increases with VK shortage, as exemplified by higher plasma levels of desphospho-uncarboxylated MGP (dp-ucMGP). Methods...
March 15, 2017: Nephrology, Dialysis, Transplantation
Jana Nano, Taulant Muka, Symen Ligthart, Albert Hofman, Sarwa Darwish Murad, Harry LA Janssen, Oscar H Franco, Abbas Dehghan
Background: High levels of serum gamma-glutamyltransferase (GGT) are associated with increased risk of prediabetes and type 2 diabetes in observational studies. It is unclear whether this relationship is causal, arises from residual confounding or is a consequence of reverse causation. Methods: We used data from a prospective population-based cohort study, compromising 8611 individuals without diabetes at baseline. Cox proportional hazard models were used to study the association between serum GGT levels and incident prediabetes and diabetes...
March 13, 2017: International Journal of Epidemiology
Fernando Pires Hartwig, Neil Martin Davies, Gibran Hemani, George Davey Smith
No abstract text is available yet for this article.
March 15, 2017: International Journal of Epidemiology
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