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https://www.readbyqxmd.com/read/28812575/response-to-challenge-in-interpretation-of-mendelian-randomization-studies-using-lactase-persistence-as-instrumental-variable
#1
Q Yang, C M Schooling
No abstract text is available yet for this article.
August 16, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28812574/challenge-in-interpretation-of-mendelian-randomization-studies-using-lactase-persistence-as-instrumental-variable
#2
L E T Vissers, Y T van der Schouw, I Sluijs
No abstract text is available yet for this article.
August 16, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28797893/genetic-association-of-telomere-length-with-hepatocellular-carcinoma-risk-a-mendelian-randomization-analysis
#3
Yue Cheng, Chengxiao Yu, Mingtao Huang, Fangzhi Du, Ci Song, Zijian Ma, Xiangjun Zhai, Yuan Yang, Jibin Liu, Jin-Xin Bei, Weihua Jia, Guangfu Jin, Shengping Li, Weiping Zhou, Jianjun Liu, Juncheng Dai, Zhibin Hu
BACKGROUND: Observational studies show an association between telomere length and Hepatocellular carcinoma (HCC) risk, but the relationship is controversial. Particularly, it remains unclear whether the association is due to confounding or biases inherent in conventional epidemiological studies. Here, we applied Mendelian randomization approach to evaluate whether telomere length is causally associated with HCC risk. METHODS: Individual-level data were from HBV-related HCC Genome-wide association studies (1,538 HBV positive HCC patients and 1,465 HBV positive controls)...
August 7, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28797570/genetic-variants-related-to-longer-telomere-length-are-associated-with-increased-risk-of-renal-cell-carcinoma
#4
Mitchell J Machiela, Jonathan N Hofmann, Robert Carreras-Torres, Kevin M Brown, Mattias Johansson, Zhaoming Wang, Matthieu Foll, Peng Li, Nathaniel Rothman, Sharon A Savage, Valerie Gaborieau, James D McKay, Yuanqing Ye, Marc Henrion, Fiona Bruinsma, Susan Jordan, Gianluca Severi, Kristian Hveem, Lars J Vatten, Tony Fletcher, Kvetoslava Koppova, Susanna C Larsson, Alicja Wolk, Rosamonde E Banks, Peter J Selby, Douglas F Easton, Paul Pharoah, Gabriella Andreotti, Laura E Beane Freeman, Stella Koutros, Demetrius Albanes, Satu Mannisto, Stephanie Weinstein, Peter E Clark, Todd E Edwards, Loren Lipworth, Susan M Gapstur, Victoria L Stevens, Hallie Carol, Matthew L Freedman, Mark M Pomerantz, Eunyoung Cho, Peter Kraft, Mark A Preston, Kathryn M Wilson, J Michael Gaziano, Howard S Sesso, Amanda Black, Neal D Freedman, Wen-Yi Huang, John G Anema, Richard J Kahnoski, Brian R Lane, Sabrina L Noyes, David Petillo, Leandro M Colli, Joshua N Sampson, Celine Besse, Helene Blanche, Anne Boland, Laurie Burdette, Egor Prokhortchouk, Konstantin G Skryabin, Meredith Yeager, Mirjana Mijuskovic, Miodrag Ognjanovic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Neonila Szeszenia-Dabrowska, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, H Bas Bueno-de-Mesquita, Federico Canzian, Eric J Duell, Börje Ljungberg, Raviprakash T Sitaram, Ulrike Peters, Emily White, Garnet L Anderson, Lisa Johnson, Juhua Luo, Julie Buring, I-Min Lee, Wong-Ho Chow, Lee E Moore, Christopher Wood, Timothy Eisen, James Larkin, Toni K Choueiri, G Mark Lathrop, Bin Tean Teh, Jean-Francois Deleuze, Xifeng Wu, Richard S Houlston, Paul Brennan, Stephen J Chanock, Ghislaine Scelo, Mark P Purdue
BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations...
August 7, 2017: European Urology
https://www.readbyqxmd.com/read/28795686/hdl-and-atherosclerotic-cardiovascular-disease-genetic-insights-into-complex-biology
#5
REVIEW
Robert S Rosenson, H Bryan Brewer, Philip J Barter, Johan L M Björkegren, M John Chapman, Daniel Gaudet, Daniel Seung Kim, Eric Niesor, Kerry-Anne Rye, Frank M Sacks, Jean-Claude Tardif, Robert A Hegele
Plasma levels of HDL cholesterol (HDL-C) predict the risk of cardiovascular disease at the epidemiological level, but a direct causal role for HDL in cardiovascular disease remains controversial. Studies in animal models and humans with rare monogenic disorders link only particular HDL-associated mechanisms with causality, including those mechanisms related to particle functionality rather than cholesterol content. Mendelian randomization studies indicate that most genetic variants that affect a range of pathways that increase plasma HDL-C levels are not usually associated with reduced risk of cardiovascular disease, with some exceptions, such as cholesteryl ester transfer protein variants...
August 10, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28774656/plasma-apolipoprotein-e-levels-and-risk-of-dementia-a-mendelian-randomization-study-of-106-562-individuals
#6
Katrine L Rasmussen, Anne Tybjærg-Hansen, Børge G Nordestgaard, Ruth Frikke-Schmidt
INTRODUCTION: In recent prospective studies, low plasma levels of apolipoprotein E (apoE) are associated with high risk of dementia. Whether this reflects a causal association remains to be established. METHODS: Using a Mendelian randomization approach, we studied 106,562 and 75,260 individuals from the general population in observational and genetic analyses, respectively. RESULTS: In observational analyses risk of Alzheimer disease and all dementia increased stepwise as a function of stepwise lower apoE levels (P for trend, 2 × 10(-17) and 9 × 10(-21))...
July 27, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28765276/vascular-endothelial-growth-factor-and-ischemic-heart-disease-risk-a-mendelian-randomization-study
#7
Shiu Lun Au Yeung, Hugh Simon Hung San Lam, C Mary Schooling
BACKGROUND: Vascular endothelial growth factor (VEGF) has angiogenic and possibly proatherosclerotic properties. Observationally it is positively associated with cardiovascular disease, although these observations could be confounded or due to reverse causation. We assessed ischemic heart disease (IHD) risk by genetically predicted VEGF, ie, using Mendelian randomization. METHODS AND RESULTS: Single nucleotide polymorphisms (SNPs) predicting VEGF level, at genome-wide significance, were applied to the CARDIoGRAMplusC4D 1000 Genomes-based genome-wide association study IHD case (n=60 801)-control (n=123 504) study...
August 1, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28763444/childhood-adiposity-and-risk-of-type-1-diabetes-a-mendelian-randomization-study
#8
J C Censin, Christoph Nowak, Nicholas Cooper, Peter Bergsten, John A Todd, Tove Fall
BACKGROUND: The incidence of type 1 diabetes (T1D) is increasing globally. One hypothesis is that increasing childhood obesity rates may explain part of this increase, but, as T1D is rare, intervention studies are challenging to perform. The aim of this study was to assess this hypothesis with a Mendelian randomization approach that uses genetic variants as instrumental variables to test for causal associations. METHODS AND FINDINGS: We created a genetic instrument of 23 single nucleotide polymorphisms (SNPs) associated with childhood adiposity in children aged 2-10 years...
August 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28761095/associations-between-subjective-well-being-and-subcortical-brain-volumes
#9
D Van 't Ent, A den Braber, B M L Baselmans, R M Brouwer, C V Dolan, H E Hulshoff Pol, E J C de Geus, M Bartels
To study the underpinnings of individual differences in subjective well-being (SWB), we tested for associations of SWB with subcortical brain volumes in a dataset of 724 twins and siblings. For significant SWB-brain associations we probed for causal pathways using Mendelian Randomization (MR) and estimated genetic and environmental contributions from twin modeling. Another independent measure of genetic correlation was obtained from linkage disequilibrium (LD) score regression on published genome-wide association summary statistics...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760659/no-causal-association-between-25-hydroxyvitamin-d-and-features-of-skin-aging-evidence-from-a-bidirectional-mendelian-randomization-study
#10
Raymond Noordam, Merel A Hamer, Luba M Pardo, Tamara van der Nat, Jessica C Kiefte-de Jong, Manfred Kayser, P Eline Slagboom, André Uitterlinden, M Carola Zillikens, Marian Beekman, Tamar Nijsten, Diana van Heemst, David A Gunn
Data from in-vitro experiments suggest vitamin D reduces the rate of skin aging whereas population studies suggest the opposite, most likely due to confounding by UV-exposure. We investigated whether there are causal associations between 25-hydroxyvitamin D concentrations and features of skin aging in a bidirectional Mendelian Randomization Study. In the Rotterdam Study (N=3,831; 58.2% women, median age 66.5 years) and Leiden Longevity Study (N=661; 50.5% women, median age 63.1 years), facial skin aging features (perceived age, wrinkling, pigmented spots) were assessed either manually or digitally...
July 28, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28754456/hdl-cholesterol-ldl-cholesterol-and-triglycerides-as-risk-factors-for-ckd-a-mendelian-randomization-study
#11
Matthew B Lanktree, Sébastien Thériault, Michael Walsh, Guillaume Paré
BACKGROUND: High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations are heritable risk factors for vascular disease, but their role in the progression of chronic kidney disease (CKD) is unclear. STUDY DESIGN: 2-sample Mendelian randomization analysis of data derived from the largest published lipid and CKD studies. SETTING & PARTICIPANTS: Effect of independent genetic variants significantly associated with lipid concentrations was obtained from the Global Lipids Genetics Consortium (n=188,577), and the effect of these same variants on estimated glomerular filtration rate (eGFR), CKD (defined as eGFR<60mL/min/1...
July 26, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28748955/bayesian-association-scan-reveals-loci-associated-with-human-lifespan-and-linked-biomarkers
#12
Aaron F McDaid, Peter K Joshi, Eleonora Porcu, Andrea Komljenovic, Hao Li, Vincenzo Sorrentino, Maria Litovchenko, Roel P J Bevers, Sina Rüeger, Alexandre Reymond, Murielle Bochud, Bart Deplancke, Robert W Williams, Marc Robinson-Rechavi, Fred Paccaud, Valentin Rousson, Johan Auwerx, James F Wilson, Zoltán Kutalik
The enormous variation in human lifespan is in part due to a myriad of sequence variants, only a few of which have been revealed to date. Since many life-shortening events are related to diseases, we developed a Mendelian randomization-based method combining 58 disease-related GWA studies to derive longevity priors for all HapMap SNPs. A Bayesian association scan, informed by these priors, for parental age of death in the UK Biobank study (n=116,279) revealed 16 independent SNPs with significant Bayes factor at a 5% false discovery rate (FDR)...
July 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28747331/assessing-the-causal-role-of-adiposity-on-disordered-eating-in-childhood-adolescence-and-adulthood-a-mendelian-randomization-analysis
#13
Zoe E Reed, Nadia Micali, Cynthia M Bulik, George Davey Smith, Kaitlin H Wade
Background: Observational studies have shown that higher body mass index (BMI) is associated with increased risk of developing disordered eating patterns. However, the causal direction of this relation remains ambiguous.Objective: We used Mendelian randomization (MR) to infer the direction of causality between BMI and disordered eating in childhood, adolescence, and adulthood.Design: MR analyses were conducted with a genetic score as an instrumental variable for BMI to assess the causal effect of BMI at age 7 y on disordered eating patterns at age 13 y with the use of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4473)...
July 26, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28742912/association-of-genetic-variants-related-to-serum-calcium-levels-with-coronary-artery-disease-and-myocardial-infarction
#14
Susanna C Larsson, Stephen Burgess, Karl Michaëlsson
Importance: Serum calcium has been associated with cardiovascular disease in observational studies and evidence from randomized clinical trials indicates that calcium supplementation, which raises serum calcium levels, may increase the risk of cardiovascular events, particularly myocardial infarction. Objective: To evaluate the potential causal association between genetic variants related to elevated serum calcium levels and risk of coronary artery disease (CAD) and myocardial infarction using mendelian randomization...
July 25, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28729448/network-mendelian-randomization-study-design-to-assess-factors-mediating-the-causal-link-between-telomere-length-and-heart-disease
#15
EDITORIAL
R Garrett Morgan
No abstract text is available yet for this article.
July 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28726810/a-randomized-controlled-trial-of-disclosing-genetic-risk-information-for-alzheimer-disease-via-telephone
#16
Kurt D Christensen, Wendy R Uhlmann, J Scott Roberts, Erin Linnenbringer, Peter J Whitehouse, Charmaine D M Royal, Thomas O Obisesan, L Adrienne Cupples, Melissa B Butson, Grace-Ann Fasaye, Susan Hiraki, Clara A Chen, Uwe Siebert, Robert Cook-Deegan, Robert C Green
PurposeTelephone disclosure of genetic test results can improve access to services. To date, studies of its impact have focused on return of Mendelian risk information, principally hereditary cancer syndromes.MethodsIn a multisite trial of Alzheimer disease genetic risk disclosure, asymptomatic adults were randomized to receive test results in person or via telephone. Primary analyses examined patient outcomes 12 months after disclosure.ResultsData from 257 participants showed that telephone disclosure occurred 7...
July 20, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28711986/single-nucleotide-polymorphisms-associated-with-reading-ability-show-connection-to-socio-economic-outcomes
#17
Michelle Luciano, Saskia P Hagenaars, Simon R Cox, William David Hill, Gail Davies, Sarah E Harris, Ian J Deary, David M Evans, Nicholas G Martin, Margaret J Wright, Timothy C Bates
Impairments in reading and in language have negative consequences on life outcomes, but it is not known to what extent genetic effects influence this association. We constructed polygenic scores for difficulties with language and learning to read from genome-wide data in ~6,600 children, adolescents and young adults, and tested their association with health, socioeconomic outcomes and brain structure measures collected in adults (maximal N = 111,749). Polygenic risk of reading difficulties was associated with reduced income, educational attainment, self-rated health and verbal-numerical reasoning (p < 0...
July 15, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28709925/the-infinitesimal-model-definition-derivation-and-implications
#18
N H Barton, A M Etheridge, A Véber
Our focus here is on the infinitesimal model. In this model, one or several quantitative traits are described as the sum of a genetic and a non-genetic component, the first being distributed within families as a normal random variable centred at the average of the parental genetic components, and with a variance independent of the parental traits. Thus, the variance that segregates within families is not perturbed by selection, and can be predicted from the variance components. This does not necessarily imply that the trait distribution across the whole population should be Gaussian, and indeed selection or population structure may have a substantial effect on the overall trait distribution...
July 11, 2017: Theoretical Population Biology
https://www.readbyqxmd.com/read/28701353/known-and-unknowns-in-the-care-of-paediatric-familial-hypercholesterolaemia
#19
Andrew C Martin, Samuel S Gidding, Albert Wiegman, Gerald F Watts
Familial hypercholesterolaemia (FH) is a common genetic disorder that causes elevated low-density lipoprotein (LDL)-cholesterol levels from birth. Untreated FH accelerates atherosclerosis and predisposes individuals to premature coronary artery disease (CAD) in adulthood. Mendelian randomization studies have demonstrated that LDL-cholesterol has both a causal and cumulative effect on the risk of CAD. This supports clinical recommendations that children with FH commence pharmacological treatment from age 8-10 years, to reduce the burden of hypercholesterolaemia...
July 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28684612/the-effect-of-iron-status-on-risk-of-coronary-artery-disease-a-mendelian-randomization-study
#20
Dipender Gill, Fabiola Del Greco M, Ann P Walker, Surjit K S Srai, Michael A Laffan, Cosetta Minelli
OBJECTIVE: Iron status is a modifiable trait that has been implicated in cardiovascular disease. This study uses the Mendelian randomization technique to investigate whether there is any causal effect of iron status on risk of coronary artery disease (CAD). APPROACH AND RESULTS: A 2-sample Mendelian randomization approach is used to estimate the effect of iron status on CAD risk. Three loci (rs1800562 and rs1799945 in the HFE gene and rs855791 in TMPRSS6) that are each associated with serum iron, transferrin saturation, ferritin, and transferrin in a pattern suggestive of an association with systemic iron status are used as instruments...
July 6, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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