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https://www.readbyqxmd.com/read/28102331/investigating-causality-in-associations-between-smoking-initiation-and-schizophrenia-using-mendelian-randomization
#1
Suzanne H Gage, Hannah J Jones, Amy E Taylor, Stephen Burgess, Stanley Zammit, Marcus R Munafò
Smoking is strongly associated with schizophrenia. Although it has been widely assumed that this reflects self-medication, recent studies suggest that smoking may be a risk factor for schizophrenia. We performed two-sample bi-directional Mendelian randomization using summary level genomewide association data from the Tobacco And Genetics Consortium and Psychiatric Genomics Consortium. Variants associated with smoking initiation and schizophrenia were combined using an inverse-variance weighted fixed-effects approach...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097664/testing-mate-choice-and-overdominance-at-mh-in-natural-families-of-atlantic-salmon-salmo-salar
#2
C Tentelier, O Barroso-Gomila, O Lepais, A Manicki, I Romero-Garmendia, B M Jugo
This study aimed to test mate choice and selection during early life stages on major histocompatibility (MH) genotype in natural families of Atlantic salmon Salmo salar spawners and juveniles, using nine microsatellites to reconstruct families, one microsatellite linked to an MH class I gene and one minisatellite linked to an MH class II gene. MH-based mate choice was only detected for the class I locus on the first year, with lower expected heterozygosity in the offspring of actually mated pairs than predicted under random mating...
January 18, 2017: Journal of Fish Biology
https://www.readbyqxmd.com/read/28095459/association-of-body-mass-index-with-dna-methylation-and-gene-expression-in-blood-cells-and-relations-to-cardiometabolic-disease-a-mendelian-randomization-approach
#3
Michael M Mendelson, Riccardo E Marioni, Roby Joehanes, Chunyu Liu, Åsa K Hedman, Stella Aslibekyan, Ellen W Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R Irvin, Ariella Cohain, Eric E Schadt, Megan L Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F McRae, Sarah E Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, John M Starr, Erica Kleinbrink, Leonard Lipovich, Peter M Visscher, Naomi R Wray, Ronald M Krauss, Daniele Fallin, Andrew Feinberg, Devin M Absher, Myriam Fornage, James S Pankow, Lars Lind, Caroline Fox, Erik Ingelsson, Donna K Arnett, Eric Boerwinkle, Liming Liang, Daniel Levy, Ian J Deary
BACKGROUND: The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. METHODS AND FINDINGS: We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants...
January 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28081156/generation-of-a-stable-transgenic-swine-model-expressing-a-porcine-histone-2b-egfp-fusion-protein-for-cell-tracking-and-chromosome-dynamics-studies
#4
Renan B Sper, Sehwon Koh, Xia Zhang, Sean Simpson, Bruce Collins, Jeff Sommer, Robert M Petters, Ignacio Caballero, Jeff L Platt, Jorge A Piedrahita
Transgenic pigs have become an attractive research model in the field of translational research, regenerative medicine, and stem cell therapy due to their anatomic, genetic and physiological similarities with humans. The development of fluorescent proteins as molecular tags has allowed investigators to track cell migration and engraftment levels after transplantation. Here we describe the development of two transgenic pig models via SCNT expressing a fusion protein composed of eGFP and porcine Histone 2B (pH2B)...
2017: PloS One
https://www.readbyqxmd.com/read/28078998/lipoprotein-a-management-pharmacological-and-apheretic-treatment
#5
Ruth Hanssen, Ioanna Gouni-Berthold
Lipoprotein (a) [Lp(a)] is an low-density lipoprotein (LDL)-like particle with an additional apolipoprotein, apolipoprotein (a), [apo(a)] attached to apolipoprotein B. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) is causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). The risk association between Lp(a) concentrations and CVD is still controversial but seems to be continuous and without an obvious threshold Lp(a) level. Circulating concentrations of Lp(a) are genetically determined; desirable levels are amplt; 50 mg/dl...
12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28073764/causal-effect-of-genetic-variants-associated-with-body-mass-index-on-multiple-sclerosis-susceptibility
#6
Milena A Gianfrancesco, M Maria Glymour, Stefan Walter, Brooke Rhead, Xiaorong Shao, Ling Shen, Hong Quach, Alan Hubbard, Ingileif Jónsdóttir, Kári Stefánsson, Pernilla Strid, Jan Hillert, Anna Hedström, Tomas Olsson, Ingrid Kockum, Catherine Schaefer, Lars Alfredsson, Lisa F Barcellos
Multiple sclerosis (MS) is an autoimmune disease with both genetic and environmental risk factors. Recent studies indicate that childhood and adolescent obesity double the risk of MS, but this association may reflect unmeasured confounders rather than causal effects of obesity. We used separate-sample Mendelian randomization to estimate the causal effect of body mass index (BMI) on susceptibility to MS. Using data from non-Hispanic white members of the Kaiser Permanente Medical Care Plan of Northern California (KPNC) (2006-2014; 1,104 cases of MS and 10,536 controls) and a replication data set from Sweden (the Epidemiological Investigation of MS (EIMS) and the Genes and Environment in MS (GEMS) studies, 2005-2013; 5,133 MS cases and 4,718 controls), we constructed a weighted genetic risk score using 97 variants previously established to predict BMI...
January 9, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28066631/serum-uric-acid-levels-and-cardiovascular-disease-the-gordian-knot
#7
COMMENT
Efrén Martínez-Quintana, Antonio Tugores, Fayna Rodríguez-González
Hyperuricemia is defined as serum uric acid level of more than 7 mg/dL and blood levels of uric acid are causally associated with gout, as implicated by evidence from randomized clinical trials using urate lowering therapies. Uric acid as a cardiovascular risk factor often accompanies metabolic syndrome, hypertension, diabetes, dyslipidemia, chronic renal disease, and obesity. Despite the association of hyperuricemia with cardiovascular risk factors, it has remained controversial as to whether uric acid is an independent predictor of cardiovascular disease...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28063740/high-density-lipoproteins-biology-epidemiology-and-clinical-management
#8
REVIEW
Hong Y Choi, Anouar Hafiane, Adel Schwertani, Jacques Genest
High-density lipoproteins (HDLs) have multiple pleiotropic effects against arteriosclerosis. Most are independent of the cholesterol mass within HDL particles. Yet, HDL cholesterol (HDL-C) remains a biomarker to assess cardiovascular risk. Whereas the epidemiological association between HDL-C and cardiovascular risk is strong, graded and coherent across populations, Mendelian randomization studies cast doubt on whether HDL-C is causally related to atherosclerotic cardiovascular disease. The apparent failure of HDL-C-raising therapies (fibrates, niacin, and cholesteryl ester transfer protein inhibitors) raises questions about the HDL-C hypothesis...
October 20, 2016: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28055004/comprehensive-genotyping-in-dyslipidemia-mendelian-dyslipidemias-caused-by-rare-variants-and-mendelian-randomization-studies-using-common-variants
#9
REVIEW
Hayato Tada, Masa-Aki Kawashiri, Masakazu Yamagishi
Dyslipidemias, especially hyper-low-density lipoprotein cholesterolemia and hypertriglyceridemia, are important causal risk factors for coronary artery disease. Comprehensive genotyping using the 'next-generation sequencing' technique has facilitated the investigation of Mendelian dyslipidemias, in addition to Mendelian randomization studies using common genetic variants associated with plasma lipids and coronary artery disease. The beneficial effects of low-density lipoprotein cholesterol-lowering therapies on coronary artery disease have been verified by many randomized controlled trials over the years, and subsequent genetic studies have supported these findings...
January 5, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28049019/the-causal-role-of-smoking-on-the-risk-of-hip-or-knee-replacement-due-to-primary-osteoarthritis-a-mendelian-randomisation-analysis-of-the-hunt-study
#10
M B Johnsen, G Å Vie, B S Winsvold, J H Bjørngaard, B O Åsvold, M E Gabrielsen, L M Pedersen, A I Hellevik, A Langhammer, O Furnes, G B Flugsrud, F Skorpen, P R Romundstad, K Storheim, L Nordsletten, J A Zwart
OBJECTIVE: Smoking has been associated with a reduced risk of hip and knee osteoarthritis (OA) and subsequent joint replacement. The aim of the present study was to assess whether the observed association is likely to be causal. METHOD: 55,745 participants of a population-based cohort were genotyped for the rs1051730 C > T single-nucleotide polymorphism (SNP), a proxy for smoking quantity among smokers. A Mendelian randomization analysis was performed using rs1051730 as an instrument to evaluate the causal role of smoking on the risk of hip or knee replacement (combined as total joint replacement (TJR))...
January 1, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28039282/relationships-of-measured-and-genetically-determined-height-with-the-cardiac-conduction-system-in-healthy-adults
#11
Thomas Kofler, Sébastien Thériault, Matthias Bossard, Stefanie Aeschbacher, Selina Bernet, Philipp Krisai, Steffen Blum, Martin Risch, Lorenz Risch, Christine M Albert, Guillaume Paré, David Conen
BACKGROUND: Increasing height is an independent risk factor for atrial fibrillation, but the underlying mechanisms are unknown. We hypothesized that height-related differences in electric conduction could be potential mediators of this relationship. METHODS AND RESULTS: We enrolled 2149 adults aged 25 to 41 years from the general population. Height was directly measured, and a resting 12-lead ECG obtained under standardized conditions. Multivariable linear regression models were used to evaluate the association between measured height and ECG parameters...
January 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28038378/the-causal-effects-of-alcohol-on-lipoprotein-subfraction-and-triglyceride-levels-using-a-mendelian-randomization-analysis-the-nagahama-study
#12
Yasuharu Tabara, Hidenori Arai, Yuhko Hirao, Yoshimitsu Takahashi, Kazuya Setoh, Takahisa Kawaguchi, Shinji Kosugi, Yasuki Ito, Takeo Nakayama, Fumihiko Matsuda
BACKGROUND: Light-to-moderate alcohol consumption may increase circulating high-density lipoprotein cholesterol (HDL-C) levels and decrease low-density lipoprotein cholesterol (LDL-C) levels. However, the effect of alcohol on biologically important lipoprotein subfractions remains largely unknown. Here we aimed to clarify the effects of alcohol on lipoprotein subfractions using a Mendelian randomization analysis. METHODS: The study subjects consisted of 8364 general Japanese individuals...
December 22, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28031317/coffee-intake-cardiovascular-disease-and-all-cause-mortality-observational-and-mendelian-randomization-analyses-in-95%C3%A2-000-223%C3%A2-000-individuals
#13
Ask Tybjærg Nordestgaard, Børge Grønne Nordestgaard
BACKGROUND: Coffee has been associated with modestly lower risk of cardiovascular disease and all-cause mortality in meta-analyses; however, it is unclear whether these are causal associations. We tested first whether coffee intake is associated with cardiovascular disease and all-cause mortality observationally; second, whether genetic variations previously associated with caffeine intake are associated with coffee intake; and third, whether the genetic variations are associated with cardiovascular disease and all-cause mortality...
December 28, 2016: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28031309/assessment-of-causality-between-serum-gamma-glutamyltransferase-and-type-2-diabetes-mellitus-using-publicly-available-data-a-mendelian-randomization-study
#14
Raymond Noordam, Roelof A J Smit, Iris Postmus, Stella Trompet, Diana van Heemst
BACKGROUND: In observational studies, high levels of gamma-glutamyltransferase (GGT) have been associated with a higher risk of type 2 diabetes mellitus (T2D). We aimed to assess whether this association is causal, using Mendelian randomization. METHODS: A Mendelian randomization study was conducted using publicly available data from a genome-wide association study (GWAS) on T2D (12 171 cases of T2D and 56 862 controls), and additionally from GWAS on glycaemic traits (N = 46 186) and HbA1c (N = 46 368) in nondiabetic participants...
December 28, 2016: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28025330/serum-calcium-and-risk-of-migraine-a-mendelian-randomization-study
#15
Peter Yin, Verneri Anttila, Katherine M Siewert, Aarno Palotie, George Davey Smith, Benjamin F Voight
Migraine affects ∼14% of the world's population, though not all predisposing causal risk factors are known. We used electronic health records, genetic co-heritability analysis, and a two-sample Mendelian Randomization (MR) design to determine if elevated serum calcium levels were associated with risk of migraine headache. Co-morbidity was evaluated using electronic health records obtained from the PennOmics database comprising >1 million patient entries. Genetic co-heritability and causality via MR was assessed using data from the International Headache Consortium (23,285 cases, 95,425 controls) and circulating serum calcium levels (39,400 subjects)...
December 26, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28025256/commentary-mendelian-randomization-inspired-causal-inference-in-the-absence-of-genetic-data
#16
Luisa Zuccolo, Michael V Holmes
Studying the long-term causal effects of alcohol drinking is notoriously difficult. Epidemiological studies that use conventional analytical approaches are likely to be confounded and affected by reporting/recall bias and reverse causality, specifically in the form of the sick quitter effect (individuals quitting or never starting to consume alcohol due to underlying ill health).(1) Decades of observational data showing J-shaped relationships of alcohol with risk of disease and in particular cardiovascular disease,(2) fuelled by confirmation bias, have resulted in alcohol policies such that individuals are recommended to drink in moderation, due to putative cardioprotective effects...
December 26, 2016: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28007909/mendelian-randomization-estimates-of-alanine-aminotransferase-with-cardiovascular-disease-guangzhou-biobank-cohort-study
#17
Lin Xu, Chao Qiang Jiang, Tai Hing Lam, Wei Sen Zhang, Feng Zhu, Ya Li Jin, G Neil Thomas, Kar Keung Cheng, C Mary Schooling
Observational studies of the association of alanine aminotransferase (ALT) levels with ischaemic heart disease (IHD) and cardiovascular disease (CVD) risk factors are inconsistent, probably because of confounding and reverse causality. Mendelian randomization (MR) provides less confounded results. We used MR analysis to assess the associations of ALT (U/L) with IHD, diabetes and other CVD risk factors. We used instrumental variable analysis based on two single nucleotide polymorphism (SNPs) HSD17B13/MAPK10 (rs6834314) and PNPLA3/SAMM50 (rs738409) to assess the associations of ALT (U/L) with IHD, diabetes and other CVD risk factors in the Guangzhou Biobank Cohort Study (GBCS)...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28007143/genetics-implications-for-prevention-and-management-of-coronary-artery-disease
#18
REVIEW
Themistocles L Assimes, Robert Roberts
An exciting new era has dawned for the prevention and management of coronary artery disease (CAD) utilizing genetic risk variants. The recent identification of over 60 susceptibility loci for CAD confirms not only the importance of established risk factors, but also the existence of many novel causal pathways that are expected to improve our understanding of the genetic basis of CAD and facilitate the development of new therapeutic agents over time. Concurrently, Mendelian randomization studies have provided intriguing insights on the causal relationship between CAD-related traits, and highlight the potential benefits of long-term modifications of risk factors...
December 27, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28000901/identification-of-key-genes-in-colorectal-cancer-using-random-walk-with-restart
#19
Xiaofeng Cui, Kexin Shen, Zhongshi Xie, Tongjun Liu, Haishan Zhang
As the most common type of cancer and the second leading cause of cancer-associated mortality, colorectal cancer (CRC) has received increasing attention. The aim of the present study was to investigate the mechanisms of CRC by analyzing the microarray dataset, GSE32323. The GSE32323 dataset was downloaded from the Gene Expression Omnibus, and included 17 pairs of matched cancer and normal colorectal tissue samples. The differentially expressed genes (DEGs) were screened using the Linear Models for Microarray Data package and a search of CRC genes, also denoted as seed genes, was performed using the Online Mendelian Inheritance in Man database...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27996050/liver-enzymes-and-risk-of-ischemic-heart-disease-and-type-2-diabetes-mellitus-a-mendelian-randomization-study
#20
Junxi Liu, Shiu Lun Au Yeung, Shi Lin Lin, Gabriel M Leung, C Mary Schooling
We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significance applied to extensively genotyped case-control studies of diabetes (DIAGRAM) and coronary artery disease (CAD)/myocardial infarction (MI) (CARDIoGRAMplusC4D 1000 Genomes). Genetically higher ALT was associated with higher risk of diabetes, odds ratio (OR) 2...
December 20, 2016: Scientific Reports
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