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mendelian randomization

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https://www.readbyqxmd.com/read/29471399/from-genome-wide-association-studies-to-mendelian-randomization-novel-opportunities-for-understanding-cardiovascular-disease-causality-pathogenesis-prevention-and-treatment
#1
Marianne Benn, Børge G Nordestgaard
The Mendelian randomization approach is an epidemiologic study design incorporating genetic information into traditional epidemiologic studies to infer causality of biomarkers, risk factors, or lifestyle factors on disease risk. Mendelian randomization studies often draw on novel information generated in genome-wide association studies on causal associations between genetic variants and a risk factor or lifestyle factor. Such information can then be used in a largely unconfounded study design free of reverse causation to understand if and how risk factors and lifestyle factors cause cardiovascular disease...
February 19, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29432934/alpha-1-antitrypsin-deficiency-from-the-lung-to-the-heart
#2
Ivan Curjuric, Medea Imboden, Robert Bettschart, Seraina Caviezel, Julia Dratva, Marco Pons, Thomas Rothe, Arno Schmidt-Trucksäss, Daiana Stolz, Gian Andri Thun, Arnold von Eckardstein, Florian Kronenberg, Ilaria Ferrarotti, Nicole M Probst-Hensch
BACKGROUND AND AIMS: Alpha-1 antitrypsin (A1AT) is the most abundant serine protease inhibitor in human blood and exerts important anti-inflammatory and immune-modulatory effects. In combination with smoking or other long-term noxious exposures such as occupational dust and fumes, genetic A1AT deficiency can cause chronic obstructive pulmonary disease, a condition with elevated cardiovascular risk. The effects of A1AT deficiency on cardiovascular risk have hardly been studied today. METHODS: Using data from 2614 adults from the population-based SAPALDIA cohort, we tested associations of serum A1AT and SERPINA1 mutations with carotid intima-media thickness (CIMT, measured by B-mode ultrasonography) or self-reported arterial hypertension or cardiovascular disease in multiple regression models using a Mendelian Randomization like analysis design...
January 31, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29429484/complex-segregation-analysis-of-craniomandibular-osteopathy-in-deutsch-drahthaar-dogs
#3
J Vagt, O Distl
This study investigated familial relationships among Deutsch Drahthaar dogs with craniomandibular osteopathy and examined the most likely mode of inheritance. Sixteen Deutsch Drahthaar dogs with craniomandibular osteopathy were diagnosed using clinical findings, radiography or computed tomography. All 16 dogs with craniomandibular osteopathy had one common ancestor. Complex segregation analyses rejected models explaining the segregation of craniomandibular osteopathy through random environmental variation, monogenic inheritance or an additive sex effect...
January 2018: Veterinary Journal
https://www.readbyqxmd.com/read/29409336/hypolipidemic-drugs-and-diabetes-mellitus-mechanisms-and-data-from-genetic-trials
#4
Theodosios D Filippatos, Thalia Panagiotopoulou, Eleftheria Tzavella, Moses S Elisaf
Clinical trials and meta-analyses have shown that statins can dose dependently increase the incidence of new-onset diabetes mellitus (DM) especially in patients with underlying abnormalities of carbohydrate homeostasis. Mendelian randomization studies support these findings since genetic variants in the gene encoding the target of statins, the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, are associated with increased incidence of new-onset DM, suggesting that the so-called diabetogenic effect of statins is an "on-target effect" possibly related to their main mechanism of action, that is the increased low-density lipoprotein (LDL) receptor expression...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29402374/decreased-serum-pyridoxal-levels-in-schizophrenia-meta-analysis-and-mendelian-randomization-analysis
#5
Yukiko Tomioka, Shusuke Numata, Makoto Kinoshita, Hidehiro Umehara, Shin-Ya Watanabe, Masahito Nakataki, Yoshimi Iwayama, Tomoko Toyota, Masashi Ikeda, Hidenaga Yamamori, Shinji Shimodera, Atsushi Tajima, Ryota Hashimoto, Nakao Iwata, Takeo Yoshikawa, Tetsuro Ohmori
BACKGROUND: Alterations in one-carbon metabolism have been associated with schizophrenia, and vitamin B6 is one of the key components in this pathway. METHODS: We first conducted a case-control study of serum pyridoxal levels and schizophrenia in a large Japanese cohort (n = 1276). Subsequently, we conducted a meta-analysis of association studies (n = 2125). Second, we investigated whether rs4654748, which was identified in a genome-wide association study as a vitamin B6-related single nucleotide polymorphism, was genetically implicated in patients with schizophrenia in the Japanese population (n = 10 689)...
February 2, 2018: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/29398597/acetaminophen-paracetamol-use-modifies-the-sulfation-of-sex-hormones
#6
Isaac V Cohen, Elizabeth T Cirulli, Matthew W Mitchell, Thomas J Jonsson, James Yu, Naisha Shah, Tim D Spector, Lining Guo, J Craig Venter, Amalio Telenti
BACKGROUND: Acetaminophen (paracetamol) is one of the most common medications used for management of pain in the world. There is lack of consensus about the mechanism of action, and concern about the possibility of adverse effects on reproductive health. METHODS: We first established the metabolome profile that characterizes use of acetaminophen, and we subsequently trained and tested a model that identified metabolomic differences across samples from 455 individuals with and without acetaminophen use...
February 1, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29397253/hypertriglyceridemia-and-omega-3-fatty-acids-their-often-overlooked-role-in-cardiovascular-disease-prevention
#7
REVIEW
M Arca, C Borghi, R Pontremoli, G M De Ferrari, F Colivicchi, G Desideri, P L Temporelli
AIMS: This review aims to describe the pathogenic role of triglycerides in cardiometabolic risk, and the potential role of omega-3 fatty acids in the management of hypertriglyceridemia and cardiovascular disease. DATA SYNTHESIS: In epidemiological studies, hypertriglyceridemia correlates with an increased risk of cardiovascular disease, even after adjustment for low density lipoprotein cholesterol (LDL-C) levels. This has been further supported by Mendelian randomization studies where triglyceride-raising common single nucleotide polymorphisms confer an increased risk of developing cardiovascular disease...
November 13, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29390354/common-genetic-variants-in-the-fetub-locus-genetically-predicted-fetuin-b-levels-and-risk-of-insulin-resistance-in-obese-chinese-adults
#8
Zhibin Li, Changqin Liu, Xiulin Shi, Zheng Chen, Dongmei Wang, Long Li, Yichang Tu, Mingzhu Lin, Suhuan Liu, Shuyu Yang, Xuejun Li
Elevated serum fetuin-B is suggested to be associated with insulin resistance, but it is unknown if this association is causal. The aim of this study was to explore the potential causal relationship between fetuin-B and insulin resistance.We used Mendelian randomization analysis by incorporating information of genetic variants in FETUB and serum fetuin-B concentrations with insulin resistance in 1148 obese Chinese adults.Common genetic variants (FETUB rs4686434, rs6785067, and rs3733159) were significantly associated with serum fetuin-B concentrations but not with insulin resistance...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29389382/challenges-in-interpreting-multivariable-mendelian-randomization-might-good-cholesterol-be-good-after-all
#9
EDITORIAL
Michael V Holmes, George Davey Smith
No abstract text is available yet for this article.
February 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29375034/diet-lifestyle-and-risk-of-diabetes-and-glycemic-traits-a-mendelian-randomization-study
#10
Renyu Ding, Tao Huang, Jiali Han
BACKGROUND: Observational studies have demonstrated diet/lifestyle play roles in development of type 2 diabetes (T2DM); however, it remains unclear whether these relationships are causal. METHODS: A two-sample MR approach was used to examine the causal effect of diet/lifestyle upon risk of T2DM and glycemic traits. RESULTS: The protein intake-increasing allele C of FTO was significant associated with higher risk of T2DM (Beta ± SE = 0...
January 29, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29374756/vitamin-d-status-supplementation-and-cardiovascular-disease
#11
REVIEW
Armin Zittermann
This review was conducted to assess the dose-response relationship between vitamin D and cardiovascular disease (CVD) outcomes in humans: Prospective cohort studies indicate a multivariable-adjusted non-linear increase in CVD events at levels of circulating 25-hydroxyvitamin D [25(OH)D] of less than 50 nmol/l. However, Mendelian randomization studies do not support these findings. Although meta-analyses of randomized controlled trials (RCTs) do not rule out small beneficial vitamin D effects on surrogate parameters of CVD risk, such as arterial stiffness, at vitamin D doses equivalent to 1,000-5,333 IU daily, other meta-analyses of RCTs show no reduction in CVD events by vitamin D supplementation...
February 2018: Anticancer Research
https://www.readbyqxmd.com/read/29374233/gwas-of-epigenetic-aging-rates-in-blood-reveals-a-critical-role-for-tert
#12
Ake T Lu, Luting Xue, Elias L Salfati, Brian H Chen, Luigi Ferrucci, Daniel Levy, Roby Joehanes, Joanne M Murabito, Douglas P Kiel, Pei-Chien Tsai, Idil Yet, Jordana T Bell, Massimo Mangino, Toshiko Tanaka, Allan F McRae, Riccardo E Marioni, Peter M Visscher, Naomi R Wray, Ian J Deary, Morgan E Levine, Austin Quach, Themistocles Assimes, Philip S Tsao, Devin Absher, James D Stewart, Yun Li, Alex P Reiner, Lifang Hou, Andrea A Baccarelli, Eric A Whitsel, Abraham Aviv, Alexia Cardona, Felix R Day, Nicholas J Wareham, John R B Perry, Ken K Ong, Kenneth Raj, Kathryn L Lunetta, Steve Horvath
DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA...
January 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29366101/low-25-hydroxyvitamin-d-blood-pressure-hypertension-and-ischemic-stroke-a-mendelian-randomization-study-of-109662-individuals-from-the-general-population
#13
Shoaib Afzal, Børge G Nordestgaard
No abstract text is available yet for this article.
August 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29353277/a-critical-review-of-the-consensus-statement-from-the-european-atherosclerosis-society-consensus-panel-2017
#14
Harumi Okuyama, Tomohito Hamazaki, Rokuro Hama, Yoichi Ogushi, Tetsuyuki Kobayashi, Naoki Ohara, Hajime Uchino
BACKGROUND: The Consensus Statement from the European Atherosclerosis Society (EAS) Consensus Panel 2017 concludes on the basis of 3 different types of clinical studies that low-density lipoprotein (LDL) causes atherosclerotic cardiovascular disease (ASCVD). In Mendelian randomization studies, rare genetic mutations affecting LDL receptor function were found to cause higher or lower LDL-C levels, which are associated with correspondingly altered ASCVD risk. In prospective cohort studies and randomized controlled trials (RCTs) of statins, a remarkably consistent log-linear association was demonstrated between the absolute magnitude of LDL-C exposure and ASCVD risk...
January 19, 2018: Pharmacology
https://www.readbyqxmd.com/read/29339098/vitamin-d-and-nonalcoholic-fatty-liver-disease-bi-directional-mendelian-randomization-analysis
#15
Ningjian Wang, Chi Chen, Li Zhao, Yi Chen, Bing Han, Fangzhen Xia, Jing Cheng, Qin Li, Yingli Lu
BACKGROUND: Vitamin D deficiency is associated with nonalcoholic fatty liver disease (NAFLD) in many cross-sectional studies. However, the causality between them has not been established. We used bi-directional mendelian randomization (MR) analysis to explore the causal relationship between 25-hydroxyvitamin D [25(OH)D] and NAFLD. METHODS: 9182 participants were included from a survey in East China from 2014 to 2016. We calculated weighted genetic risk scores (GRS) for 25(OH)D concentration and NAFLD based on 25(OH)D-related and NAFLD-related single nucleotide polymorphisms...
January 9, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29338727/mendelian-randomization-analysis-to-assess-a-causal-effect-of-haptoglobin-on-macroangiopathy-in-chinese-type-2-diabetes-patients
#16
Shiyun Wang, Jie Wang, Rong Zhang, Tao Wang, Dandan Yan, Zhen He, Feng Jiang, Cheng Hu, Weiping Jia
BACKGROUND: Haptoglobin (Hp) functions as an antioxidant by binding with haemoglobin. We investigated whether serum Hp has a causal effect on macroangiopathy via Mendelian randomization (MR) analysis with common variants of the Hp gene in Chinese patients with type 2 diabetes. METHODS: A total of 5687 type 2 diabetes patients were recruited and genotyped for the Hp gene. Clinical features and vascular imaging tests were applied to diagnose macroangiopathy. The association between common Hp genotypes and macroangiopathy was analyzed in the whole population...
January 16, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29338102/circulating-serum-25-hydroxyvitamin-d-levels-and-bone-mineral-density-mendelian-randomization-study
#17
Susanna C Larsson, Håkan Melhus, Karl Michaëlsson
There is considerable discussion of the importance for increased serum 25-hydroxyvitamin D (S-25OHD) concentration associated with adequacy for bone health. Accordingly, whether long-term high S-25OHD concentration in general positively affects bone mineral density (BMD) is uncertain. We used a Mendelian randomization design to determine the association between genetically increased S-25OHD concentrations and BMD. Five single-nucleotide polymorphisms (SNPs) in or near genes encoding enzymes and carrier proteins involved in vitamin D synthesis or metabolism were used as instrumental variables to genetically predict one standard deviation increase in S-25OHD concentration...
January 16, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29335400/causal-associations-between-risk-factors-and-common-diseases-inferred-from-gwas-summary-data
#18
Zhihong Zhu, Zhili Zheng, Futao Zhang, Yang Wu, Maciej Trzaskowski, Robert Maier, Matthew R Robinson, John J McGrath, Peter M Visscher, Naomi R Wray, Jian Yang
Health risk factors such as body mass index (BMI) and serum cholesterol are associated with many common diseases. It often remains unclear whether the risk factors are cause or consequence of disease, or whether the associations are the result of confounding. We develop and apply a method (called GSMR) that performs a multi-SNP Mendelian randomization analysis using summary-level data from genome-wide association studies to test the causal associations of BMI, waist-to-hip ratio, serum cholesterols, blood pressures, height, and years of schooling (EduYears) with common diseases (sample sizes of up to 405,072)...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29334416/investigating-causal-associations-between-use-of-nicotine-alcohol-caffeine-and-cannabis-a-two-sample-bidirectional-mendelian-randomization-study
#19
Karin J H Verweij, Jorien L Treur, Jacqueline M Vink
BACKGROUND AND AIMS: Epidemiological studies consistently show co-occurrence of use of different addictive substances. Whether these associations are causal or due to overlapping underlying influences remains an important question in addiction research. Methodological advances have made it possible to use published genetic associations to infer causal relationships between phenotypes. In this exploratory study, we used Mendelian randomization (MR) to examine the causality of well-established associations between nicotine, alcohol, caffeine, and cannabis use...
January 15, 2018: Addiction
https://www.readbyqxmd.com/read/29325096/genetic-determinants-of-circulating-estrogen-levels-and-evidence-of-a-causal-effect-of-estradiol-on-bone-density-in-men
#20
Anna L Eriksson, John R B Perry, Andrea D Coviello, Graciela E Delgado, Luigi Ferrucci, Andrew R Hoffman, Ilpo T Huhtaniemi, M Arfan Ikram, Magnus K Karlsson, Marcus E Kleber, Gail A Laughlin, Yongmei Liu, Mattias Lorentzon, Kathryn L Lunetta, Dan Mellström, Joanne M Murabito, Anna Murray, Maria Nethander, Carrie M Nielson, Inga Prokopenko, Stephen R Pye, Leslie J Raffel, Fernando Rivadeneira, Priya Srikanth, Lisette Stolk, Alexander Teumer, Thomas G Travison, André G Uitterlinden, Dhananjay Vaidya, Dirk Vanderschueren, Joseph M Zmuda, Winfried März, Eric S Orwoll, Pamela Ouyang, Liesbeth Vandenput, Frederick C W Wu, Frank H de Jong, Shalender Bhasin, Douglas P Kiel, Claes Ohlsson
Context: Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability. No genome-wide association study (GWAS) of estrogen levels has been performed in men of European origin. Objective: To investigate the genetic regulation of serum E2 and E1 in men. Design, setting and participants: GWAS in 11,097 men of European origin from nine epidemiological cohorts. Main Outcome Measures: Genetic determinants of serum E2 and E1 levels...
January 9, 2018: Journal of Clinical Endocrinology and Metabolism
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