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Aladdin H Shadyab, Charles Kooperberg, Alexander P Reiner, Sonia Jain, JoAnn E Manson, Chancellor Hohensee, Caroline A Macera, Richard A Shaffer, Linda C Gallo, Andrea Z LaCroix
BACKGROUND: No study has evaluated whether genetic factors are associated with longevity in African Americans or Hispanics, and it is unclear whether genetic factors are associated with healthy aging. METHODS: In this prospective study, we determined whether 14 genetic variants previously associated with longevity in genome-wide association studies were associated with survival to ages 85 and 90 in 11,053 postmenopausal white, African American, and Hispanic women from the Women's Health Initiative...
October 5, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Ji Yeon Hwang, Ji Seon Shim, Min-Young Song, Sung-Vin Yim, Seung Eun Lee, Kang-Sik Park
BACKGROUND: The ginsenoside Rb1 (Rb1) is the most abundant compound in the root of Panax ginseng. Recent studies have shown that Rb1 has a neuroprotective effect. However, the mechanisms underlying this effect are still unknown. METHODS: We used stable isotope labeling with amino acids in cell culture, combined with quantitative mass spectrometry, to explore a potential protective mechanism of Rb1 in β-amyloid-treated neuronal cells. RESULTS: A total of 1,231 proteins were commonly identified from three replicate experiments...
July 2016: Journal of Ginseng Research
Lebriz Altay, Paula Scholz, Tina Schick, Moritz Felsch, Carel B Hoyng, Anneke I den Hollander, Thomas Langmann, Sascha Fauser
PURPOSE: We evaluated the association of hyperreflective foci (HF) observed in early and intermediate age-related macular degeneration (AMD) with known AMD risk alleles. METHODS: In this pilot case-control study, HF were defined as lesions with reflectivity equal or higher than the retinal pigment epithelium band in spectral domain optical coherence tomography (SDOCT). Hyperreflective foci in the outer nuclear layer and photoreceptor complex were evaluated in 518 individuals with early and intermediate AMD...
August 1, 2016: Investigative Ophthalmology & Visual Science
Nicola Mammarella, Alberto Di Domenico, Beth Fairfield
Better memory for positive information compared to negative and neutral information has been repeatedly associated with successful aging. The main psychological explanations for this so-called "positivity effect" in memory principally rely on emotional, motivational, and cognitive mechanisms that make older adults' cognition highly sensitive to positive information according to ultimate goals of well-being. However, emerging evidence also delineates a genetic profile for positivity effects in memory, which may render some older adults more prone than others to encoding and remembering positive memories...
September 2016: Experimental Gerontology
Hao Huang, Jun Zhao, Biyun Xu, Xu Ma, Qiaoyun Dai, Taishun Li, Fangjing Xue, Bingwei Chen
Largescale genome-wide association studies (GWAS) showed that the TOMM40 rs2075650 polymorphism is significantly associated with Alzheimer's disease (AD) in Caucasian ancestry and Asian population. Here, we evaluated this association with large-scale samples from selected 12 studies (N=28,515; 10,358 cases and 18,157 controls) through the PubMed, AlzGene, and Google Scholar. We identified a significant association between rs2075650 and AD with P=0.000, OR=4.178 and 95% CI 1.891-9.228. In subgroup analysis, we identified significant association between rs2075650 polymorphism and AD in both Asian and Caucasians but not mixed populations...
August 15, 2016: Neuroscience Letters
Alexandra M V Wennberg, Adam P Spira, Corinne Pettigrew, Anja Soldan, Vadim Zipunnikov, George W Rebok, Allen D Roses, Michael W Lutz, Michael M Miller, Madhav Thambisetty, Marilyn S Albert
Type II diabetes mellitus (DM) increases risk for cognitive decline and is associated with brain atrophy in older demented and non-demented individuals. We investigated (1) the cross-sectional association between fasting blood glucose level and cortical thickness in a sample of largely middle-aged, cognitively normal adults, and (2) whether these associations were modified by genes associated with both lipid processing and dementia. To explore possible modifications by genetic status, we investigated the interaction between blood glucose levels and the apolipoprotein E (APOE) ε4 allele and the translocase of the outer mitochondrial membrane (TOMM) 40 '523 genotype on cortical thickness...
June 15, 2016: Journal of the Neurological Sciences
James P Cook, Andrew P Morris
Genome-wide association studies (GWAS) have traditionally been undertaken in homogeneous populations from the same ancestry group. However, with the increasing availability of GWAS in large-scale multi-ethnic cohorts, we have evaluated a framework for detecting association of genetic variants with complex traits, allowing for population structure, and developed a powerful test of heterogeneity in allelic effects between ancestry groups. We have applied the methodology to identify and characterise loci associated with susceptibility to type 2 diabetes (T2D) using GWAS data from the Resource for Genetic Epidemiology on Adult Health and Aging, a large multi-ethnic population-based cohort, created for investigating the genetic and environmental basis of age-related diseases...
August 2016: European Journal of Human Genetics: EJHG
Allen Roses, Scott Sundseth, Ann Saunders, William Gottschalk, Dan Burns, Michael Lutz
The methodology of Genome-Wide Association Screening (GWAS) has been applied for more than a decade. Translation to clinical utility has been limited, especially in Alzheimer's Disease (AD). It has become standard practice in the analyses of more than two dozen AD GWAS studies to exclude the apolipoprotein E (APOE) region because of its extraordinary statistical support, unique thus far in complex human diseases. New genes associated with AD are proposed frequently based on SNPs associated with odds ratio (OR) < 1...
June 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Michael W Lutz, Scott S Sundseth, Daniel K Burns, Ann M Saunders, Kathleen M Hayden, James R Burke, Kathleen A Welsh-Bohmer, Allen D Roses
BACKGROUND: A straightforward, reproducible blood-based test that predicts age dependent risk of Alzheimer's disease (AD) could be used as an enrichment tool for clinical development of therapies. This study evaluated the prognostic performance of a genetics-based biomarker risk algorithm (GBRA) established on a combination of Apolipoprotein E (APOE)/Translocase of outer mitochondrial membrane 40 homolog (TOMM40) genotypes and age, then compare it to cerebrospinal fluid (CSF) biomarkers, neuroimaging and neurocognitive tests using data from two independent AD cohorts...
January 1, 2016: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Michael W Lutz, Donna Crenshaw, Kathleen A Welsh-Bohmer, Daniel K Burns, Allen D Roses
Clinical trials for Alzheimer's disease are now focusing on the earliest stages of the disease with the goal of delaying dementia onset. There is great utility in using genetic variants to identify individuals at high age-dependent risk when the goal is to begin treatment before the development of any cognitive symptoms. Genetic variants identified through large-scale genome-wide association studies have not substantially improved the accuracy provided by APOE genotype to identify people at high risk of late-onset Alzheimer's disease (LOAD)...
May 2016: Current Neurology and Neuroscience Reports
Jenny Ortega-Rojas, Luis Morales, Esneyder Guerrero, Carlos E Arboleda-Bustos, Adriana Mejia, Diego Forero, Luis Lopez, Rodrigo Pardo, Gonzalo Arboleda, Juan Yunis, Humberto Arboleda
OBJECTIVE: We evaluated the association of several single-nucleotide polymorphisms in different genes including APOE, TOMM40, CR1, PVRL2, SORL1, PICALM, and GWA_14q32.13 in a Colombian sample of Late-Onset Alzheimer disease (LOAD) patients. METHODS: A case-control study was conducted in 362 individuals (181 LOADs and 181 controls) to determine the association of single-nucleotide polymorphisms in APOE (e2, e3, and e4), TOMM40 (rs2075650), CR1 (rs665640), PVRL2 (rs6859), SORL1 (rs11218304), PICALM (rs3851179), and GWA_14q32...
March 28, 2016: Alzheimer Disease and Associated Disorders
Luke C Pilling, Janice L Atkins, Kirsty Bowman, Samuel E Jones, Jessica Tyrrell, Robin N Beaumont, Katherine S Ruth, Marcus A Tuke, Hanieh Yaghootkar, Andrew R Wood, Rachel M Freathy, Anna Murray, Michael N Weedon, Luting Xue, Kathryn Lunetta, Joanne M Murabito, Lorna W Harries, Jean-Marie Robine, Carol Brayne, George A Kuchel, Luigi Ferrucci, Timothy M Frayling, David Melzer
Variation in human lifespan is 20 to 30% heritable in twins but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's data, excluding early deaths). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested. In GWAS, a nicotine receptor locus(CHRNA3, previously associated with increased smoking and lung cancer) was associated with fathers' survival...
March 2016: Aging
Friederike Flachsbart, David Ellinghaus, Liljana Gentschew, Femke-Anouska Heinsen, Amke Caliebe, Lene Christiansen, Marianne Nygaard, Kaare Christensen, Hélène Blanché, Jean-François Deleuze, Céline Derbois, Pilar Galan, Carsten Büning, Stephan Brand, Anette Peters, Konstantin Strauch, Martina Müller-Nurasyid, Per Hoffmann, Markus M Nöthen, Wolfgang Lieb, Andre Franke, Stefan Schreiber, Almut Nebel
Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip  = 7...
June 2016: Aging Cell
Jonathan M Schott, Sebastian J Crutch, Minerva M Carrasquillo, James Uphill, Tim J Shakespeare, Natalie S Ryan, Keir X Yong, Manja Lehmann, Nilufer Ertekin-Taner, Neill R Graff-Radford, Bradley F Boeve, Melissa E Murray, Qurat Ul Ain Khan, Ronald C Petersen, Dennis W Dickson, David S Knopman, Gil D Rabinovici, Bruce L Miller, Aida Suárez González, Eulogio Gil-Néciga, Julie S Snowden, Jenny Harris, Stuart M Pickering-Brown, Eva Louwersheimer, Wiesje M van der Flier, Philip Scheltens, Yolande A Pijnenburg, Douglas Galasko, Marie Sarazin, Bruno Dubois, Eloi Magnin, Daniela Galimberti, Elio Scarpini, Stefano F Cappa, John R Hodges, Glenda M Halliday, Lauren Bartley, Maria C Carrillo, Jose T Bras, John Hardy, Martin N Rossor, John Collinge, Nick C Fox, Simon Mead
INTRODUCTION: The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain. METHODS: We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome-wide association study. RESULTS: We confirm that variation in/near APOE/TOMM40 (P = 6 × 10(-14)) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2...
August 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
David T Liebers, Mehdi Pirooznia, Fayaz Seiffudin, Katherine L Musliner, Peter P Zandi, Fernando S Goes
Cognitive impairment is a common feature of the major psychotic disorders, with deficits often present in at risk individuals and unaffected first-degree relatives. Previous studies have suggested that polygenic risk scores (PRS) for schizophrenia (SCZ) are associated with cognitive deficits, but there has been little examination of this association in longitudinal datasets, or comparison with other disorders. We used mixed models to study the association between PRS for 4 adult onset psychiatric disorders with cross-sectional cognitive performance and longitudinal cognitive decline in 8616 older adults from the Health and Retirement Study (HRS), followed for an average of 10 years...
July 2016: Schizophrenia Bulletin
Jie Bao, Xiao-jie Wang, Zong-fu Mao
BACKGROUND: Alzheimer disease (AD) has become an epidemic within the growing elderly population and effective therapies of AD have not been discovered. Genetic factors accounted for over 70% of the incidence of AD and the disease-related polymorphisms are located on chromosome 19, which is one of several prominent chromosomes related to the development of AD. Many inconsistent associations between polymorphisms in ABCA7, CD33, and TOMM40 genes and the susceptibility to AD have been suggested by several independent studies...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
A Payton, P Sindrewicz, V Pessoa, H Platt, M Horan, W Ollier, V J Bubb, N Pendleton, J P Quinn
The Translocase of Outer Mitochondrial Membrane 40 Homolog and Apolipoprotein E (TOMM40-APOE) locus has been associated with a number of age-related phenotypes in humans including nonpathologic cognitive aging, late-onset Alzheimer's disease, and longevity. Here, we investigate the influence of the TOMM40 intron 6 poly-T variant (rs10524523) on TOMM40 gene expression and cognitive abilities and decline in a cohort of 1613 community-dwelling elderly volunteers who had been followed for changes in cognitive functioning over a period of 14 years (range = 12-18 years)...
March 2016: Neurobiology of Aging
Bin Jiao, Xiaoyan Liu, Lin Zhou, Maggie Haitian Wang, Yafang Zhou, Tingting Xiao, Weiwei Zhang, Rui Sun, Mary Miu Yee Waye, Beisha Tang, Lu Shen
Recently, a number of single nucleotide polymorphisms (SNPs) were identified to be associated with late-onset Alzheimer disease (LOAD) through genome-wide association study data. Identification of SNP-SNP interaction played an important role in better understanding genetic basis of LOAD. In this study, fifty-eight SNPs were screened in a cohort of 229 LOAD cases and 318 controls from mainland China, and their interaction was evaluated by a series of analysis methods. Seven risk SNPs and six protective SNPs were identified to be associated with LOAD...
2015: PloS One
Kristen Fortney, Edgar Dobriban, Paolo Garagnani, Chiara Pirazzini, Daniela Monti, Daniela Mari, Gil Atzmon, Nir Barzilai, Claudio Franceschi, Art B Owen, Stuart K Kim
We developed a new statistical framework to find genetic variants associated with extreme longevity. The method, informed GWAS (iGWAS), takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity. To gain support for our approach, we first show there is an overlap between loci involved in disease and loci associated with extreme longevity. These results indicate that several disease variants may be depleted in centenarians versus the general population...
December 2015: PLoS Genetics
Benoit Lehallier, Laurent Essioux, Javier Gayan, Roxana Alexandridis, Tania Nikolcheva, Tony Wyss-Coray, Markus Britschgi
Importance: A reliable method of detecting Alzheimer disease (AD) in its prodromal state is needed for patient stratification in clinical trials or for personalizing existing or potential upcoming therapies. Current cerebrospinal fluid (CSF)- or imaging-based single biomarkers for AD offer reliable identification of patients with underlying AD but insufficient prediction of the rate of AD progression. Objective: To optimize prediction of progression from mild cognitive impairment (MCI) to AD dementia by combining information from diverse patient variables...
December 14, 2015: JAMA Neurology
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