Journal Article


Aiden Peter Corvin
Gary (James) Donohoe


Physiotherapy & Sport

genome wide association study risk factors novel genetic influences research and development oxidative stress european commission public health culture and education

Common variants at 12q14 and 12q24 are associated with hippocampal volume. (2012)

Abstract Aging is associated with reductions in hippocampal volume (HV) that are accelerated by Alzheimer?s disease and vascular risk factors. Our genome-wide association study of dementia- free persons (n=9,232) identified 46 SNPs at four loci with p-values <4.0?10 -7 . Two additional samples (n=2,318) replicated associations at 12q24 within MSRB3/WIF1 (discovery + replication, rs17178006; p=5.3?10 -11 ) and at 12q14 near HRK/FBXW8 (rs7294919; p=2.9?10 -11 ). Remaining associations included one 2q24 SNP within DPP4 (rs6741949; p=2.9?10 -7 ) and nine 9p33 SNPs within ASTN2 (rs7852872; p=1.0?10 -7 ) that were also associated with HV (p<0.05) in a third younger, more heterogeneous sample (n=7,794). The ASTN2 SNP was also associated with decline in cognition in a largely independent sample (n=1,563). These associations implicate genes related to apoptosis ( HRK ), development ( WIF1) , oxidative stress ( MSR3B ), ubiquitination ( FBXW8 ), enzymes targeted by new diabetes medications ( DPP4 ), and neuronal migration (ASTN2), indicating novel genetic influences that influence hippocampal size and possibly the risk of cognitive decline and dementia ging Gene-Environment Susceptibility-Reykjavik Study: The research has been funded by NIA contract N01- AG-12100 with contributions from NEI, NIDCD and NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The Atherosclerosis Risk in Communities Study: The research is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694 and R01HL7825; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. This project was also supported by grant HL093029 (M.F.). The Cardiovascular Health Study: co-authors were supported in part by NHLBI grants HL087652 and HL105756 (J.C.B., W.L.) as well as NIA grant AG20098 and AG05133 (J.T.B.). The Austrian Stroke Prevention Study: The research reported in this article was funded by the Austrian Science Fond (FWF) grant number P20545-P05 and P13180. The Medical University of Graz supports the databank of the ASPS. The authors thank the staff and the participants of the ASPS for their valuable contributions. We thank Birgit Reinhart for her long-term administrative commitment and Ing Johann Semmler for the technical assistance at creating the DNA-bank. Erasmus Rucphen Family Study: This study is financially supported by the Netherlands Organization for Scientific Research (NWO), the Internationale Stichting Alzheimer Onderzoek (ISAO), the Hersenstichting Nederland (HSN), and the Centre for Medical Systems Biology (CMSB *1 and 2*) in the framework of the Netherlands Genomics Initiative (NGI). We thank the participants from the Genetic Research in Isolated Populations, Erasmus Rucphen Family, who made this work possible. Framingham Heart Study: From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. This work was supported by the National Heart, Lung and Blood Institute?s Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This study was also supported by grants from the National Institute of Neurological Disorders and Stroke (NS17950) and the National Institute of Aging (AG08122, AG16495, AG033193, AG031287). The Religious Order Study (ROS) and Rush Memory and Aging Project (R-MAP): The R-MAP and ROS data used in this article was supported by National Institute on Aging grants P30AG10161, R01AG17917, and R01AG15819, the Illinois Department of Public Health, the Rush Clinical Translational Science Consortium, and a gift from Ms. Marsha Dowd. The Rotterdam Study: The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their Bis et al. Page 9 Nat Genet . Author manuscript; available in PMC 2012 November 01. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript help in creating the GWAS database, and Karol Estrada and Maksim V. Struchalin for their support in creation and analysis of imputed data. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The Rotterdam Scan Study is supported by the Netherlands Organization of Scientific Research (NWO) project nrs. 918-46-615; 904-61-096; 904-61-133; 948-00-010; and Nederlandse Hartstichting 2009B102; and Internationaal Parkinson Fonds. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The Tasmanian Study of Gait and Cognition (TASCOG) is supported by Project Grants from the National Health and Medical Research Council (NHMRC IDs 403000, 491109, 606543), and a grant from the Wicking Dementia Education and Research Centre, Hobart. Velandai Srikanth is supported by an NHMRC/National Heart Foundation Career Development Fellowship (ID 606544). Matthew Brown is supported by an NHMRC Principal Research Fellowship. Three City Study (3C): We thank the staff and the participants of the 3C Study for their important contributions. The 3C Study is conducted under a partnership agreement between the Institut National de la Sante et de la Recherche Medicale (INSERM), the Victor Segalen?Bordeaux II University, and Sanofi-Aventis. The Fondation pour la Recherche Medicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, Mutuelle Generale de l?Education Nationale (MGEN), Institut de la Longevite, Conseils Regionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research?INSERM Programme ?Cohortes et collections de donnees biologiques.? Lille Genopole received an unconditional grant from Eisai. We thank A. Boland (Centre National de Genotypage) for her technical help in preparing the DNA samples for analyses. This work was supported by the National Foundation for Alzheimer?s Disease and Related Disorders, the Institut Pasteur de Lille and the Centre National de Genotypage.
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Aiden Peter Corvin, Gary (James) Donohoe

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Aiden Corvin
Trinity College Dublin
Total Publications: 199
Gary Donohoe
Trinity College Dublin
Total Publications: 143