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January 01, 2013; 80 (1) Article

Fat mass and obesity gene and cognitive decline

The Atherosclerosis Risk in Communities Study

Jan Bressler, Myriam Fornage, Ellen W. Demerath, David S. Knopman, Keri L. Monda, Kari E. North, Alan Penman, Thomas H. Mosley, Eric Boerwinkle
First published November 7, 2012, DOI: https://doi.org/10.1212/WNL.0b013e3182768910
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Article Information

vol. 80 no. 1 92-99
DOI: 
https://doi.org/10.1212/WNL.0b013e3182768910
PubMed: 
23136261
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received February 5, 2012
  • Accepted August 15, 2012
  • First Published November 7, 2012.

Article Versions

Copyright & Usage: 
© 2012 American Academy of Neurology

Author Disclosures

    1. Jan Bressler, PhD,
    2. Myriam Fornage, PhD,
    3. Ellen W. Demerath, PhD,
    4. David S. Knopman, MD,
    5. Keri L. Monda, PhD,
    6. Kari E. North, PhD,
    7. Alan Penman, PhD,
    8. Thomas H. Mosley, PhD and
    9. Eric Boerwinkle, PhD
  1. Jan Bressler, PhD,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Dr. Michael Andreeff (spouse) received funding for travel from Roche Pharmaceuticals; and an honorarium from Genzyme.

    Editorial Boards:

    1. Spouse serves on the editorial board of Annals of Hematology (1995-present); Leukemia (2008-present); and Molecular Cancer Therapeutics (2012).

    Patents:

    1. Spouse holds a patent for a drug used in cancer treatment from Reata Pharmaceuticals.

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Spouse receives consulting fees from Reata Pharmaceuticals (2004-present).

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Spouse received an unrestricted gift for research from Karyopharm (2011).

    Research Support, Government Entities:

    1. Funded as co-investigator by NIH grant U01 HL096917 (2010-2012); Spouse is funded by NIH grants P01 CA55164 (2007-present); and R21 CA143805 (2010-present) as principal investigator; by NIH grants RC1 CA146381 (2009-present) and P50 CA12700 (2008-present) as co-investigator; by NIH grants P01 CA049639 (2010-present); P50 CA100632 (2008-present); P50 CA083639 (2010-present); and P50 CA136411 (2009-present) as project leader; by NIH grant P30 CA0166672 (2008-present) as core leader; and by FDA grant R01 FD003733 (2009-present) as principal investigator

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. Spouse received license fee payments for drug used in cancer treatment from Reata Pharmaceuticals.

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Myriam Fornage, PhD,
    3. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Ellen W. Demerath, PhD,
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. COSMED, INC

    Research Support, Government Entities:

    1. NIH, N01 HC55019, Co-I, 2010-2016, NIH, DK053685, PI, 2007-2012, NIH, N01 HV048048, Co-I, 2008-2013, NIH, R01 HD012252 (Subcontract PI) 2010-2016, NIH, U01 HL103621, Co-I, 2010 - 2017

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. David S. Knopman, MD,
    5. Scientific Advisory Boards:

    1. Lilly Pharmaceuticals, Data Safety Monitoring Board

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. (1) Lecture, University of Zurich, March 2010; (2) Lecture, University of Montana, October 2010; (3) Lecture, University of Toronto, March 2012

    Editorial Boards:

    1. Neurology, Deputy Editor

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Janssen Alzheimer Immunotherapy program 3/29/11: honorarium paid to my institution; (2) Merck Alzheimer program 11/5/11 paid to my institution.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Janssen for Alzheimer clinical trial, (2) Forest Laboratories for clinical trial in FTLD with memantine, (3) Baxter Laboratories for Alzheimer Clinical trial

    Research Support, Government Entities:

    1. NIH: R01-AG11378 ongoing, P50-AG 16574 (Mayo Alzheimer's Disease Research Center) ongoing, U01 AG 06786 (Mayo Alzheimer Disease Patient Registry) ongoing. NIH R01 AG32306 FTD Neuro-imaging;Initiative. 1U01HL096917-01 ARIC Dementia Study.AG 037551 Chronic Kidney Disease and Cognitive functioning.

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Keri L. Monda, PhD,
    6. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH, Research Assistant Professor salary, 2011

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Kari E. North, PhD,
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Guest Editor for Circulation, Editor for Frontiers Genetic Epidemiology

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Alan Penman, PhD,
    8. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. 1. NIH/NHLBI N01-HC55021 - Mosley (PI) 02/01/2006 - 11/14/2016, Atherosclerosis Risk in Communities Study (ARIC), Role: Biostatistician (Jackson Field Center), 2. NIH/NHLBI/NINDS/NEI U01-HL096917 (Mosley) 07/07/2010 - 04/30/2014, ARIC Neurocognitive Study (ARIC NCS), Role: Biostatistician (Jackson Field Center), 3. UMC/VA CLIN-001-10F - Burton (PI) 01/01/2012 - 06/30/2014, Interaction of HSV-2 in Veterans with Chronic Hepatitis C Co-Infection, Role: Biostatistician

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. UMMC #58741 - Sobrin (PI) 10/01/2010-09/30/2013, Friends of the Massachusetts Eye and Ear Infirmary Genetics of Proliferative Diabetic Retinopathy in African-Americans, Role: Jackson PI

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  8. Thomas H. Mosley, PhD and
    9. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  9. Eric Boerwinkle, PhD
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. Boerwinkle: ACTIVE 5 RC2 HL 102419-02 (Boerwinkle) 09/30/2009 - 07/31/2012, 1.20 calendar NIH/NHLBI $13,687,235 Building on GWAS for NHLBI-diseases: the CHARGE Consortium This project is to re-sequence selected regions identified in GWAS of major CVD traits. 5 N01HC 55016-40-0-1 (Ballantyne) 11/15/2010 - 10/31/16, 0.60 calendar NIH/NHLBI $$384,834 Atherosclerosis Risk in Communities (ARIC) Study This project will carry-out analyze and publish targeted genetic and gene-environment interaction studies on coronary heart disease, congestive heart failure, endothelial function and lung function and provide expert guidance and leadership to the ARIC Steering Committee on technical, analytical and ethical issues related to large scale genomic research. 5 U01 HG 004803-04 (Heiss) 07/17/2008 - 05/31/2013, 0.36 calendar NIH/NHGRI-University of North Carolina, Chapel Hill $348,258 Genetic Epidemiology of Causal Variants Across the Life Course To accelerate the understanding of the role and population impact of putative causal genetic variants related to complex diseases. 5 RC2 HG005697 (Hixson) 09/30/2009 - 08/31/2012 0.60 calendar NIH/NHLBI Next-Generation Medical Resequencing of Gout Disease Genes in the ARIC Cohort This project will use next-generation sequencing technology to resequence candidate genes in gout cases and controls from the ARIC cohort to identify genetic variants that influence gout and uric acid levels.5 R01 HL 072810-09 (Boerwinkle) 06/01/2003 - 02/28/2013 1.20 calendar NIH/NHLBI $694,917 Modeling DNA Diversity in Reverse Cholesterol Transport The goal of this Multi-Institutional Research Project grant is to identify the genes influencing HDL-C in the population-at-large. This research not only considers the individual effects of variation in each gene, but their interactions with other genes and with the environment. We also ask if these genetic variations predict CHD beyond the traditional risk factors, such as smoking and hypertension. 1 U01 HL 096917-02 (Mosley) 07/07/2010 - 06/30/2013 0.60 calendar NIH/NHLBI/NINDS/NEI $244,613ARIC Neurocognitive Study (ARIC NCS) ARIC NCS will identify risk factors for dementia, mild cognitive impairment, and cognitive decline in the biracial longitudinal ARIC cohort study of the natural history of atherosclerosis. 1 R01 HL 106034-02 (Xiong) 01/10/2011 - 12/31/2014 0.60 calendar NIH/NHLBI $376,093 Statistical Methods for Finding Missing Heritability The goal of this proposal is to use genome continuum model as a general principle, data reduction, functional data analysis techniques, and systems biology tools for developing novel and powerful statistical methods for detection interaction between genes (or pathways) with both common and rare variants and environments with both discrete and continuous measurements, and carry out genome-wide gene-environment interaction. 2 U01 GM 074492-08 (Johnson) 08/03/2005 - 07/31/2015 0.6 calendar NIH/NIGMS $337,485Pharmacogenomic Evaluation of Antihypertensive Responses We will provide genetic analysis of all study samples for the genome spanning studies. 1 U54 HG006542-01 (Valle) 12/05/11 - 11/30/15 0.6 calendar NIH Baylor-Johns Hopkins Center for Mendelian Genetics Collaboration with Drs. Valle and Lupski to identify genes leading to targeted Mendelian disorders. Analyzing data to establish genotype-phenotype associations which will also include formal statistical analyses of clustering of variants within a gene or gene region. 2 U54 HG003273-09 (Gibbs) 11/01/11 - 10/31/2012 2.4 calendar NIH $235,162 The Human Genome Sequencing Center Active close collaboration on the statistical design and analysis of projects, particular population studies.Vicki Huff (Spouse): U10 CA09843-07S6 Huff (Co-PI) 09/01/2009- 08/31/2012 NIH/NCI $20,839 annual direct costs TARGET: Wilms Tumor, P. Adamson, PI 0.6 months The major goal of this project is to use genomic data to identify genes/pathways that can be therapeutically targeted in Wilms tumor patients RP100329 Huff (PI) 3/1/2010 - 2/28/2013 CPRIT (Cancer Prevention & Research Institute of Texas) $186,104 annual direct costs Next Generation Genomic Sequence Identification of the 19q 1.8 months Familial Wilms Tumor Predisposition Gene The major goal of this project is to identify the 19q familial WT gene using Next-Gen DNA sequencing data. RP110324 Huff (PI) 1/1/2011 - 12/31/2014 CPRIT (Cancer Prevention & Research Institute of Texas) $351,165 annual direct costs Impact of differentiation status on tumorigenesis 3.6 months The major goal of this project is to determine whether targeting gene alterations to different cellular compartments in the developing kidney will result in Wilms tumors that exhibit distinctive molecular and clinical characteristics. CA98543 09 Huff (Chair, COG Renal Tumor Biol Comm) 3/1/2012 - 2/28/2013 NIH/NCI Children's Oncology Group (COG). P. Adamson, PI $5,017 annual direct costs 0.3 months The goal of this project is to develop more efficacious therapies for Wilms tumor patients. My role is to head up the Renal Tumor Biology Committee that oversees and guides research projects that provide biological data to further this goal. CA016672 DePinho (PI) 9/14/1998 - 6/30/2013 NIH/NCI Huff, Director $283,568 annual direct costs Cancer Center Support Grant-Sequence & Microarray Facility 1.2 months The goal of this project is to provide MDACC investigators with state-of-the-art technology for DNA and RNA analyses. CA054498 Huff, PI, Subcontract 9/1/2012 - 8/31/2017 NIH/NCI Breslow (PI) $14,882 annual direct costs Late Effects of Treatment in Wilms Tumor Survivors 0.3 months The goal of this project is to assess the long-term consequences of treatment in survivors of WIlms tumor, with special reference to the role of germline WT1 mutations.

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Human Genetics Center (J.B., M.F., E.B.), School of Public Health, University of Texas Health Science Center at Houston; Brown Foundation Institute of Molecular Medicine (M.F., E.B.), University of Texas Health Science Center at Houston; Division of Epidemiology and Community Health (E.W.D.), School of Public Health, University of Minnesota, Minneapolis; Department of Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (K.L.M., K.E.N.), Gillings School of Global Public Health, University of North Carolina, Chapel Hill; Carolina Center for Genome Sciences (K.E.N.), School of Medicine, University of North Carolina, Chapel Hill; and Department of Internal Medicine (A.P., T.H.M.), Division of Geriatrics, University of Mississippi Medical Center, Jackson.
  1. Correspondence to Eric Boerwinkle: Eric.Boerwinkle{at}uth.tmc.edu
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