publication . Preprint . Other literature type . Research . 2019

Common variants in Alzheimer's disease: Novel association of six genetic variants with AD and risk stratification by polygenic risk scores

Raquel Huerto; Miquel Baquero; Rick Tankard; Alberto Lleó; Iris E. Jansen; Joshua C. Bis; Benjamin Grenier-Boley; Jordi Pérez-Tur; Pablo García; Niccolò Tesi; ...
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Open Access English
  • Published: 15 Nov 2019
  • Publisher: Cold Spring Harbor Laboratory
  • Country: Switzerland
Abstract
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>BACKGROUND</jats:title><jats:p>Disentangling the genetic constellation underlying Alzheimer’s disease (AD) is important. Doing so allows us to identify biological pathways underlying AD, point towards novel drug targets and use the variants for individualised risk predictions in disease modifying or prevention trials. In the present work we report on the largest genome-wide association study (GWAS) for AD risk to date and show the combined utility of proven AD loci for precision medicine using polygenic risk scores (PRS).</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>Three sets of summ...
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doi: 10.1101/19012021 , 10.5167/uzh-179831
Subjects
free text keywords: Department of Child and Adolescent Psychiatry, 610 Medicine & health, Disease, Genomics, Heterozygote advantage, Genotype, Locus (genetics), Missense mutation, Genome-wide association study, Apolipoprotein E, Oncology, medicine.medical_specialty, medicine, Internal medicine, business.industry, business
Related Organizations
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Funded by
EC| MOPEAD
Project
MOPEAD
Models Of Patient Engagement for Alzheimer’s Disease - Sofia ref.: 115985
  • Funder: European Commission (EC)
  • Project Code: 115985
  • Funding stream: H2020 | IMI2-RIA
, NIH| CHARGE consortium: gene discovery for CVD and aging phenotypes
Project
CHARGE consortium: gene discovery for CVD and aging phenotypes
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2R01HL105756-07
  • Funding stream: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
, EC| ADAPTED
Project
ADAPTED
Alzheimers Disease Apolipoprotein Pathology for Treatment Elucidation and Development - Sofia ref.: 115975
  • Funder: European Commission (EC)
  • Project Code: 115975
  • Funding stream: H2020 | IMI2-RIA
, NIH| AGES STUDY-THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENNIUM-260012100
Project
AGES STUDY-THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENNIUM-260012100
  • Funder: National Institutes of Health (NIH)
  • Project Code: N01AG012100-017
  • Funding stream: NATIONAL INSTITUTE ON AGING
, NIH| National Cell Repository for Alzheimers Disease
Project
National Cell Repository for Alzheimers Disease
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U24AG021886-09
  • Funding stream: NATIONAL INSTITUTE ON AGING
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Preprint . 2019
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Zurich Open Repository and Archive
Research . 2019
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https://www.medrxiv.org/conten...
Preprint
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Figure 3. Clinical impact of a Polygenic Risk Score for Alzheimer's Disease............................................4 0.277 Protective 0.92[0.90-0.93] 0.379 Protective 0.91[0.90-0.93] 0.332 Protective 1.12[1.10-1.14] 0.033 Protective 0.83[0.79-0.87] 0.228 Protective 1.08[1.06-1.10] Rogaeva et al. 2007 0.168 Risk 3.00[2.93-3.07] 0.00E+00 Strittmatter et al. 1993 Strittmatter et al. 1993 0.049 Protective 1.58[1.52-1.65] 3.20E-123 0.290 Protective 1.06[1.04-1.08] 3.11E-08 Table 2. The genetic landscape of late-onset Alzheimer's Disease Note: Association results of overall meta-GWAS cohorts. Effect allele: A1. Allelic Freq. is from A1 in GR@ACE discovery dataset. LOF: Loss-of-function.

0.95[0.92-0.97] 1.08E-04 1.06[1.04-1.08] 5.51E-10 Marioni et al. 2018 Alvarez et al. 1999 0.92[0.90-0.94] 8.42E-16 Present work Sims et al. 2017 Marioni et al. 2018 Hollinworth et al. 2011

Related research
Abstract
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>BACKGROUND</jats:title><jats:p>Disentangling the genetic constellation underlying Alzheimer’s disease (AD) is important. Doing so allows us to identify biological pathways underlying AD, point towards novel drug targets and use the variants for individualised risk predictions in disease modifying or prevention trials. In the present work we report on the largest genome-wide association study (GWAS) for AD risk to date and show the combined utility of proven AD loci for precision medicine using polygenic risk scores (PRS).</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>Three sets of summ...
Read more
doi: 10.1101/19012021 , 10.5167/uzh-179831
Subjects
free text keywords: Department of Child and Adolescent Psychiatry, 610 Medicine & health, Disease, Genomics, Heterozygote advantage, Genotype, Locus (genetics), Missense mutation, Genome-wide association study, Apolipoprotein E, Oncology, medicine.medical_specialty, medicine, Internal medicine, business.industry, business
Related Organizations
View more
Funded by
EC| MOPEAD
Project
MOPEAD
Models Of Patient Engagement for Alzheimer’s Disease - Sofia ref.: 115985
  • Funder: European Commission (EC)
  • Project Code: 115985
  • Funding stream: H2020 | IMI2-RIA
, NIH| CHARGE consortium: gene discovery for CVD and aging phenotypes
Project
CHARGE consortium: gene discovery for CVD and aging phenotypes
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2R01HL105756-07
  • Funding stream: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
, EC| ADAPTED
Project
ADAPTED
Alzheimers Disease Apolipoprotein Pathology for Treatment Elucidation and Development - Sofia ref.: 115975
  • Funder: European Commission (EC)
  • Project Code: 115975
  • Funding stream: H2020 | IMI2-RIA
, NIH| AGES STUDY-THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENNIUM-260012100
Project
AGES STUDY-THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENNIUM-260012100
  • Funder: National Institutes of Health (NIH)
  • Project Code: N01AG012100-017
  • Funding stream: NATIONAL INSTITUTE ON AGING
, NIH| National Cell Repository for Alzheimers Disease
Project
National Cell Repository for Alzheimers Disease
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U24AG021886-09
  • Funding stream: NATIONAL INSTITUTE ON AGING
View more
Download fromView all 5 versions
medRxiv
Preprint . 2019
Provider: medRxiv
https://www.medrxiv.org/conten...
Preprint
Provider: UnpayWall
Zurich Open Repository and Archive
Research . 2019
Provider: Zurich Open Repository and Archive
https://www.medrxiv.org/conten...
Preprint
Provider: Microsoft Academic Graph
View more

Figure 3. Clinical impact of a Polygenic Risk Score for Alzheimer's Disease............................................4 0.277 Protective 0.92[0.90-0.93] 0.379 Protective 0.91[0.90-0.93] 0.332 Protective 1.12[1.10-1.14] 0.033 Protective 0.83[0.79-0.87] 0.228 Protective 1.08[1.06-1.10] Rogaeva et al. 2007 0.168 Risk 3.00[2.93-3.07] 0.00E+00 Strittmatter et al. 1993 Strittmatter et al. 1993 0.049 Protective 1.58[1.52-1.65] 3.20E-123 0.290 Protective 1.06[1.04-1.08] 3.11E-08 Table 2. The genetic landscape of late-onset Alzheimer's Disease Note: Association results of overall meta-GWAS cohorts. Effect allele: A1. Allelic Freq. is from A1 in GR@ACE discovery dataset. LOF: Loss-of-function.

0.95[0.92-0.97] 1.08E-04 1.06[1.04-1.08] 5.51E-10 Marioni et al. 2018 Alvarez et al. 1999 0.92[0.90-0.94] 8.42E-16 Present work Sims et al. 2017 Marioni et al. 2018 Hollinworth et al. 2011

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