publication . Article . 2016

Integration of bioinformatics and imaging informatics for identifying rare PSEN1 variants in Alzheimer’s disease

Nho, Kwangsik; Horgusluoglu, Emrin; Kim, Sungeun; Risacher, Shannon L.; Kim, Dokyoon; Foroud, Tatiana; Aisen, Paul S.; Petersen, Ronald C.; Jack, Clifford R.; Shaw, Leslie M.; ...
Open Access English
  • Published: 01 Aug 2016 Journal: BMC Medical Genomics, volume 9, issue Suppl 1 (eissn: 1755-8794, Copyright policy)
  • Publisher: BioMed Central
  • Country: United States
Abstract
Background: Pathogenic mutations in PSEN1 are known to cause familial early-onset Alzheimer’s disease (EOAD) but common variants in PSEN1 have not been found to strongly influence late-onset AD (LOAD). The association of rare variants in PSEN1 with LOAD-related endophenotypes has received little attention. In this study, we performed a rare variant association analysis of PSEN1 with quantitative biomarkers of LOAD using whole genome sequencing (WGS) by integrating bioinformatics and imaging informatics. Methods: A WGS data set (N = 815) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort was used in this analysis. 757 non-Hispanic Caucasian partic...
Subjects
free text keywords: Research, Whole genome sequencing, Imaging genetics, Gene-based association of rare variants, PSEN1, Genetics(clinical), Genetics
Funded by
CIHR
Project
  • Funder: Canadian Institutes of Health Research (CIHR)
,
NIH| National Cell Repository for Alzheimers Disease
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U24AG021886-09
  • Funding stream: NATIONAL INSTITUTE ON AGING
,
NIH| Integration of Bio-, Medical, and Imaging Informatics for Complex Diseases
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 4R00LM011384-02
  • Funding stream: NATIONAL LIBRARY OF MEDICINE
,
NIH| Alzheimers Disease Neuroimaging Initiative
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1U01AG024904-01
  • Funding stream: NATIONAL INSTITUTE ON AGING
,
NIH| CORE-- EDUCATION AND INFORMATION TRANSFER
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5P30AG010133-08
  • Funding stream: NATIONAL INSTITUTE ON AGING
33 references, page 1 of 3

Ridge, PG, Mukherjee, S, Crane, PK, Kauwe, JS, Alzheimer’s Disease Genetics, C. Alzheimer’s disease: analyzing the missing heritability. PLoS ONE. 2013; 8: e79771 [OpenAIRE] [PubMed] [DOI]

Gatz, M, Pedersen, NL, Berg, S, Johansson, B, Johansson, K. Heritability for Alzheimer’s disease: the study of dementia in Swedish twins. J Gerontol A Biol Sci Med Sci. 1997; 52: M117-M125 [OpenAIRE] [PubMed] [DOI]

Lambert, JC, Ibrahim-Verbaas, CA, Harold, D, Naj, AC, Sims, R. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet. 2013; 45: 1452-1458 [OpenAIRE] [PubMed] [DOI]

Esteban-Jurado, C, Vila-Casadesus, M, Garre, P, Lozano, JJ, Pristoupilova, A. Whole-exome sequencing identifies rare pathogenic variants in new predisposition genes for familial colorectal cancer. Genet Med. 2015; 17: 131-142 [OpenAIRE] [PubMed] [DOI]

van Dijk, EL, Auger, H, Jaszczyszyn, Y, Thermes, C. Ten years of next-generation sequencing technology. Trends Genet. 2014; 30: 418-426 [OpenAIRE] [PubMed] [DOI]

Cirulli, ET, Goldstein, DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet. 2010; 11: 415-425 [OpenAIRE] [PubMed] [DOI]

Guerreiro, R, Hardy, J. TREM2 and neurodegenerative disease. N Engl J Med. 2013; 369: 1569-1570 [PubMed]

Guerreiro, RJ, Lohmann, E, Bras, JM, Gibbs, JR, Rohrer, JD. Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol. 2013; 70: 78-84 [OpenAIRE] [PubMed] [DOI]

Guerreiro, R, Wojtas, A, Bras, J, Carrasquillo, M, Rogaeva, E. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013; 368: 117-127 [OpenAIRE] [PubMed] [DOI]

Steinberg, S, Stefansson, H, Jonsson, T, Johannsdottir, H, Ingason, A. Loss-of-function variants in ABCA7 confer risk of Alzheimer’s disease. Nat Genet. 2015; 47: 445-447 [OpenAIRE] [PubMed] [DOI]

Cruchaga, C, Karch, CM, Jin, SC, Benitez, BA, Cai, Y. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease. Nature. 2014; 505: 550-554 [OpenAIRE] [PubMed] [DOI]

Benitez, BA, Karch, CM, Cai, Y, Jin, SC, Cooper, B. The PSEN1, p. E318G variant increases the risk of Alzheimer’s disease in APOE-epsilon4 carriers. PLoS Genet. 2013; 9: e1003685 [OpenAIRE] [PubMed] [DOI]

Singleton, A, Hardy, J. A generalizable hypothesis for the genetic architecture of disease: pleomorphic risk loci. Hum Mol Genet. 2011; 20: R158-R162 [OpenAIRE] [PubMed] [DOI]

Medland, SE, Jahanshad, N, Neale, BM, Thompson, PM. Whole-genome analyses of whole-brain data: working within an expanded search space. Nat Neurosci. 2014; 17: 791-800 [OpenAIRE] [PubMed] [DOI]

Saykin, AJ, Shen, L, Foroud, TM, Potkin, SG, Swaminathan, S. Alzheimer’s Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans. Alzheimers Dement. 2010; 6: 265-273 [OpenAIRE] [PubMed] [DOI]

33 references, page 1 of 3
Abstract
Background: Pathogenic mutations in PSEN1 are known to cause familial early-onset Alzheimer’s disease (EOAD) but common variants in PSEN1 have not been found to strongly influence late-onset AD (LOAD). The association of rare variants in PSEN1 with LOAD-related endophenotypes has received little attention. In this study, we performed a rare variant association analysis of PSEN1 with quantitative biomarkers of LOAD using whole genome sequencing (WGS) by integrating bioinformatics and imaging informatics. Methods: A WGS data set (N = 815) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort was used in this analysis. 757 non-Hispanic Caucasian partic...
Subjects
free text keywords: Research, Whole genome sequencing, Imaging genetics, Gene-based association of rare variants, PSEN1, Genetics(clinical), Genetics
Funded by
CIHR
Project
  • Funder: Canadian Institutes of Health Research (CIHR)
,
NIH| National Cell Repository for Alzheimers Disease
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U24AG021886-09
  • Funding stream: NATIONAL INSTITUTE ON AGING
,
NIH| Integration of Bio-, Medical, and Imaging Informatics for Complex Diseases
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 4R00LM011384-02
  • Funding stream: NATIONAL LIBRARY OF MEDICINE
,
NIH| Alzheimers Disease Neuroimaging Initiative
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1U01AG024904-01
  • Funding stream: NATIONAL INSTITUTE ON AGING
,
NIH| CORE-- EDUCATION AND INFORMATION TRANSFER
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5P30AG010133-08
  • Funding stream: NATIONAL INSTITUTE ON AGING
33 references, page 1 of 3

Ridge, PG, Mukherjee, S, Crane, PK, Kauwe, JS, Alzheimer’s Disease Genetics, C. Alzheimer’s disease: analyzing the missing heritability. PLoS ONE. 2013; 8: e79771 [OpenAIRE] [PubMed] [DOI]

Gatz, M, Pedersen, NL, Berg, S, Johansson, B, Johansson, K. Heritability for Alzheimer’s disease: the study of dementia in Swedish twins. J Gerontol A Biol Sci Med Sci. 1997; 52: M117-M125 [OpenAIRE] [PubMed] [DOI]

Lambert, JC, Ibrahim-Verbaas, CA, Harold, D, Naj, AC, Sims, R. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet. 2013; 45: 1452-1458 [OpenAIRE] [PubMed] [DOI]

Esteban-Jurado, C, Vila-Casadesus, M, Garre, P, Lozano, JJ, Pristoupilova, A. Whole-exome sequencing identifies rare pathogenic variants in new predisposition genes for familial colorectal cancer. Genet Med. 2015; 17: 131-142 [OpenAIRE] [PubMed] [DOI]

van Dijk, EL, Auger, H, Jaszczyszyn, Y, Thermes, C. Ten years of next-generation sequencing technology. Trends Genet. 2014; 30: 418-426 [OpenAIRE] [PubMed] [DOI]

Cirulli, ET, Goldstein, DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet. 2010; 11: 415-425 [OpenAIRE] [PubMed] [DOI]

Guerreiro, R, Hardy, J. TREM2 and neurodegenerative disease. N Engl J Med. 2013; 369: 1569-1570 [PubMed]

Guerreiro, RJ, Lohmann, E, Bras, JM, Gibbs, JR, Rohrer, JD. Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol. 2013; 70: 78-84 [OpenAIRE] [PubMed] [DOI]

Guerreiro, R, Wojtas, A, Bras, J, Carrasquillo, M, Rogaeva, E. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013; 368: 117-127 [OpenAIRE] [PubMed] [DOI]

Steinberg, S, Stefansson, H, Jonsson, T, Johannsdottir, H, Ingason, A. Loss-of-function variants in ABCA7 confer risk of Alzheimer’s disease. Nat Genet. 2015; 47: 445-447 [OpenAIRE] [PubMed] [DOI]

Cruchaga, C, Karch, CM, Jin, SC, Benitez, BA, Cai, Y. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease. Nature. 2014; 505: 550-554 [OpenAIRE] [PubMed] [DOI]

Benitez, BA, Karch, CM, Cai, Y, Jin, SC, Cooper, B. The PSEN1, p. E318G variant increases the risk of Alzheimer’s disease in APOE-epsilon4 carriers. PLoS Genet. 2013; 9: e1003685 [OpenAIRE] [PubMed] [DOI]

Singleton, A, Hardy, J. A generalizable hypothesis for the genetic architecture of disease: pleomorphic risk loci. Hum Mol Genet. 2011; 20: R158-R162 [OpenAIRE] [PubMed] [DOI]

Medland, SE, Jahanshad, N, Neale, BM, Thompson, PM. Whole-genome analyses of whole-brain data: working within an expanded search space. Nat Neurosci. 2014; 17: 791-800 [OpenAIRE] [PubMed] [DOI]

Saykin, AJ, Shen, L, Foroud, TM, Potkin, SG, Swaminathan, S. Alzheimer’s Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans. Alzheimers Dement. 2010; 6: 265-273 [OpenAIRE] [PubMed] [DOI]

33 references, page 1 of 3
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