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Genome-wide Screen Identifies rs646776 near Sortilin as a Regulator of Progranulin Levels in Human Plasma

Carrasquillo, Minerva M., Nicholson, Alexandra M., Finch, NiCole, Gibbs, J. Raphael, Baker, Matt, Rutherford, Nicola J., Hunter, Talisha A., DeJesus-Hernandez, Mariely, Bisceglio, Gina D., Mackenzie, Ian R., Singleton, Andrew, Cookson, Mark R., Crook, Julia E., Dillman, Allissa, Hernandez, Dena, Petersen, Ronald C., Graff-Radford, Neill R., Younkin, Steven G., Rademakers, Rosa·2010·The American Journal of Human Genetics
DOI 10.1016/j.ajhg.2010.11.002
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Abstract

Recent studies suggest progranulin (GRN) is a neurotrophic factor. Loss-of-function mutations in the progranulin gene (GRN) cause frontotemporal lobar degeneration (FTLD), a progressive neurodegenerative disease affecting ∼10% of early-onset dementia patients. Using an enzyme-linked immunosorbent assay, we previously showed that GRN is detectable in human plasma and can be used to predict GRN mutation status. This study also showed a wide range in plasma GRN levels in non-GRN mutation carriers, including controls. We have now performed a genome-wide association study of 313,504 single-nucleotide polymorphisms (SNPs) in 533 control samples and identified on chromosome 1p13.3 two SNPs with genome-wide significant association with plasma GRN levels (top SNP rs646776; p = 1.7 × 10⁻³⁰). The association of rs646776 with plasma GRN levels was replicated in two independent series of 508 controls (p = 1.9 × 10⁻¹⁹) and 197 FTLD patients (p = 6.4 × 10⁻¹²). Overall, each copy of the minor C allele decreased GRN levels by ∼15%. SNP rs646776 is located near sortilin (SORT1), and the minor C allele of rs646776 was previously associated with increased SORT1 mRNA levels. Supporting these findings, overexpression of SORT1 in cultured HeLa cells dramatically reduced GRN levels in the conditioned media, whereas knockdown of SORT1 increased extracellular GRN levels. In summary, we identified significant association of a locus on chromosome 1p13.3 with plasma GRN levels through an unbiased genome-…

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Research works printed but not linked: 38

  1. Bateman, 2009, The granulin gene family: From cancer to dementia, Bioessays, 31, 1245, 10.1002/bies.200900086 · DOI
  2. Cruts, 2006, Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21, Nature, 442, 920, 10.1038/nature05017 · DOI · Paper page
  3. Graff-Radford, 2007, Frontotemporal dementia, Semin. Neurol., 27, 48, 10.1055/s-2006-956755 · DOI
  4. Mendez, 2009, Frontotemporal dementia: Therapeutic interventions, Front Neurol. Neurosci., 24, 168, 10.1159/000197896 · DOI
  5. Gijselinck, 2008, Granulin mutations associated with frontotemporal lobar degeneration and related disorders: An update, Hum. Mutat., 29, 1373, 10.1002/humu.20785 · DOI
  6. Ahmed, 2010, Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggest a role for progranulin in successful aging, Am. J. Pathol., 177, 311, 10.2353/ajpath.2010.090915 · DOI
  7. Ryan, 2009, Progranulin is expressed within motor neurons and promotes neuronal cell survival, BMC Neurosci., 10, 130, 10.1186/1471-2202-10-130 · DOI
  8. Van Damme, 2008, Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival, J. Cell Biol., 181, 37, 10.1083/jcb.200712039 · DOI
  9. Yin, 2010, Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice, J. Exp. Med., 207, 117, 10.1084/jem.20091568 · DOI · Paper page
  10. Brouwers, 2008, Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer disease, Neurology, 71, 656, 10.1212/01.wnl.0000319688.89790.7a · DOI
  11. Sleegers, 2008, Progranulin genetic variability contributes to amyotrophic lateral sclerosis, Neurology, 71, 253, 10.1212/01.wnl.0000289191.54852.75 · DOI · Paper page
  12. Nuytemans, 2008, Progranulin variability has no major role in Parkinson disease genetic etiology, Neurology, 71, 1147, 10.1212/01.wnl.0000327563.10320.2b · DOI
  13. Viswanathan, 2009, An association study between granulin gene polymorphisms and Alzheimer's disease in Finnish population, Am. J. Med. Genet. B. Neuropsychiatr. Genet., 150B, 747, 10.1002/ajmg.b.30889 · DOI
  14. Rademakers, 2009, Recent insights into the molecular genetics of dementia, Trends Neurosci., 32, 451, 10.1016/j.tins.2009.05.005 · DOI
  15. Finch, 2009, Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members, Brain, 132, 583, 10.1093/brain/awn352 · DOI
  16. Ghidoni, 2008, Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration, Neurology, 71, 1235, 10.1212/01.wnl.0000325058.10218.fc · DOI
  17. Schofield, 2010, Low serum progranulin predicts the presence of mutations: A prospective study, J. Alzheimers Dis., 10.3233/JAD-2010-101032 · DOI
  18. Sleegers, 2009, Serum biomarker for progranulin-associated frontotemporal lobar degeneration, Ann. Neurol., 65, 603, 10.1002/ana.21621 · DOI
  19. Carrasquillo, 2009, Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease, Nat. Genet., 41, 192, 10.1038/ng.305 · DOI · Paper page
  20. Kathiresan, 2008, Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans, Nat. Genet., 40, 189, 10.1038/ng.75 · DOI · Paper page
  21. Purcell, 2007, PLINK: A tool set for whole-genome association and population-based linkage analyses, Am. J. Hum. Genet., 81, 559, 10.1086/519795 · DOI · Paper page
  22. Jansen, 2007, Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury, Nat. Neurosci., 10, 1449, 10.1038/nn2000 · DOI · Paper page
  23. Hermey, 2009, The Vps10p-domain receptor family, Cell. Mol. Life Sci., 66, 2677, 10.1007/s00018-009-0043-1 · DOI
  24. Petersen, 1997, Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography, J. Biol. Chem., 272, 3599, 10.1074/jbc.272.6.3599 · DOI · Paper page
  25. Teng, 2005, ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin, J. Neurosci., 25, 5455, 10.1523/JNEUROSCI.5123-04.2005 · DOI · Paper page
  26. Mazella, 1998, The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor, J. Biol. Chem., 273, 26273, 10.1074/jbc.273.41.26273 · DOI
  27. Hu, 2010, Sortilin-mediated endocytosis determines levels of the frontotemporal dementia protein, progranulin, Neuron, 68, 654, 10.1016/j.neuron.2010.09.034 · DOI · Paper page
  28. Lu, 2010, Exploring genetic determinants of plasma total cholesterol levels and their predictive value in a longitudinal study, Atherosclerosis, 213, 200, 10.1016/j.atherosclerosis.2010.08.053 · DOI
  29. Muendlein, 2009, Significant impact of chromosomal locus 1p13.3 on serum LDL cholesterol and on angiographically characterized coronary atherosclerosis, Atherosclerosis, 206, 494, 10.1016/j.atherosclerosis.2009.02.040 · DOI · Paper page
  30. Ronald, 2009, Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease, Lipids Health Dis., 8, 52, 10.1186/1476-511X-8-52 · DOI
  31. Sandhu, 2008, LDL-cholesterol concentrations: a genome-wide association study, Lancet, 371, 483, 10.1016/S0140-6736(08)60208-1 · DOI
  32. Kleber, 2010, Association of the single nucleotide polymorphism rs599839 in the vicinity of the sortilin 1 gene with LDL and triglyceride metabolism, coronary heart disease and myocardial infarction. The Ludwigshafen Risk and Cardiovascular Health Study, Atherosclerosis, 209, 492, 10.1016/j.atherosclerosis.2009.09.068 · DOI
  33. Li, 2009, Genotype imputation, Annu. Rev. Genomics Hum. Genet., 10, 387, 10.1146/annurev.genom.9.081307.164242 · DOI · Paper page
  34. Li, 2006, Mach 1.0: Rapid haplotype reconstruction and missing genotype inference, Am. J. Hum. Genet., S79, 2290
  35. Barbosa-Morais, 2010, A re-annotation pipeline for Illumina BeadArrays: Improving the interpretation of gene expression data, Nucleic Acids Res., 38, e17, 10.1093/nar/gkp942 · DOI
  36. Sleegers, 2010, Role of progranulin as a biomarker for Alzheimer's disease, Biomark Med, 4, 37, 10.2217/bmm.09.82 · DOI
  37. Dimas, 2009, Common regulatory variation impacts gene expression in a cell type-dependent manner, Science, 325, 1246, 10.1126/science.1174148 · DOI
  38. Benjamini, 1995, Controlling the false discovery rate: a practical and powerful approach to multiple testing, J. R. Statist. Soc. B, 57, 289, 10.1111/j.2517-6161.1995.tb02031.x · DOI · Paper page

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Metadata

Authors
Carrasquillo, M. M., Nicholson, A. M., Finch, N., Gibbs, J. R., Baker, M., Rutherford, N. J., Hunter, T. A., DeJesus-Hernandez, M., Bisceglio, G. D., Mackenzie, I. R., Singleton, A., Cookson, M. R., Crook, J. E., Dillman, A., Hernandez, D., Petersen, R. C., Graff-Radford, N. R., Younkin, S. G., & Rademakers, R.
Venue
The American Journal of Human Genetics
Publisher
Elsevier BV
Published
2010-12
Volume
87
Issue
6
Pages
890-897
ISSN
0002-9297
DOI
10.1016/j.ajhg.2010.11.002
Cited by
130
References
6
Language
en
Licence
Funders
  • National Institute on Aging
  • Alzheimer's Disease Research Foundation
  • U.S. Department of Health and Human Services (ZIA AG000932-03)
  • National Institutes of Health (P50 AG16574, R01 AG18023, R01 NS065782, U01 AG06576)

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