Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Medical Genetics
Published in: BMC Medical Genetics 1/2009

Open Access 01-12-2009 | Research article

Further analysis of previously implicated linkage regions for Alzheimer's disease in affected relative pairs

Authors: Elin S Blom, Vilmantas Giedraitis, Sampath Arepalli, Marian L Hamshere, Omanma Adighibe, Alison Goate, Julie Williams, Lars Lannfelt, John Hardy, Fabienne Wavrant-De Vrièze, Anna Glaser

Published in: BMC Medical Genetics | Issue 1/2009

Login to get access

Abstract

Background

Genome-wide linkage studies for Alzheimer's disease have implicated several chromosomal regions as potential loci for susceptibility genes.

Methods

In the present study, we have combined a selection of affected relative pairs (ARPs) from the UK and the USA included in a previous linkage study by Myers et al. (Am J Med Genet, 2002), with ARPs from Sweden and Washington University. In this total sample collection of 397 ARPs, we have analyzed linkage to chromosomes 1, 9, 10, 12, 19 and 21, implicated in the previous scan.

Results

The analysis revealed that linkage to chromosome 19q13 close to the APOE locus increased considerably as compared to the earlier scan. However, linkage to chromosome 10q21, which provided the strongest linkage in the previous scan could not be detected.

Conclusion

The present investigation provides yet further evidence that 19q13 is the only chromosomal region consistently linked to Alzheimer's disease.
Appendix
Available only for authorised users
Literature
1.
Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, et al: Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991, 349 (6311): 704-706. 10.1038/349704a0.CrossRefPubMed
2.
Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K: Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature. 1995, 375 (6534): 754-760. 10.1038/375754a0.CrossRefPubMed
3.
Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K, et al: Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science. 1995, 269 (5226): 973-977. 10.1126/science.7638622.CrossRefPubMed
4.
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993, 261 (5123): 921-923. 10.1126/science.8346443.CrossRefPubMed
5.
Seshadri S, Drachman DA, Lippa CF: Apolipoprotein E epsilon 4 allele and the lifetime risk of Alzheimer's disease. What physicians know, and what they should know. Arch Neurol. 1995, 52 (11): 1074-1079.CrossRefPubMed
6.
Slooter AJ, Cruts M, Kalmijn S, Hofman A, Breteler MM, Van Broeckhoven C, van Duijn CM: Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study. Arch Neurol. 1998, 55 (7): 964-968. 10.1001/archneur.55.7.964.CrossRefPubMed
7.
Daw EW, Payami H, Nemens EJ, Nochlin D, Bird TD, Schellenberg GD, Wijsman EM: The number of trait loci in late-onset Alzheimer disease. Am J Hum Genet. 2000, 66 (1): 196-204. 10.1086/302710.CrossRefPubMed
8.
Blacker D, Bertram L, Saunders AJ, Moscarillo TJ, Albert MS, Wiener H, Perry RT, Collins JS, Harrell LE, Go RC, et al: Results of a high-resolution genome screen of 437 Alzheimer's disease families. Hum Mol Genet. 2003, 12 (1): 23-32. 10.1093/hmg/ddg007.CrossRefPubMed
9.
Kehoe P, Wavrant-De Vrieze F, Crook R, Wu WS, Holmans P, Fenton I, Spurlock G, Norton N, Williams H, Williams N, et al: A full genome scan for late onset Alzheimer's disease. Hum Mol Genet. 1999, 8 (2): 237-245. 10.1093/hmg/8.2.237.CrossRefPubMed
10.
Myers A, Wavrant De-Vrieze F, Holmans P, Hamshere M, Crook R, Compton D, Marshall H, Meyer D, Shears S, Booth J, et al: Full genome screen for Alzheimer disease: stage II analysis. Am J Med Genet. 2002, 114 (2): 235-244. 10.1002/ajmg.10183.CrossRefPubMed
11.
Pericak-Vance MA, Bass ML, Yamaoka LH, Gaskell PC, Scott WK, Terwedow HA, Menold MM, Conneally PM, Small GW, Saunders AM, et al: Complete genomic screen in late-onset familial Alzheimer's disease. Neurobiol Aging. 1998, 19 (1 Suppl): S39-42. 10.1016/S0197-4580(98)00037-2.CrossRefPubMed
12.
Pericak-Vance MA, Grubber J, Bailey LR, Hedges D, West S, Santoro L, Kemmerer B, Hall JL, Saunders AM, Roses AD, et al: Identification of novel genes in late-onset Alzheimer's disease. Exp Gerontol. 2000, 35 (9-10): 1343-1352. 10.1016/S0531-5565(00)00196-0.CrossRefPubMed
13.
Sillén A, Andrade J, Lilius L, Forsell C, Axelman K, Odeberg J, Winblad B, Graff C: Expanded high-resolution genetic study of 109 Swedish families with Alzheimer's disease. Eur J Hum Genet. 2008, 16 (2): 202-208. 10.1038/sj.ejhg.5201946.CrossRefPubMed
14.
Sillén A, Forsell C, Lilius L, Axelman K, Bjork BF, Onkamo P, Kere J, Winblad B, Graff C: Genome scan on Swedish Alzheimer's disease families. Mol Psychiatry. 2006, 11 (2): 182-186. 10.1038/sj.mp.4001772.CrossRefPubMed
15.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984, 34 (7): 939-944.CrossRefPubMed
16.
Giedraitis V, Hedlund M, Skoglund L, Blom E, Ingvast S, Brundin R, Lannfelt L, Glaser A: New Alzheimer's disease locus on chromosome 8. J Med Genet. 2006
17.
Dausset J, Cann H, Cohen D, Lathrop M, Lalouel JM, White R: Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. Genomics. 1990, 6 (3): 575-577. 10.1016/0888-7543(90)90491-C.CrossRefPubMed
18.
Broman KW, Murray JC, Sheffield VC, White RL, Weber JL: Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet. 1998, 63 (3): 861-869. 10.1086/302011.CrossRefPubMedPubMedCentral
19.
Abecasis GR, Cherny SS, Cookson WO, Cardon LR: GRR: graphical representation of relationship errors. Bioinformatics. 2001, 17 (8): 742-743. 10.1093/bioinformatics/17.8.742.CrossRefPubMed
20.
Lange K, Cantor R, Horvath S, Perola M, Sabatti C, Sinsheimer J, Sobel E: Mendel version 4.0: A complete package for the exact genetic analysis of discrete traits in pedigree and population data sets. Amer J Hum Genetics. 2001, 69 (supplement): A1886-
21.
Mukhopadhyay N, Almasy L, Schroeder M, Mulvihill WP, Weeks DE: Mega2: data-handling for facilitating genetic linkage and association analyses. Bioinformatics. 2005, 21 (10): 2556-2557. 10.1093/bioinformatics/bti364.CrossRefPubMed
22.
Gudbjartsson DF, Thorvaldsson T, Kong A, Gunnarsson G, Ingolfsdottir A: Allegro version 2. Nat Genet. 2005, 37 (10): 1015-1016. 10.1038/ng1005-1015.CrossRefPubMed
23.
Lander E, Kruglyak L: Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995, 11 (3): 241-247. 10.1038/ng1195-241.CrossRefPubMed
24.
Meyer MR, Tschanz JT, Norton MC, Welsh-Bohmer KA, Steffens DC, Wyse BW, Breitner JC: APOE genotype predicts when - not whether - one is predisposed to develop Alzheimer disease. Nat Genet. 1998, 19 (4): 321-322. 10.1038/1206.CrossRefPubMed
25.
Blom ES, Holmans P, Arepalli S, Adighibe O, Hamshere ML, Gatz M, Pedersen NL, Bergem AL, Owen MJ, Hollingworth P, et al: Does APOE explain the linkage of Alzheimer's disease to chromosome 19q13?. Am J Med Genet B Neuropsychiatr Genet. 2008, 147B (6): 778-783. 10.1002/ajmg.b.30681.CrossRefPubMedPubMedCentral
26.
Coon KD, Myers AJ, Craig DW, Webster JA, Pearson JV, Lince DH, Zismann VL, Beach TG, Leung D, Bryden L, et al: A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease. J Clin Psychiatry. 2007, 68 (4): 613-618. 10.4088/JCP.v68n0419.CrossRefPubMed
27.
Grupe A, Abraham R, Li Y, Rowland C, Hollingworth P, Morgan A, Jehu L, Segurado R, Stone D, Schadt E, et al: Evidence for novel susceptibility genes for late-onset Alzheimer's disease from a genome-wide association study of putative functional variants. Hum Mol Genet. 2007, 16 (8): 865-873. 10.1093/hmg/ddm031.CrossRefPubMed
28.
Li H, Wetten S, Li L, St Jean PL, Upmanyu R, Surh L, Hosford D, Barnes MR, Briley JD, Borrie M, et al: Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Arch Neurol. 2008, 65 (1): 45-53. 10.1001/archneurol.2007.3.CrossRefPubMed
29.
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Wellcome Trust Case Control Consortium. Nature. 2007, 447 (7145): 661-678. 10.1038/nature05911.
30.
Hardy J, Myers A, Wavrant-De Vrieze F: Problems and solutions in the genetic analysis of late-onset Alzheimer's disease. Neurodegener Dis. 2004, 1 (4-5): 213-217. 10.1159/000080988.CrossRefPubMed
Metadata
Title
Further analysis of previously implicated linkage regions for Alzheimer's disease in affected relative pairs
Authors
Elin S Blom
Vilmantas Giedraitis
Sampath Arepalli
Marian L Hamshere
Omanma Adighibe
Alison Goate
Julie Williams
Lars Lannfelt
John Hardy
Fabienne Wavrant-De Vrièze
Anna Glaser
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2009
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-10-122

Other articles of this Issue 1/2009

BMC Medical Genetics 1/2009 Go to the issue

Research article

The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

Research article

Multiple splice defects in ABCA1cause low HDL-C in a family with Hypoalphalipoproteinemia and premature coronary disease

Research article

PRNP variation in UK sporadic and variant Creutzfeldt Jakob disease highlights genetic risk factors and a novel non-synonymous polymorphism

Research article

PPARγ Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

Research article

Association of vitamin D receptor polymorphisms with the risk of prostate cancer in the Han population of Southern China

Research article

Prevalence of pathogenetic MC4R mutations in Italian children with early Onset obesity, tall stature and familial history of obesity