Nghiên cứu kết hợp toàn bộ gen về bệnh Alzheimer khởi phát muộn bằng phương pháp tập hợp DNA
Tóm tắt
Bệnh Alzheimer khởi phát muộn (LOAD) là một bệnh thần kinh thoái hóa liên quan đến tuổi tác với tỷ lệ mắc cao, tạo ra áp lực lớn đối với nguồn lực chăm sóc sức khỏe trong các xã hội có dân số già đi. Yếu tố di truyền có nguy cơ xác định duy nhất cho LOAD là gen apolipoprotein E. Để xác định các locus di truyền nguy cơ bổ sung, chúng tôi đã thực hiện một nghiên cứu liên kết toàn bộ gen (GWA) trên một mẫu case – control lớn của LOAD, giảm chi phí thông qua việc sử dụng phương pháp hòa trộn DNA.
Mẫu DNA được thu thập từ 1.082 cá nhân mắc LOAD và 1.239 chủ thể đối chứng. Độ tuổi khởi phát dao động từ 60 đến 95 và các đối chứng được ghép đôi theo tuổi tác (trung bình = 76,53 năm, SD = 33), giới tính và chủng tộc. Số lượng DNA bằng nhau từ mỗi mẫu được thêm vào hoặc một nhóm trường hợp hoặc nhóm đối chứng. Các nhóm này được genotyped bằng cách sử dụng các mảng Illumina HumanHap300 và Illumina Sentrix HumanHap240S nhằm kiểm tra 561.494 SNP. 114 SNP tốt nhất từ dữ liệu hòa trộn của chúng tôi đã được xác định và sau đó được genotyped riêng lẻ trong mẫu case – control được sử dụng để cấu trúc các nhóm.
Từ khóa
#Bệnh Alzheimer khởi phát muộn #gien apolipoprotein E #nghiên cứu liên kết toàn bộ gen #phương pháp hòa trộn DNA #SNP #LRATTài liệu tham khảo
Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, et al: Global prevalence of dementia: a Delphi consensus study. Lancet. 2005, 366 (9503): 2112-2117. 10.1016/S0140-6736(05)67889-0.
Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A, Pedersen NL: Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006, 63 (2): 168-174. 10.1001/archpsyc.63.2.168.
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.
Wang WY, Barratt BJ, Clayton DG, Todd JA: Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet. 2005, 6 (2): 109-118. 10.1038/nrg1522.
Eberle MA, Ng PC, Kuhn K, Zhou L, Peiffer DA, Galver L, Viaud-Martinez KA, Lawley CT, Gunderson KL, Shen R, et al: Power to detect risk alleles using genome-wide tag SNP panels. PLoS Genet. 2007, 3 (10): 1827-1837. 10.1371/journal.pgen.0030170.
Risch NJ: Searching for genetic determinants in the new millennium. Nature. 2000, 405 (6788): 847-856. 10.1038/35015718.
Cardon LR, Bell JI: Association study designs for complex diseases. Nat Rev Genet. 2001, 2 (2): 91-99. 10.1038/35052543.
MacGregor S, Zhao ZZ, Henders A, Nicholas MG, Montgomery GW, Visscher PM: Highly cost-efficient genome-wide association studies using DNA pools and dense SNP arrays. Nucleic Acids Res. 2008, 36 (6): e35-10.1093/nar/gkm1060.
Kirov G, Nikolov I, Georgieva L, Moskvina V, Owen MJ, O'Donovan MC: Pooled DNA genotyping on Affymetrix SNP genotyping arrays. BMC Genomics. 2006, 7 (1): 27-10.1186/1471-2164-7-27.
Docherty SJ, Butcher LM, Schalkwyk LC, Plomin R: Applicability of DNA pools on 500 K SNP microarrays for cost-effective initial screens in genomewide association studies. BMC Genomics. 2007, 8: 214-10.1186/1471-2164-8-214.
Sham P, Bader JS, Craig I, O'Donovan M, Owen M: DNA Pooling: a tool for large-scale association studies. Nat Rev Genet. 2002, 3 (11): 862-871. 10.1038/nrg930.
Norton N, Williams NM, Williams HJ, Spurlock G, Kirov G, Morris DW, Hoogendoorn B, Owen MJ, O'Donovan MC: Universal, robust, highly quantitative SNP allele frequency measurement in DNA pools. Hum Genet. 2002, 110 (5): 471-478. 10.1007/s00439-002-0706-6.
Pearson JV, Huentelman MJ, Halperin RF, Tembe WD, Melquist S, Homer N, Brun M, Szelinger S, Coon KD, Zismann VL, et al: Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies. Am J Hum Genet. 2007, 80 (1): 126-139. 10.1086/510686.
Saunders AM, Schmader K, Breitner JC, Benson MD, Brown WT, Goldfarb L, Goldgaber D, Manwaring MG, Szymanski MH, McCown N, et al: Apolipoprotein E epsilon 4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases. Lancet. 1993, 342 (8873): 710-711. 10.1016/0140-6736(93)91709-U.
Farrer LA, Cupples LA, van Duijn CM, Kurz A, Zimmer R, Muller U, Green RC, Clarke V, Shoffner J, Wallace DC, et al: Apolipoprotein E genotype in patients with Alzheimer's disease: implications for the risk of dementia among relatives. Ann Neurol. 1995, 38 (5): 797-808. 10.1002/ana.410380515.
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.
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.
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007, 447 (7145): 661-678. 10.1038/nature05911.
Colhoun HM, McKeigue PM, Davey Smith G: Problems of reporting genetic associations with complex outcomes. Lancet. 2003, 361 (9360): 865-872. 10.1016/S0140-6736(03)12715-8.
Goodman AB, Pardee AB: Evidence for defective retinoid transport and function in late onset Alzheimer's disease. Proc Natl Acad Sci USA. 2003, 100 (5): 2901-2905. 10.1073/pnas.0437937100.
Goodman AB: Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease. J Cell Physiol. 2006, 209 (3): 598-603. 10.1002/jcp.20784.
Corcoran JP, So PL, Maden M: Disruption of the retinoid signalling pathway causes a deposition of amyloid beta in the adult rat brain. Eur J Neurosci. 2004, 20 (4): 896-902. 10.1111/j.1460-9568.2004.03563.x.
Morgan AR, Turic D, Jehu L, Hamilton G, Hollingworth P, Moskvina V, Jones L, Lovestone S, Brayne C, Rubinsztein DC, et al: Association studies of 23 positional/functional candidate genes on chromosome 10 in late-onset Alzheimer's disease. Am J Med Genet B Neuropsychiatr Genet. 2007, 144B (6): 762-770. 10.1002/ajmg.b.30509.
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.
Holmes C, Cairns N, Lantos P, Mann A: Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies. Br J Psychiatry. 1999, 174: 45-50. 10.1192/bjp.174.1.45.
Foy CM, Nicholas H, Hollingworth P, Boothby H, Willams J, Brown RG, Al-Sarraj S, Lovestone S: Diagnosing Alzheimer's disease – non-clinicians and computerised algorithms together are as accurate as the best clinical practice. Int J Geriatr Psychiatry. 2007, 22 (11): 1154-1163. 10.1002/gps.1810.
Folstein MF, Folstein SE, McHugh PR: "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975, 12 (3): 189-198. 10.1016/0022-3956(75)90026-6.
Roth M, Tym E, Mountjoy CQ, Huppert FA, Hendrie H, Verma S, Goddard R: CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry. 1986, 149: 698-709. 10.1192/bjp.149.6.698.
Blessed G, Tomlinson BE, Roth M: The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968, 114 (512): 797-811. 10.1192/bjp.114.512.797.
Bucks RS, Ashworth DL, Wilcock GK, Siegfried K: Assessment of activities of daily living in dementia: development of the Bristol Activities of Daily Living Scale. Age Ageing. 1996, 25 (2): 113-120. 10.1093/ageing/25.2.113.
Webster DD: Critical analysis of the disability in Parkinson's disease. Mod Treat. 1968, 5 (2): 257-282.
Reisberg B, Ferris SH, de Leon MJ, Crook T: Global Deterioration Scale (GDS). Psychopharmacol Bull. 1988, 24 (4): 661-663.
Alexopoulos GS, Abrams RC, Young RC, Shamoian CA: Cornell Scale for Depression in Dementia. Biol Psychiatry. 1988, 23 (3): 271-284. 10.1016/0006-3223(88)90038-8.
Cummings JL: The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997, 48 (5 Suppl 6): S10-16.
Sheikh JI, Yesavage JA: A knowledge assessment test for geriatric psychiatry. Hosp Community Psychiatry. 1985, 36 (11): 1160-1166.
Macgregor S: Most pooling variation in array-based DNA pooling is attributable to array error rather than pool construction error. Eur J Hum Genet. 2007, 15 (4): 501-504. 10.1038/sj.ejhg.5201768.
Hoogendoorn B, Norton N, Kirov G, Williams N, Hamshere ML, Spurlock G, Austin J, Stephens MK, Buckland PR, Owen MJ, et al: Cheap, accurate and rapid allele frequency estimation of single nucleotide polymorphisms by primer extension and DHPLC in DNA pools. Hum Genet. 2000, 107 (5): 488-493. 10.1007/s004390000397.
Kirov G, Zaharieva I, Georgieva L, Moskvina V, Nikolov I, Cichon S, Hillmer A, Toncheva D, Owen MJ, O'Donovan MC: A genome-wide association study in 574 schizophrenia trios using DNA pooling. Mol Psychiatry. 2008
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, et al: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007, 81 (3): 559-575. 10.1086/519795.