Identification of rare variants in Alzheimer's disease

Frontiers in Genetics

Volumn 5, Issue OCT, 2014, Pages

  Lord, Jenny ^a   Lu, Alexander J ^a   Cruchaga, Carlos ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Alzheimer's disease; Exome sequencing; Genome sequencing; Population differences; Rare variants; Replication

Indexed keywords

ADAM10 GENE; AKAP9 GENE; ALZHEIMER DISEASE; APOE GENE; EXOME; GENE; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; HERITABILITY; HUMAN; META ANALYSIS (TOPIC); MISSENSE MUTATION; NONHUMAN; PLD3 GENE; REVIEW; SORL1 GENE; TREM2 GENE; UNC5C GENE;

ANIMALIA;

EID: 84917694860     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2014.00369     Document Type: Review

References (67)

1. Abecasis, G. R., Altshuler, D., Auton, A., Brooks, L. D., Durbin, R. M., Gibbs, R. A.,et al. (2010). A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073. doi: 10.1038/nature09534
2. Alzheimer's Association Statistics. (2014). 2014 Alzheime's Disease Facts and Figures. Available at: www.alz.org/downloads/facts_figures_2014.pdf
3. Bamne, M. N., Demirci, F. Y., Berman, S., Snitz, B. E., Rosenthal, S. L., Wang, X.,et al. (2014). Investigation of an amyloid precursor protein protective mutation (A673T) in a North American case-control sample of late-onset Alzheimer's disease. Neurobiol. Aging 35, 1779.e1715-1779.e1776. doi: 10.1016/j.neurobiolaging.2014.01.020
4. Benitez, B. A., Cooper, B., Pastor, P., Jin, S. C., Lorenzo, E., Cervantes, S.,et al. (2013a). TREM2 is associated with the risk of Alzheimer's disease in Spanish population. Neurobiol. Aging 34, 1711.e1715-1711.e1717. doi: 10.1016/j.neurobiolaging.2012.12.018
5. Benitez, B. A., Karch, C. M., Cai, Y., Jin, S. C., Cooper, B., Carrell, D.,et al. (2013b). The PSEN1, p.E318G variant increases the risk of Alzheimer's disease in APOE-e4 carriers. PLoS Genet. 9:e1003685. doi: 10.1371/journal.pgen.1003685
6. Bettens, K., Brouwers, N., Engelborghs, S., Lambert, J. C., Rogaeva, E., Vandenberghe, R.,et al. (2012). Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk. Mol. Neurodegener. 7, 3. doi: 10.1186/1750-1326-7-3
7. Brookmeyer, R., Johnson, E., Ziegler-Graham, K., and Arrighi, H. M. (2007). Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 3, 186-191. doi: 10.1016/j.jalz.2007.04.381
8. Cai, G., Atzmon, G., Naj, A. C., Beecham, G. W., Barzilai, N., Haines, J. L.,et al. (2012). Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer disease. Neurobiol. Aging 33, 416-417. doi: 10.1016/j.neurobiolaging.2010.03.003
9. Carrasquillo, M. M., Belbin, O., Hunter, T. A., Ma, L., Bisceglio, G. D., Zou, F.,et al. (2010). Replication of CLU, CR1, and PICALM associations with alzheimer disease. Arch. Neurol. 67, 961-964. doi: 10.1001/archneurol.2010.147
10. Chung, S. J., Kim, M. J., Kim, J., Kim, Y. J., You, S., Koh, J.,et al. (2014). Exome array study did not identify novel variants in Alzheimer's disease. Neurobiol. Aging 35, 1958.e1913-1958.e1914. doi: 10.1016/j.neurobiolaging.2014.03.007
11. Cirulli, E. T., and Goldstein, D. B. (2010). Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat. Rev. Genet. 11, 415-425. doi: 10.1038/nrg2779
12. Cobat, A., Abel, L., Alcais, A., and Schurr, E. (2014). A general efficient and flexible approach for genome-wide association analyses of imputed genotypes in family-based designs. Genet. Epidemiol. 38, 560-571. doi: 10.1002/gepi.21842
13. Corneveaux, J. J., Myers, A. J., Allen, A. N., Pruzin, J. J., Ramirez, M., Engel, A.,et al. (2010). Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals. Hum. Mol. Genet. 19, 3295-3301. doi: 10.1093/hmg/ddq221
14. Cruchaga, C., Karch, C. M., Jin, S. C., Benitez, B. A., Cai, Y., Guerreiro, R.,et al. (2014). Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease. Nature 505, 550-554. doi: 10.1038/nature12825
15. Cuyvers, E., Bettens, K., Philtjens, S., Van Langenhove, T., Gijselinck, I., van der Zee, J.,et al. (2014). Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia. Neurobiol. Aging 35, 726.e711-726.e729. doi: 10.1016/j.neurobiolaging.2013.09.009
16. De Jager, P. L., Srivastava, G., Lunnon, K., Burgess, J., and Schalkwyk, L. C. (2014). Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat. Neurosci. 17, 1156-1163. doi: 10.1038/nn.3786
17. Do, R., Kathiresan, S., and Abecasis, G. R. (2012). Exome sequencing and complex disease: practical aspects of rare variant association studies. Hum. Mol. Genet. 21, R1-R9. doi: 10.1093/hmg/dds387
18. Ertekin-Taner, N. (2010). Genetics of Alzheimer disease in the pre- and post-GWAS era. Alzheimers Res. Ther. 2, 3. doi: 10.1186/alzrt26
19. Farrer, L. A., Cupples, L. A., Haines, J. L., Hyman, B., Kukull, W. A., Mayeux, R.,et al. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer disease meta analysis consortium. JAMA 278, 1349-1356. doi: 10.1001/jama.1997.03550160069041
20. Ferrari, R., Moreno, J. H., Minhajuddin, A. T., O'Bryant, S. E., Reisch, J. S., Barber, R. C.,et al. (2012). Implication of common and disease specific variants in CLU, CR1, and PICALM. Neurobiol. Aging 33, 1846.e7-1846.e18. doi: 10.1016/j.neurobiolaging.2012.01.110
21. Gatz, M., Reynolds, C. A., Fratiglioni, L., Johansson, B., Mortimer, J. A., Berg, S.,et al. (2006). Role of genes and environments for explaining Alzheimer disease. Arch. Gen. Psychiatry 63, 168-174. doi: 10.1001/archpsyc.63.2.168
22. Gibson, G. (2011). Rare and common variants: twenty arguments. Nat. Rev. Genet. 13, 135-145. doi: 10.1038/nrg3118
23. Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E.,et al. (2013). TREM2 variants in Alzheimer's disease. N. Engl. J. Med. 368, 117-127. doi: 10.1056/NEJMoa1211851
24. Guerreiro, R. J., Beck, J., Gibbs, J. R., Santana, I., Rossor, M. N., Schott, J. M.,et al. (2010). Genetic variability in CLU and its association with Alzheimer's disease. PLoS ONE 5:e9510. doi: 10.1371/journal.pone.0009510
25. Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L.,et al. (2009). Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat. Genet. 41, 1088-1093. doi: 10.1038/ng.440
26. Hatzikotoulas, K., Gilly, A., and Zeggini, E. (2014). Using population isolates in genetic association studies. Brief Funct. Genomics 13, 371-377. doi: 10.1093/bfgp/elu022
27. Hollingworth, P., Harold, D., Sims, R., Gerrish, A., Lambert, J. C., Carrasquillo, M. M.,et al. (2011). Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat. Genet. 43, 429-435. doi: 10.1038/ng.803
28. Hunkapiller, J., Wetzel, M., Bhangale, T., Maloney, J., Atwal, J., Ortmann, W.,et al. (2013). A rare coding variant alters UNC5C function and predisposes to Alzheimer's disease. J. Alzheimer's Assoc. 9, 853. doi: 10.1016/j.jalz.2013.08.163
29. Hunt, K. A., Mistry, V., Bockett, N. A., Ahmad, T., Ban, M., Barker, J. N.,et al. (2013). Negligible impact of rare autoimmune-locus coding-region variants on missing heritability. Nature 498, 232-235. doi: 10.1038/nature12170
30. Huyghe, J. R., Jackson, A. U., Fogarty, M. P., Buchkovich, M. L., Stancakova, A., Stringham, H. M.,et al. (2013). Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. Nat. Genet. 45, 197-201. doi: 10.1038/ng.2507
31. Jiao, B., Liu, X., Tang, B., Hou, L., Zhou, L., Zhang, F.,et al. (2014). Investigation of TREM2, PLD3, and UNC5C variants in patients with Alzheimer's disease from mainland China. Neurobiol. Aging 35, 2422.e2429-2422.e2411. doi: 10.1016/j.neurobiolaging.2014.04.025
32. Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D.,et al. (2014). Coding variants in TREM2 increase risk for Alzheimer's disease. Hum. Mol. Genet. doi: 10.1093/hmg/ddu277 [Epub ahead of print].
33. Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S.,et al. (2012). A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488, 96-99. doi: 10.1038/nature11283
34. Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J.,et al. (2013). Variant of TREM2 associated with the risk of Alzheimer's disease. N. Engl. J. Med. 368, 107-116. doi: 10.1056/NEJMoa1211103
35. Jun, G., Naj, A. C., Beecham, G. W., Wang, L. S., Buros, J., Gallins, P. J.,et al. (2010). Meta-analysis confirms CR1, CLU, and PICALM as Alzheimer disease risk loci and reveals interactions with APOE genotypes. Arch. Neurol. 67, 1473-1484. doi: 10.1001/archneurol.2010.201
36. Keen-Kim, D., Mathews, C. A., Reus, V. I., Lowe, T. L., Herrera, L. D., Budman, C. L.,et al. (2006). Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses. Hum. Mol. Genet. 15, 3324-3328. doi: 10.1093/hmg/ddl408
37. Kero, M., Paetau, A., Polvikoski, T., Tanskanen, M., Sulkava, R., Jansson, L.,et al. (2013). Amyloid precursor protein (APP) A673T mutation in the elderly Finnish population. Neurobiol. Aging 34, 1518.e1511-1518.e1513. doi: 10.1016/j.neurobiolaging.2012.09.017
38. Kim, M., Suh, J., Romano, D., Truong, M. H., Mullin, K., Hooli, B.,et al. (2009). Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity. Hum. Mol. Genet. 18, 3987-3996. doi: 10.1093/hmg/ddp323
39. Lambert, J. C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M.,et al. (2009). Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat. Genet. 41, 1094-1099. doi: 10.1038/ng.439
40. Lambert, J. C., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C.,et al. (2013). Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat. Genet. 45, 1452-1458. doi: 10.1038/ng.2802
41. Lee, S., Abecasis, G. R., Boehnke, M., and Lin, X. (2014). Rare-variant association analysis: study designs and statistical tests. Am. J. Hum. Genet. 95, 5-23. doi: 10.1016/j.ajhg.2014.06.009
42. Lee, S., Wu, M. C., and Lin, X. (2012). Optimal tests for rare variant effects in sequencing association studies. Biostatistics 13, 762-775. doi: 10.1093/biostatistics/kxs014
43. Li, D., Lewinger, J. P., Gauderman, W. J., Murcray, C. E., and Conti, D. (2011). Using extreme phenotype sampling to identify the rare causal variants of quantitative traits in association studies. Genet. Epidemiol. 35, 790-799. doi: 10.1002/gepi.20628
44. Liu, Q., Nicolae, D. L., and Chen, L. S. (2013). Marbled inflation from population structure in gene-based association studies with rare variants. Genet. Epidemiol. 37, 286-292. doi: 10.1002/gepi.21714
45. Liu, Y. W., He, Y. H., Zhang, Y. X., Cai, W. W., Yang, L. Q., Xu, L. Y.,et al. (2014). Absence of A673T variant in APP gene indicates an alternative protective mechanism contributing to longevity in Chinese individuals. Neurobiol. Aging 35, 935.e911-935.e932. doi: 10.1016/j.neurobiolaging.2013.09.023
46. Logue, M., Schu, M., Vardarajan, B., Farrell, J., Lunetta, K., Baldwin, C.,et al. (2014). Two rare AKAP9 variants are associated with Alzheimers disease in African Americans. Alzheimer's Dement. doi: 10.1016/j.jalz.2014.06.010 [Epub ahead of print].
47. Lord, J., and Cruchaga, C. (2014). The epigenetic landscape of Alzheimer's disease. Nat. Neurosci. 17, 1138-1140. doi: 10.1038/nn.3792
48. Lunnon, K., Smith, R., Hannon, E., De Jager, P. L., Srivastava, G., Volta, M.,et al. (2014). Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. Nat. Neurosci. 17, 1164-1170. doi: 10.1038/ nn.3782
49. Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J.,et al. (2009). Finding the missing heritability of complex diseases. Nature 461, 747-753. doi: 10.1038/nature08494
50. Medway, C. W., Abdul-Hay, S., Mims, T., Ma, L., Bisceglio, G., Zou, F.,et al. (2014). ApoE variant p.V236E is associated with markedly reduced risk of Alzheimer's disease. Mol. Neurodegener. 9, 11. doi: 10.1186/1750-1326-9-11
51. Miyashita, A., Wen, Y., Kitamura, N., Matsubara, E., Kawarabayashi, T., Shoji, M.,et al. (2014). Lack of genetic association between TREM2 and late-onset Alzheimer's disease in a Japanese population. J. Alzheimers. Dis. 41, 1031-1038. doi: 10.3233/JAD-140225
52. Morris, A. P., and Zeggini, E. (2010). An evaluation of statistical approaches to rare variant analysis in genetic association studies. Genet. Epidemiol. 34, 188-193. doi: 10.1002/gepi.20450
53. Naj, A. C., Jun, G., Beecham, G. W., Wang, L. S., Vardarajan, B. N., Buros, J.,et al. (2011). Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat. Genet. 43, 436-441. doi: 10.1038/ng.801
54. Ng, S. B., Turner, E. H., Robertson, P. D., Flygare, S. D., Bigham, A. W., Lee, C.,et al. (2009). Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461, 272-276. doi: 10.1038/nature08250
55. O'Rawe, J., Jiang, T., Sun, G., Wu, Y., Wang, W., Hu, J.,et al. (2013). Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing. Genome. Med. 5, 28. doi: 10.1186/gm432
56. Pericak-Vance, M. A., Bebout, J. L., Gaskell, P. C. Jr., Yamaoka, L. H., Hung, W. Y., Alberts, M.J.,et al. (1991). Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am. J. Hum. Genet. 48, 1034-1050.
57. Pottier, C., Hannequin, D., Coutant, S., Rovelet-Lecrux, A., Wallon, D., Rousseau, S.,et al. (2012). High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease. Mol. Psychiatry 17, 875-879. doi: 10.1038/mp.2012.15
58. Pottier, C., Wallon, D., Rousseau, S., Rovelet-Lecrux, A., Richard, A. C., Rollin-Sillaire, A.,et al. (2013). TREM2 R47H variant as a risk factor for early-onset Alzheimer's disease. J. Alzheimers. Dis. 35, 45-49. doi: 10.3233/JAD-122311
59. Raska, P., and Zhu, X. (2011). Rare variant density across the genome and across populations. BMC Proc. 5(Suppl. 9):S39. doi: 10.1186/1753-6561-5-S9-S39
60. Rivas, M. A., Beaudoin, M., Gardet, A., Stevens, C., Sharma, Y., Zhang, C. K.,et al. (2011). Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat. Genet. 43, 1066-1073. doi: 10.1038/ng.952
61. Saad, M., and Wijsman, E. M. (2014). Combining family- and population-based imputation data for association analysis of rare and common variants in large pedigrees. Genet. Epidemiol. 38, 579-590. doi: 10.1002/gepi.21844
62. Santorico, S. A., and Edwards, K. L. (2014). Challenges of linkage analysis in the era of whole-genome sequencing. Genet. Epidemiol. 38(Suppl. 1), S92-S96. doi: 10.1002/gepi.21832
63. Scherzer, C. R., Offe, K., Gearing, M., Rees, H. D., Fang, G., Heilman, C. J.,et al. (2004). Loss of apolipoprotein E receptor LR11 in Alzheimer disease. Arch. Neurol. 61, 1200-1205. doi: 10.1001/archneur.61.8.1200
64. Seshadri, S., Fitzpatrick, A. L., Ikram, M. A., DeStefano, A. L., Gudnason, V., Boada, M.,et al. (2010). Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303, 1832-1840. doi: 10.1001/jama.2010.574
65. Ting, S. K., Chong, M. S., Kandiah, N., Hameed, S., Tan, L., Au, W. L.,et al. (2013). Absence of A673T amyloid-beta precursor protein variant in Alzheimer's disease and other neurological diseases. Neurobiol. Aging 34, 2441.e2447-2441.e2448. doi: 10.1016/j.neurobiolaging.2013.04.012
66. Wang, Z., Liu, X., Yang, B. Z., and Gelernter, J. (2013). The role and challenges of exome sequencing in studies of human diseases. Front. Genet. 4:160. doi: 10.3389/fgene.2013.00160
67. Yu, J. T., Jiang, T., Wang, Y. L., Wang, H. F., Zhang, W., Hu, N.,et al. (2014). Triggering receptor expressed on myeloid cells 2 variant is rare in late-onset Alzheimer's disease in Han Chinese individuals. Neurobiol. Aging 35, 937.e931-937.e933. doi: 10.1016/j.neurobiolaging.2013.10.075