Alzgene - Putative AD linkage regions based on joint analyses by Hamshere et al. (2007), and meta-analyses by Butler et al. (2009)
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Location (Mb)
Hamshere et al. (2007)
LOD (Mb)
Butler et al. (2009)
1p31.1-q31.1 83–185   0.004-0.05
3q12.3-q25.31 103-173   0.03
6p21.1-q15 43-91   0.02
7pter-q21.11 0–78   0.008-0.04
8p22-p21.1 13–28   0.001
9p22.3-p13.3 20-35 1.2 (~23 Mb)  
9q21.31-q32 80-100 2.5 (~101 Mb)  
10p14-q24 10-100 3.3 (~61 Mb)  
17q24.3-qter 67-79   0.03
19p13.3-qter 8-54 2.0 (~52 Mb) 0.01-0.05

Linkage regions in this table are based on results of the joint (Hamshere et al. [2007]) and meta-analyses (Butler et al. [2009]) of previously published genome-wide linkage (GWL) data. Hamshere et al. (2007) performed their joint analyses using raw data from non-overlapping Caucasian AD families from the UK and the USA, originally reported in Kehoe (1999), Myers (2002), Blacker (2003), Li (2002), Bassett (2002), and Holmans (2005). The meta-analysis by Butler et al. (2009) is based on the Genome Search Meta-Analysis [GSMA] method, and was applied to data from a total of five published GWL scans on AD families previously reported in Lee (2006), Hamshere (2007), Lee (2008), Liu (2007), and Sillen (2008). Note that while the data reported in Hamshere et al. (2007) is also included in the GSMA meta-analyses, it is worth listing the results from both studies separately owing to the differences in methodology (joint raw data vs. GSMA), ethnic background (Caucasian vs. all ethnic groups), and results. The approximate chromosomal intervals of these loci highlighted below are indicated by a red line on the respective chromosome graphs throughout AlzGene (example).

"Location" refers to either to the approximate boundaries of the linkage regions in Figure 1 of Hamshere et al. (2007; converted into physical distance), or bin locations of Table 3 in Butler et al. (2009). Note that adjacent bins are displayed as one contiguous region; this applies to the linkage regions on chromosomes 1, 3, 7, and 19. "LOD (Mb)" is the value and approximate location of the peak multipoint LOD score in Table 1 of Hamshere et al. (2007); "P-value" is the weighted or unweighted summed rank P-value as given in Table 3 of Butler et al (2009). Bold LOD/P-values indicate regions with either genome-wide significant or suggestive evidence for linkage as specified in the two publications.

Please consult the papers by Hamshere et al. (2007) and Butler et al (2009) for more details. Updated GSMA linkage results can also be found at the "alzRES" website maintained by members of the Institute of Psychiatry, King's College London.


Blacker, D., L. Bertram, et al. (2003). "Results of a high-resolution genome screen of 437 Alzheimer's disease families." Hum Mol Genet 12(1): 23-32. Abstract

Butler, A. W., M. Y. Ng, et al. (2009). "Meta-analysis of linkage studies for Alzheimer's disease--a web resource." Neurobiol Aging 30(7): 1037-47. Abstract

Hamshere, M. L., P. A. Holmans, et al. (2007). "Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's disease." Hum Mol Genet 16(22): 2703-12. Abstract

Kehoe, P., F. Wavrant-De Vrieze, et al. (1999). "A full genome scan for late onset Alzheimer's disease." Hum Mol Genet 8(2): 237-45. Abstract

Lee, J. H., R. Cheng, et al. (2008). "Analyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci." Arch Neurol 65(11): 1518-26. Abstract

Lee, J. H., R. Cheng, et al. (2006). "Expanded genomewide scan implicates a novel locus at 3q28 among Caribbean hispanics with familial Alzheimer disease." Arch Neurol 63(11): 1591-8. Abstract

Li, Y. J., W. K. Scott, et al. (2002). "Age at onset in two common neurodegenerative diseases is genetically controlled." Am J Hum Genet 70(4): 985-93. Abstract

Liu, F., A. Arias-Vasquez, et al. (2007). "A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population." Am J Hum Genet 81(1): 17-31. Abstract

Myers, A., F. Wavrant De-Vrieze, et al. (2002). "Full genome screen for Alzheimer disease: stage II analysis." Am J Med Genet 114(2): 235-44. Abstract

Sillen, A., J. Andrade, et al. (2008). "Expanded high-resolution genetic study of 109 Swedish families with Alzheimer's disease." Eur J Hum Genet 16(2): 202-8. Abstract

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