Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk

Karolien Bettens; Nathalie Brouwers; Sebastiaan Engelborghs; Jean-Charles Lambert; Ekaterina Rogaeva; Rik Vandenberghe; Nathalie Le Bastard; Florence Pasquier; Steven Vermeulen; Jasper Van Dongen; Maria Mattheijssens; Karin Peeters; Richard Mayeux; Peter St George-Hyslop; Philippe Amouyel; Peter P De Deyn; Kristel Sleegers; Christine Van Broeckhoven

doi:10.1186/1750-1326-7-3

Table 6 Common CLU associations with AD.

From: Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk

(A) Allelic associations in stage I and II AD cohorts
		Belgian-Flanders				Lille				Toronto
	Allele	AD (total)	C (total)	OR [95% CI]	p	AD (total)	C (total)	OR [95% CI]	p	AD (total)	C (total)	OR [95% CI]	p
rs867230	T	0.63 (1259)	0.59 (952)		0.074 ⁽¹⁾	0.66 (1736)	0.62 (742)		0.022 ⁽¹⁾	0.60 (367)	0.63 (307)		0.288 ⁽¹⁾
Intron 1	G	0.37 (752)	0.41 (670)	0.82 [0.70-0.96]	0.012 ⁽²⁾	0.34 (904)	0.38 (456)	0.89 [0.76-1.04]	0.144 ⁽²⁾	0.40 (247)	0.37 (181)	1.04 [0.80-1.36]	0.771 ⁽²⁾
rs1532278	G	0.63 (1308)	0.61 (1006)		< 0.01 ⁽¹⁾	0.675 (1789)	0.628 (764)		0.004 ⁽¹⁾	0.62 (383)	0.62 (301)		0.996 ⁽¹⁾
Intron 3	A	0.37 (770)	0.40 (656)	0.83 [0.71-0.97]	0.019 ⁽²⁾	0.325 (861)	0.372 (452)	0.83 [0.71-0.97]	0.02 ⁽²⁾	0.38 (233)	0.38 (183)	1.27 [0.97-1.64]	0.078 ⁽²⁾
rs11136000	G	0.65 (1232)	0.61 (990)		0.034 ⁽¹⁾	0.66 (1707)	0.628 (764)		0.195 ⁽¹⁾	0.61 (372)	0.63 (299)		0.645 ⁽¹⁾
Intron 3	A	0.35 (676)	0.39 (630)	0.79 [0.68-0.93]	0.004 ⁽²⁾	0.34 (875)	0.372 (452)	0.93 [0.79-1.10]	0.400 ⁽²⁾	0.39 (236)	0.37 (179)	1.00 [0.77-1.31]	0.986 ⁽²⁾
rs9331908	G	0.66 (1389)	0.69 (1161)		0.055 ⁽¹⁾	0.62 (1712)	0.66 (841)		0.036 ⁽¹⁾	0.66 (416)	0.69 (338)		0.297 ⁽¹⁾
Intron 4	A	0.34 (713)	0.31 (521)	1.18 [1.01-1.39]	0.035 ⁽²⁾	0.38 (1046)	0.35 (443)	1.12 [0.96-1.30]	0.156 ⁽²⁾	0.34 (214)	0.31 (152)	1.20 [0.91-1.56]	0.198 ⁽²⁾
rs7982	C	0.63 (1228)	0.61 (1005)		0.191 ⁽¹⁾	0.67 (1780)	0.63 (804)		0.022 ⁽¹⁾	0.62 (374)	0.60 (295)		0.434 ⁽¹⁾
Exon 5	T	0.37 (734)	0.40 (657)	0.85 [0.73-0.99]	0.037 ⁽²⁾	0.33 (884)	0.37 (470)	0.89 [0.76-1.03]	0.124 ⁽²⁾	0.38 (234)	0.36 (167)	1.16 [0.89-1.52]	0.273 ⁽²⁾
*(B) Meta-analysis of stage I and II AD cohorts*
	Allele	Summary OR	p _MH	p _Bonf	p _woolf'
rs867230	T
Intron 1	G	0.88 [0.79-0.97]	0.013	0.065	0.311
rs1532278	G
Intron 3	A	0.85 [0.77-0.94]	0.001	0.005	0.648
rs11136000	G
Intron 3	A	0.88 [0.79-0.97]	0.013	0.065	0.206
rs9331908	G
Intron 4	A	1.16 [1.04-1.28]	0.006	0.030	0.824
rs7982	C
Exon 5	T	0.89 [0.80-0.98]	0.023	0.115	0.448

(A) Allele frequencies are shown with absolute numbers in brackets. ⁽¹⁾ The first p-value is the 2-sided p-value of the unadjusted χ² statistics, ⁽²⁾ The second p-value is adjusted for age, APOE status and gender. Calculations of odds ratios (OR), presented with 95% confidence intervals (CI), were performed using the common allele as reference allele. (B) For meta-analysis, Mantel-Haenszel summary OR ratios are given with 95% CI and corresponding p-values (p_MH) based on fixed-effects meta-analysis of age, gender and APOE- adjusted effect estimates of the minor allele. Nominal p-values (p_mh, adjusted for age, gender and APOE effects) and Bonferroni corrected p-values (p _Bonf) for the number of SNPs (N = 5) in the meta-analysis are given. P-values of Woolf's test for heterogeneity (p-_woolf) are given.

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