Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease

Minerva M. Carrasquillo; Fanggeng Zou; V. Shane Pankratz; Samantha L. Wilcox; Li Ma; Louise P. Walker; Samuel G. Younkin; Curtis S. Younkin; Linda H. Younkin; Gina D. Bisceglio; Nilufer Ertekin-Taner; Julia E. Crook; Dennis W. Dickson; Ronald C. Petersen; Neill R. Graff-Radford; Steven G. Younkin

doi:10.1038/ng.305

Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease

Minerva M. Carrasquillo, Fanggeng Zou, V. Shane Pankratz, Samantha L. Wilcox, Li Ma, Louise P. Walker, Samuel G. Younkin, Curtis S. Younkin, Linda H. Younkin, Gina D. Bisceglio, Nilufer Ertekin-Taner, Julia E. Crook, Dennis W. Dickson, Ronald C. Petersen, Neill R. Graff-Radford, Steven G. Younkin

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Abstract

By analyzing late-onset Alzheimer's disease (LOAD) in a genome-wide association study (313,504 SNPs, three series, 844 cases and 1,255 controls) and evaluating the 25 SNPs with the most significant allelic association in four additional series (1,547 cases and 1,209 controls), we identified a SNP (rs5984894) on Xq21.3 in PCDH11X that is strongly associated with LOAD in individuals of European descent from the United States. Analysis of rs5984894 by multivariable logistic regression adjusted for sex gave global P values of 5.7 × 10^-5 in stage 1, 4.8 × 10^-6 in stage 2 and 3.9 × 10^-12 in the combined data. Odds ratios were 1.75 (95% CI = 1.42-2.16) for female homozygotes (P = 2.0 × 10^-7) and 1.26 (95% CI = 1.05-1.51) for female heterozygotes (P = 0.01) compared to female noncarriers. For male hemizygotes (P = 0.07) compared to male noncarriers, the odds ratio was 1.18 (95% CI = 0.99-1.41).

Original language	English (US)
Pages (from-to)	192-198
Number of pages	7
Journal	Nature Genetics
Volume	41
Issue number	2
DOIs	https://doi.org/10.1038/ng.305
State	Published - Feb 2009

ASJC Scopus subject areas

Genetics

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Carrasquillo, M. M., Zou, F., Pankratz, V. S., Wilcox, S. L., Ma, L., Walker, L. P., Younkin, S. G., Younkin, C. S., Younkin, L. H., Bisceglio, G. D., Ertekin-Taner, N., Crook, J. E., Dickson, D. W., Petersen, R. C., Graff-Radford, N. R., & Younkin, S. G. (2009). Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease. Nature Genetics, 41(2), 192-198. https://doi.org/10.1038/ng.305

Carrasquillo, MM, Zou, F, Pankratz, VS, Wilcox, SL, Ma, L, Walker, LP, Younkin, SG, Younkin, CS, Younkin, LH, Bisceglio, GD, Ertekin-Taner, N, Crook, JE, Dickson, DW , Petersen, RC , Graff-Radford, NR & Younkin, SG 2009, 'Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease', Nature Genetics, vol. 41, no. 2, pp. 192-198. https://doi.org/10.1038/ng.305

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title = "Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease",

abstract = "By analyzing late-onset Alzheimer's disease (LOAD) in a genome-wide association study (313,504 SNPs, three series, 844 cases and 1,255 controls) and evaluating the 25 SNPs with the most significant allelic association in four additional series (1,547 cases and 1,209 controls), we identified a SNP (rs5984894) on Xq21.3 in PCDH11X that is strongly associated with LOAD in individuals of European descent from the United States. Analysis of rs5984894 by multivariable logistic regression adjusted for sex gave global P values of 5.7 × 10-5 in stage 1, 4.8 × 10-6 in stage 2 and 3.9 × 10-12 in the combined data. Odds ratios were 1.75 (95% CI = 1.42-2.16) for female homozygotes (P = 2.0 × 10-7) and 1.26 (95% CI = 1.05-1.51) for female heterozygotes (P = 0.01) compared to female noncarriers. For male hemizygotes (P = 0.07) compared to male noncarriers, the odds ratio was 1.18 (95% CI = 0.99-1.41).",

author = "Carrasquillo, {Minerva M.} and Fanggeng Zou and Pankratz, {V. Shane} and Wilcox, {Samantha L.} and Li Ma and Walker, {Louise P.} and Younkin, {Samuel G.} and Younkin, {Curtis S.} and Younkin, {Linda H.} and Bisceglio, {Gina D.} and Nilufer Ertekin-Taner and Crook, {Julia E.} and Dickson, {Dennis W.} and Petersen, {Ronald C.} and Graff-Radford, {Neill R.} and Younkin, {Steven G.}",

note = "Funding Information: Support for this research was provided by grants from the US National Institutes of Health, NIA R01 AG18023 (N.R.G.-R., Steven G. Younkin); Mayo Alzheimer{\textquoteright}s Disease Research Center, P50 AG16574 (R.C.P., D.W.D., N.R.G.-R., Steven G. Younkin); Mayo Alzheimer{\textquoteright}s Disease Patient Registry, U01 AG06576 (R.C.P.); and US National Institute on Aging, AG25711, AG17216, AG03949 (D.W.D.). Samples from the National Cell Repository for Alzheimer{\textquoteright}s Disease (NCRAD), which",

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doi = "10.1038/ng.305",

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AU - Carrasquillo, Minerva M.

AU - Zou, Fanggeng

AU - Pankratz, V. Shane

AU - Wilcox, Samantha L.

AU - Ma, Li

AU - Walker, Louise P.

AU - Younkin, Samuel G.

AU - Younkin, Curtis S.

AU - Younkin, Linda H.

AU - Bisceglio, Gina D.

AU - Ertekin-Taner, Nilufer

AU - Crook, Julia E.

AU - Dickson, Dennis W.

AU - Petersen, Ronald C.

AU - Graff-Radford, Neill R.

AU - Younkin, Steven G.

N1 - Funding Information: Support for this research was provided by grants from the US National Institutes of Health, NIA R01 AG18023 (N.R.G.-R., Steven G. Younkin); Mayo Alzheimer’s Disease Research Center, P50 AG16574 (R.C.P., D.W.D., N.R.G.-R., Steven G. Younkin); Mayo Alzheimer’s Disease Patient Registry, U01 AG06576 (R.C.P.); and US National Institute on Aging, AG25711, AG17216, AG03949 (D.W.D.). Samples from the National Cell Repository for Alzheimer’s Disease (NCRAD), which

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Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease

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