Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease

John S.K. Kauwe; Carlos Cruchaga; Celeste M. Karch; Brooke Sadler; Mo Lee; Kevin Mayo; Wayne Latu; Manti Su'a; Anne M. Fagan; David M. Holtzman; John C. Morris; Alison M. Goate

doi:10.1371/journal.pone.0015918

Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease

John S.K. Kauwe, Carlos Cruchaga, Celeste M. Karch, Brooke Sadler, Mo Lee, Kevin Mayo, Wayne Latu, Manti Su'a, Anne M. Fagan, David M. Holtzman, John C. Morris, Alison M. Goate

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Abstract

Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments (Aβ₄₂) and tau phosphorylated at threonine 181 (ptau₁₈₁), have been obtained. Association analyses were performed to determine whether variants in BIN1, CLU, CR1 or PICALM are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ₄₂ or ptau₁₈₁ levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ₄₂ or ptau₁₈₁.

Original language	English
Article number	e15918
Journal	PLoS ONE
Volume	6
Issue number	2
DOIs	https://doi.org/10.1371/journal.pone.0015918
State	Published - 2011
Externally published	Yes

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Kauwe, J. S. K., Cruchaga, C., Karch, C. M., Sadler, B., Lee, M., Mayo, K., Latu, W., Su'a, M., Fagan, A. M., Holtzman, D. M., Morris, J. C., & Goate, A. M. (2011). Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease. PLoS ONE, 6(2), Article e15918. https://doi.org/10.1371/journal.pone.0015918

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title = "Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease",

abstract = "Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments (Aβ42) and tau phosphorylated at threonine 181 (ptau181), have been obtained. Association analyses were performed to determine whether variants in BIN1, CLU, CR1 or PICALM are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ42 or ptau181 levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ42 or ptau181.",

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AU - Sadler, Brooke

AU - Lee, Mo

AU - Mayo, Kevin

AU - Latu, Wayne

AU - Su'a, Manti

AU - Fagan, Anne M.

AU - Holtzman, David M.

AU - Morris, John C.

AU - Goate, Alison M.

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AB - Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments (Aβ42) and tau phosphorylated at threonine 181 (ptau181), have been obtained. Association analyses were performed to determine whether variants in BIN1, CLU, CR1 or PICALM are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ42 or ptau181 levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ42 or ptau181.

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Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease

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