Manuel Mattheisen

Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3

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Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3. / Herold, C; Hooli, B V; Mullin, K; Liu, T; Roehr, J T; Mattheisen, M; Parrado, A R; Bertram, L; Lange, C; Tanzi, R E.

In: Molecular Psychiatry, 02.02.2016.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Herold, C., Hooli, B. V., Mullin, K., Liu, T., Roehr, J. T., Mattheisen, M., Parrado, A. R., Bertram, L., Lange, C., & Tanzi, R. E. (2016). Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3. Molecular Psychiatry. https://doi.org/10.1038/mp.2015.218

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Herold, C ; Hooli, B V ; Mullin, K ; Liu, T ; Roehr, J T ; Mattheisen, M ; Parrado, A R ; Bertram, L ; Lange, C ; Tanzi, R E. / Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3. In: Molecular Psychiatry. 2016.

Bibtex

@article{67e769ff1c2f4523a236bbcba0f7eba0,
title = "Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3",
abstract = "The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1, and PSEN2 cause a subset of early-onset familial AD. On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ɛ4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study, we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3500 subjects from 1070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value=3.98 × 10(-8)), rs1347297 in the gene OSBPL6 (P-value=4.53 × 10(-8)), and rs1513625 near PDCL3 (P-value=4.28 × 10(-8)). In addition, rs72953347 in OSBPL6 (P-value=6.36 × 10(-7)) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value=4.76 × 10(-7); rs62400067, P-value=3.54 × 10(-7)). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance.Molecular Psychiatry advance online publication, 2 February 2016; doi:10.1038/mp.2015.218.",
author = "C Herold and Hooli, {B V} and K Mullin and T Liu and Roehr, {J T} and M Mattheisen and Parrado, {A R} and L Bertram and C Lange and Tanzi, {R E}",
year = "2016",
month = feb,
day = "2",
doi = "10.1038/mp.2015.218",
language = "English",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3

AU - Herold, C

AU - Hooli, B V

AU - Mullin, K

AU - Liu, T

AU - Roehr, J T

AU - Mattheisen, M

AU - Parrado, A R

AU - Bertram, L

AU - Lange, C

AU - Tanzi, R E

PY - 2016/2/2

Y1 - 2016/2/2

N2 - The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1, and PSEN2 cause a subset of early-onset familial AD. On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ɛ4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study, we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3500 subjects from 1070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value=3.98 × 10(-8)), rs1347297 in the gene OSBPL6 (P-value=4.53 × 10(-8)), and rs1513625 near PDCL3 (P-value=4.28 × 10(-8)). In addition, rs72953347 in OSBPL6 (P-value=6.36 × 10(-7)) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value=4.76 × 10(-7); rs62400067, P-value=3.54 × 10(-7)). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance.Molecular Psychiatry advance online publication, 2 February 2016; doi:10.1038/mp.2015.218.

AB - The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1, and PSEN2 cause a subset of early-onset familial AD. On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ɛ4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study, we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3500 subjects from 1070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value=3.98 × 10(-8)), rs1347297 in the gene OSBPL6 (P-value=4.53 × 10(-8)), and rs1513625 near PDCL3 (P-value=4.28 × 10(-8)). In addition, rs72953347 in OSBPL6 (P-value=6.36 × 10(-7)) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value=4.76 × 10(-7); rs62400067, P-value=3.54 × 10(-7)). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance.Molecular Psychiatry advance online publication, 2 February 2016; doi:10.1038/mp.2015.218.

U2 - 10.1038/mp.2015.218

DO - 10.1038/mp.2015.218

M3 - Journal article

C2 - 26830138

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

ER -