Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults

Karen A. Mather; Anbupalam Thalamuthu; Christopher Oldmeadow; Fei Song; Nicola J. Armstrong; Anne Poljak; Elizabeth G. Holliday; Mark McEvoy; John B. Kwok; Amelia A. Assareh; Simone Reppermund; Nicole A. Kochan; Teresa Lee; David Ames; Margaret J. Wright; Julian N. Trollor; Peter W. Schofield; Henry Brodaty; Rodney J. Scott; Peter R. Schofield; John R. Attia; Perminder S. Sachdev

doi:10.1038/srep23675

Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults

Karen A. Mather^*, Anbupalam Thalamuthu, Christopher Oldmeadow, Fei Song, Nicola J. Armstrong, Anne Poljak, Elizabeth G. Holliday, Mark McEvoy, John B. Kwok, Amelia A. Assareh, Simone Reppermund, Nicole A. Kochan, Teresa Lee, David Ames, Margaret J. Wright, Julian N. Trollor, Peter W. Schofield, Henry Brodaty, Rodney J. Scott, Peter R. SchofieldJohn R. Attia, Perminder S. Sachdev

^*Corresponding author for this work

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Abstract

Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been associated with negative health outcomes. ApoH levels have high heritability. We undertook a genome-wide association study of ApoH levels using the largest sample to date and replicated the results in an independent cohort (total N = 1,255). In the discovery phase, a meta-analysis of two cohorts, the Sydney Memory and Ageing Study (Sydney MAS) and the Older Australian Twins Study (OATS) (n = 942) revealed genome-wide significant results in or near the APOH gene on chromosome 17 (top SNP, rs7211380, p = 1 × 10^-11). The results were replicated in an independent cohort, the Hunter Community Study (p < 0.002) (n = 313). Conditional and joint analysis (COJO) confirmed the association of the chromosomal 17 region with ApoH levels. The set of independent SNPs identified by COJO explained 23% of the variance. The relationships between the top SNPs and cardiovascular/lipid/cognition measures and diabetes were assessed in Sydney MAS, with suggestive results observed for diabetes and cognitive performance. However, replication of these results in the smaller OATS cohort was not found. This work provides impetus for future research to better understand the contribution of genetics to ApoH levels and its possible impacts on health.

Original language	English
Article number	23675
Pages (from-to)	1-9
Number of pages	9
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep23675
Publication status	Published - 31 Mar 2016
Externally published	Yes

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Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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Mather, K. A., Thalamuthu, A., Oldmeadow, C., Song, F., Armstrong, N. J., Poljak, A., Holliday, E. G., McEvoy, M., Kwok, J. B., Assareh, A. A., Reppermund, S., Kochan, N. A., Lee, T., Ames, D., Wright, M. J., Trollor, J. N., Schofield, P. W., Brodaty, H., Scott, R. J., ... Sachdev, P. S. (2016). Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults. Scientific Reports, 6, 1-9. [23675]. https://doi.org/10.1038/srep23675

@article{04e389206ddf44c4974cce6d90fe9f1d,

title = "Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults",

abstract = "Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been associated with negative health outcomes. ApoH levels have high heritability. We undertook a genome-wide association study of ApoH levels using the largest sample to date and replicated the results in an independent cohort (total N = 1,255). In the discovery phase, a meta-analysis of two cohorts, the Sydney Memory and Ageing Study (Sydney MAS) and the Older Australian Twins Study (OATS) (n = 942) revealed genome-wide significant results in or near the APOH gene on chromosome 17 (top SNP, rs7211380, p = 1 × 10-11). The results were replicated in an independent cohort, the Hunter Community Study (p < 0.002) (n = 313). Conditional and joint analysis (COJO) confirmed the association of the chromosomal 17 region with ApoH levels. The set of independent SNPs identified by COJO explained 23% of the variance. The relationships between the top SNPs and cardiovascular/lipid/cognition measures and diabetes were assessed in Sydney MAS, with suggestive results observed for diabetes and cognitive performance. However, replication of these results in the smaller OATS cohort was not found. This work provides impetus for future research to better understand the contribution of genetics to ApoH levels and its possible impacts on health.",

author = "Mather, {Karen A.} and Anbupalam Thalamuthu and Christopher Oldmeadow and Fei Song and Armstrong, {Nicola J.} and Anne Poljak and Holliday, {Elizabeth G.} and Mark McEvoy and Kwok, {John B.} and Assareh, {Amelia A.} and Simone Reppermund and Kochan, {Nicole A.} and Teresa Lee and David Ames and Wright, {Margaret J.} and Trollor, {Julian N.} and Schofield, {Peter W.} and Henry Brodaty and Scott, {Rodney J.} and Schofield, {Peter R.} and Attia, {John R.} and Sachdev, {Perminder S.}",

note = "Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2016",

month = mar,

day = "31",

doi = "10.1038/srep23675",

language = "English",

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Mather, KA, Thalamuthu, A, Oldmeadow, C, Song, F, Armstrong, NJ, Poljak, A, Holliday, EG, McEvoy, M, Kwok, JB, Assareh, AA, Reppermund, S, Kochan, NA, Lee, T, Ames, D, Wright, MJ, Trollor, JN, Schofield, PW, Brodaty, H, Scott, RJ, Schofield, PR, Attia, JR & Sachdev, PS 2016, 'Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults', Scientific Reports, vol. 6, 23675, pp. 1-9. https://doi.org/10.1038/srep23675

TY - JOUR

T1 - Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults

AU - Mather, Karen A.

AU - Thalamuthu, Anbupalam

AU - Oldmeadow, Christopher

AU - Song, Fei

AU - Armstrong, Nicola J.

AU - Poljak, Anne

AU - Holliday, Elizabeth G.

AU - McEvoy, Mark

AU - Kwok, John B.

AU - Assareh, Amelia A.

AU - Reppermund, Simone

AU - Kochan, Nicole A.

AU - Lee, Teresa

AU - Ames, David

AU - Wright, Margaret J.

AU - Trollor, Julian N.

AU - Schofield, Peter W.

AU - Brodaty, Henry

AU - Scott, Rodney J.

AU - Schofield, Peter R.

AU - Attia, John R.

AU - Sachdev, Perminder S.

N1 - Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2016/3/31

Y1 - 2016/3/31

N2 - Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been associated with negative health outcomes. ApoH levels have high heritability. We undertook a genome-wide association study of ApoH levels using the largest sample to date and replicated the results in an independent cohort (total N = 1,255). In the discovery phase, a meta-analysis of two cohorts, the Sydney Memory and Ageing Study (Sydney MAS) and the Older Australian Twins Study (OATS) (n = 942) revealed genome-wide significant results in or near the APOH gene on chromosome 17 (top SNP, rs7211380, p = 1 × 10-11). The results were replicated in an independent cohort, the Hunter Community Study (p < 0.002) (n = 313). Conditional and joint analysis (COJO) confirmed the association of the chromosomal 17 region with ApoH levels. The set of independent SNPs identified by COJO explained 23% of the variance. The relationships between the top SNPs and cardiovascular/lipid/cognition measures and diabetes were assessed in Sydney MAS, with suggestive results observed for diabetes and cognitive performance. However, replication of these results in the smaller OATS cohort was not found. This work provides impetus for future research to better understand the contribution of genetics to ApoH levels and its possible impacts on health.

AB - Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been associated with negative health outcomes. ApoH levels have high heritability. We undertook a genome-wide association study of ApoH levels using the largest sample to date and replicated the results in an independent cohort (total N = 1,255). In the discovery phase, a meta-analysis of two cohorts, the Sydney Memory and Ageing Study (Sydney MAS) and the Older Australian Twins Study (OATS) (n = 942) revealed genome-wide significant results in or near the APOH gene on chromosome 17 (top SNP, rs7211380, p = 1 × 10-11). The results were replicated in an independent cohort, the Hunter Community Study (p < 0.002) (n = 313). Conditional and joint analysis (COJO) confirmed the association of the chromosomal 17 region with ApoH levels. The set of independent SNPs identified by COJO explained 23% of the variance. The relationships between the top SNPs and cardiovascular/lipid/cognition measures and diabetes were assessed in Sydney MAS, with suggestive results observed for diabetes and cognitive performance. However, replication of these results in the smaller OATS cohort was not found. This work provides impetus for future research to better understand the contribution of genetics to ApoH levels and its possible impacts on health.

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JO - Scientific Reports

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ER -

Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults

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