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 & 2 others John R. Attia, Perminder S. Sachdev

*Corresponding author for this work

Research output: Contribution to journalArticle

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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 languageEnglish
Article number23675
Pages (from-to)1-9
Number of pages9
JournalScientific Reports
Publication statusPublished - 31 Mar 2016
Externally publishedYes

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