2. Academic Validation
  3. Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults

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

  • Sci Rep. 2016 Mar 31;6:23675. doi: 10.1038/srep23675.
Karen A Mather 1,  Anbupalam Thalamuthu 1,  Christopher Oldmeadow 2,  Fei Song 1,  Nicola J Armstrong 1 3,  Anne Poljak 1 4 5,  Elizabeth G Holliday 2 6,  Mark McEvoy 2,  John B Kwok 7 5,  Amelia A Assareh 1,  Simone Reppermund 1 8,  Nicole A Kochan 1 9,  Teresa Lee 1 9,  David Ames 10 11,  Margaret J Wright 12,  Julian N Trollor 1 8,  Peter W Schofield 13,  Henry Brodaty 1 14,  Rodney J Scott 2,  Peter R Schofield 7 5,  John R Attia 2,  Perminder S Sachdev 1 9
Affiliations

Affiliations

  • 1 Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
  • 2 Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
  • 3 Mathematics and Statistics, Murdoch University, Perth, Australia.
  • 4 Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia.
  • 5 School of Medical Sciences, University of New South Wales, Sydney, Australia.
  • 6 Centre for Clinical Epidemiology &Biostatistics, University of Newcastle, Newcastle, Australia.
  • 7 Neuroscience Research Australia, Randwick, Australia.
  • 8 Department of Developmental Disability Neuropsychiatry, University of New South Wales, Sydney, Australia.
  • 9 Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, Australia.
  • 10 National Ageing Research Institute, Melbourne, Australia.
  • 11 Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, Australia.
  • 12 Queensland Brain Institute, University of Queensland, Brisbane, Australia.
  • 13 School of Medicine &Public Health, University of Newcastle, Newcastle, Australia.
  • 14 Dementia Collaborative Research Centre - Assessment and Better Care, University of New South Wales, Sydney, Australia.
PMID: 27030319 DOI: 10.1038/srep23675
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.

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