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.
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Mather
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Oldmeadow
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.|Mathematics and Statistics, Murdoch University, Perth, Australia.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Armstrong
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.|Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia.|School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.|Centre for Clinical Epidemiology &Biostatistics, University of Newcastle, Newcastle, Australia.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Holliday
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: McEvoy
authors.affiliation: Neuroscience Research Australia, Randwick, Australia.|School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Kwok
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Assareh
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.|Department of Developmental Disability Neuropsychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Simone
authors.initials: S
authors.lastname: Reppermund
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.|Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, Australia.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Kochan
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.|Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, Australia.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lee
authors.affiliation: National Ageing Research Institute, Melbourne, Australia.|Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.|Department of Developmental Disability Neuropsychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Julian N
authors.initials: JN
authors.lastname: Trollor
authors.affiliation: School of Medicine &Public Health, University of Newcastle, Newcastle, Australia.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Schofield
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.|Dementia Collaborative Research Centre - Assessment and Better Care, University of New South Wales, Sydney, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: Neuroscience Research Australia, Randwick, Australia.|School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Attia
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.|Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, Australia.
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000276:immunology; D001315:Australia; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D002886:Chromosomes, Human, Pair 17; D060825:Cognitive Dysfunction / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053482:beta 2-Glycoprotein I / Q000097:blood / Q000235:genetics*
chemical_list: D053482:beta 2-Glycoprotein I