title: The heritability of brain metabolites on proton magnetic resonance spectroscopy in older individuals.
abstract: Twin studies have shown that many aspects of brain structure are heritable, suggesting a strong genetic contribution to brain structure. Less is known about functional aspects of the brain, in particular biologically relevant metabolites in the brain such as those measured by proton magnetic resonance spectroscopy (((1))H MRS), N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (ml), which have been suggested as possible markers of brain aging and early dementia. We examined 296 (56 male/108 female monozygotic and 43 male/89 female dizygotic) older twins (mean age 72.2 ± 5.5 years, range 65-88), for the levels of these metabolites relative to the H(2)O signal in the posterior cingulate cortex using ((1))H MRS. All metabolites showed substantial heritability, which was greatest for the neuronal integrity marker NAA (72%), and less so for the others - Cr (51%), Cho (33%) and ml (55%). The heritability of these markers did not change significantly with age or sex. The genetic determination of NAA, along with the evidence that NAA levels change in aging and neurodegenerative diseases suggest that it is a potential endophenotype of brain aging and dementia.
authors.affiliation: School of Psychiatry, University of New South Wales, 22-32 King Street, Building R1F, Randwick Campus, UNSW, Randwick, 2052, Sydney, Australia. sa.batouli@unsw.edu.au
authors.forename: Seyed Amir Hossein
authors.initials: SA
authors.lastname: Batouli
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.forename: Chao
authors.initials: C
authors.lastname: Suo
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.forename: Julian N
authors.initials: JN
authors.lastname: Trollor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000235:genetics; D001921:Brain / Q000502:physiology*; D002794:Choline / Q000032:analysis* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D011522:Protons; D014427:Twins
chemical_list: D005819:Genetic Markers; D011522:Protons; D001224:Aspartic Acid; C000179:N-acetylaspartate; D002794:Choline