title: Genetic variants influencing biomarkers of nutrition are not associated with cognitive capability in middle-aged and older adults.
abstract: Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and β-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled β on Z-score for carriers vs. noncarriers: -0.05 (95% CI: -0.09, -0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D-raising allele of rs2282679 [pooled β per T allele: -0.03 (95% CI: -0.05, -0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK. tamuno.alfred@bristol.ac.uk
authors.forename: Tamuno
authors.initials: T
authors.lastname: Alfred
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.forename: Rachel
authors.initials: R
authors.lastname: Cooper
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hardy
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: Jane
authors.initials: J
authors.lastname: Elliott
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.forename: Elina
authors.initials: E
authors.lastname: Hyppönen
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Jane
authors.initials: J
authors.lastname: Maddock
authors.forename: Chris
authors.initials: C
authors.lastname: Power
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: Diana
authors.initials: D
authors.lastname: Kuh
authors.forename: Ian N M
authors.initials: IN
authors.lastname: Day
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000097:blood / Q000235:genetics; D005260:Female; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D018977:Micronutrients / Q000097:blood*; D008875:Middle Aged; D009752:Nutritional Status / Q000235:genetics*; D011110:Polymorphism, Genetic; D006113:United Kingdom; D014807:Vitamin D / Q000097:blood / Q000235:genetics; D014809:Vitamin D-Binding Protein / Q000235:genetics
chemical_list: D015415:Biomarkers; D018977:Micronutrients; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D007501:Iron