Mendelian randomization shows sex-specific associations between long-chain PUFA-related genotypes and cognitive performance in Danish schoolchildren

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DOI

  • Lotte Lauritzen, University of Copenhagen
  • ,
  • Louise B. Sorensen, University of Copenhagen
  • ,
  • Laurine B. Harslof, University of Copenhagen
  • ,
  • Christian Ritz, University of Copenhagen
  • ,
  • Ken D. Stark, Univ Waterloo, University of Waterloo, Dept Kinesiol
  • ,
  • Arne Astrup, University of Copenhagen
  • ,
  • Camilla B. Dyssegaard
  • ,
  • Niels Egelund
  • Kim F. Michaelsen, University of Copenhagen
  • ,
  • Camilla T. Damsgaard, University of Copenhagen

Background: Dietary and endogenously formed long-chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to improve cognitive development, but results are inconclusive, with suggestions of sex specificity. One study suggested that single-nucleotide polymorphisms (SNPs) rs1535 and rs174448 in the fatty acid desaturase (FADS) gene cluster have opposite effects on erythrocyte LCPUFAs at 9 mo.

Objective: To explore whether SNPs in FADS and elongase (ELOVL) genes were associated with school performance in a sex-specific manner, we performed a Mendelian randomization study using data from the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study with 765 Danish schoolchildren 8-11 y old.

Design: Associations between selected FADS1/2 SNPs (rs1535, rs174448, and rs174468) and ELOVL5 rs2397142, whole-blood fatty acid composition, and performance in the d2 Test of Attention and a reading test were analyzed in multiple regression models including all SNPs, SNP-sex interactions, and covariates related to testing conditions.

Results: FADS, rs1535 minor allele carriage associated with lower whole-blood arachidonic acid (P <0.002), and minor alleles of rs174448 tended to associate with lower docosahexaenoic acid (DHA) (P = 0.052). We identified sex interactions in 50% of the SNP performance sets. Sex-dependent associations were observed for rs174448 and rs1535 on the d2 Test of Attention outcomes (P <0.03) and for the associations between reading scores and rs174448 and rs2397142 (P <0.01). All of the sex-specific analyses showed associations in opposite directions in girls and boys. The minor allele carriage of rs174448 was associated with lower d2 Test of Attention performance (P <0.02) and reading scores (P <0.001) in boys but with better reading scores in girls (P

Conclusions: This study showed associations between rs1535 minor allele homozygosity and rs174448 major allele carriage and improved performance in 8- to 11-y-old boys but not in girls, thereby counter-acting existing sex differences. This may be a consequence of increased endogenous DHA synthesis in infancy but not at school-age.

Original languageEnglish
JournalAmerican Journal of Clinical Nutrition
Volume106
Issue1
Pages (from-to)88-95
Number of pages8
ISSN0002-9165
DOIs
Publication statusPublished - 1 Jul 2017

    Research areas

  • n-3 fatty acids, FADS, ELOVL, neurodevelopment, school performance, FATTY-ACID-METABOLISM, OPUS SCHOOL MEAL, DOCOSAHEXAENOIC ACID, FADS2 POLYMORPHISMS, CONTROLLED-TRIAL, NEURODEVELOPMENTAL OUTCOMES, DHA SUPPLEMENTATION, NORDIC DIET, FISH INTAKE, PREGNANCY

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