Multiplex genomewide association analysis of breast milk fatty acid composition extends the phenotypic association and potential selection of FADS1 variants to arachidonic acid, a critical infant micronutrient
| Autor: | Mychaleckyj, J, Nayak, U, Colgate, E, Zhang, D, Carstensen, T, Ahmed, S, Ahmed, T, Mentzer, A, Alam, M, Kirkpatrick, B, Haque, R, Faruque, A, Petri, W |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Fatty Acid Desaturases
Arachidonic Acid fatty acid desaturase Genotype Milk Human Complex Traits Fatty Acids selection Infant Mothers Polymorphism Single Nucleotide Diet Delta-5 Fatty Acid Desaturase Phenotype genomewide association breast milk Humans Female Micronutrients Alleles Genome-Wide Association Study |
| Zdroj: | Journal of Medical Genetics |
| ISSN: | 1468-6244 0022-2593 |
| Popis: | Background Breast milk is the sole nutrition source during exclusive breastfeeding, and polyunsaturated fatty acids (FAs) are critical micronutrients in infant physical and cognitive development. There has been no prior genomewide association study of breast milk, hence our objective was to test for genetic association with breast milk FA composition. Methods We measured the fractional composition of 26 individual FAs in breast milk samples from three cohorts totalling 1142 Bangladeshi mothers whose infants were genotyped on the Illumina MEGA chip and replicated on a custom Affymetrix 30K SNP array (n=616). Maternal genotypes were imputed using IMPUTE. Results fter running 33 separate FA fraction phenotypes, we found that SNPs known to be associated with serum FAs in the FADS1/2/3 region were also associated with breast milk FA composition (experimentwise significance threshold 4.2×10^−9). Hypothesisneutral comparison of the 33 fractions showed that the most significant genetic association at the FADS1/2/3 locus was with fraction of arachidonic acid (AA) at SNP rs174556, with a very large per major allele effect size of 17% higher breast milk AA level. There was no evidence of independent association at FADS1/2/3 with any other FA or SNP after conditioning on AA and rs174556. We also found novel significant experiment-wise SNP associations with: polyunsaturated fatty acid (PUFA) 6/ PUFA3 ratio (sorting nexin 29), eicosenoic (intergenic) and capric (component of oligomeric Golgi complex 3) acids; and six additional loci at genomewide significance ( Conclusions is the primary FA in breast milk influenced by genetic variation at the FADS1/2/3 locus, extending the potential phenotypes under genetic selection to include breast milk composition, thereby possibly affecting infant growth or cognition. Breast milk FA composition is influenced by maternal genetics in addition to diet and body composition. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|