PT  - JOURNAL ARTICLE
AU  - Matthew T. Buckley
AU  - Fernando Racimo
AU  - Morten E. Allentoft
AU  - Majken K. Jensen
AU  - Anna Jonsson
AU  - Hongyan Huang
AU  - Farhad Hormozdiari
AU  - Martin Sikora
AU  - Davide Marnetto
AU  - Eleazar Eskin
AU  - Marit E. Jørgensen
AU  - Niels Grarup
AU  - Oluf Pedersen
AU  - Torben Hansen
AU  - Peter Kraft
AU  - Eske Willerslev
AU  - Rasmus Nielsen
TI  - Selection on the FADS region in Europeans
AID  - 10.1101/086439
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 086439
4099  - http://biorxiv.org/content/early/2016/11/08/086439.short
4100  - http://biorxiv.org/content/early/2016/11/08/086439.full
AB  - FADS genes encode fatty acid desaturases that are important for the conversion of short chain polyunsaturated fatty acids (PUFAs) to long chain fatty acids. Prior studies indicate that the FADS genes have been subjected to strong positive selection in Africa, South Asia, Greenland, and Europe. By comparing FADS sequencing data from present-day and Bronze Age (5-3k years ago) Europeans, we identify possible targets of selection in the European population, which suggest that selection has targeted different alleles in the FADS genes in Europe than it has in South Asia or Greenland. The alleles showing the strongest changes in allele frequency since the Bronze Age show associations with expression changes and multiple lipid-related phenotypes. Furthermore, the selected alleles are associated with a decrease in linoleic acid and an increase in arachidonic and eicosapentaenoic acids among Europeans; this is an opposite effect of that observed for selected alleles in Inuit from Greenland. We show that multiple SNPs in the region affect expression levels and PUFA synthesis. Additionally, we find evidence for a gene-environment interaction influencing low-density lipoprotein (LDL) levels between alleles affecting PUFA synthesis and PUFA dietary intake: carriers of the selected, derived allele have diminished increases in LDL cholesterol with a higher intake of PUFAs. We hypothesize that the selective patterns observed in Europeans were driven by a change in dietary composition of fatty acids following the transition to agriculture, resulting in a lower intake of arachidonic acid and eicosapentaenoic acid, but a higher intake of linoleic acid and α-linolenic acid.