TY - JOUR
T1 - Selection scan in Native Americans of Mexico identifies FADS2 rs174616
T2 - Evidence of gene-diet interactions affecting lipid levels and Delta-6-desaturase activity
AU - Romero-Hidalgo, Sandra
AU - Sagaceta-Mejía, Janine
AU - Villalobos-Comparán, Marisela
AU - Tejero, María Elizabeth
AU - Domínguez-Pérez, Mayra
AU - Jacobo-Albavera, Leonor
AU - Posadas-Sánchez, Rosalinda
AU - Vargas-Alarcón, Gilberto
AU - Posadas-Romero, Carlos
AU - Macías-Kauffer, Luis
AU - Vadillo-Ortega, Felipe
AU - Contreras-Sieck, Miguel Angel
AU - Acuña-Alonzo, Víctor
AU - Barquera, Rodrigo
AU - Macín, Gastón
AU - Binia, Aristea
AU - Guevara-Chávez, Jose Guadalupe
AU - Sebastián-Medina, Leticia
AU - Menjívar, Martha
AU - Canizales-Quinteros, Samuel
AU - Carnevale, Alessandra
AU - Villarreal-Molina, Teresa
N1 - Publisher Copyright:
© 2024
PY - 2024/8/15
Y1 - 2024/8/15
N2 - Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.
AB - Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.
UR - http://www.scopus.com/inward/record.url?scp=85200206273&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2024.e35477
DO - 10.1016/j.heliyon.2024.e35477
M3 - Journal articles
AN - SCOPUS:85200206273
SN - 2405-8440
VL - 10
JO - Heliyon
JF - Heliyon
IS - 15
M1 - e35477
ER -
