Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes
19 de mayo de 2022
Les invitamos a leer el reciente artículo: "Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes" donde participó el Dr. Andrés Moreno , profesor investigador de la UGA-Langebio. Dicho artículo fue publicado en AJHG.
Autores: Maria A. Nieves-Colón, Keyla M. Badillo Rivera, Karla Sandoval,Vanessa Villanueva Dávalos, Luis E. Enriquez Lencinas, Javier Mendoza-Revilla, Kaustubh Adhikari, Ram González-Buenfil, Jessica W. Chen, Elisa T. Zhang, Alexandra Sockell, Patricia Ortiz-Tello, Gloria Malena Hurtado, Ramiro Condori Salas, Ricardo Cebrecos, José C. Manzaneda Choque, Franz P. Manzaneda Choque, Germán P. Yábar Pilco, Erin Rawls, Celeste Eng, Scott Huntsman, Esteban Burchard, Andrés Ruiz-Linares, Rolando González-José, Gabriel Bedoya, Francisco Rothhammer, Maria Cátira Bortolini, Giovanni Poletti, Carla Gallo,Carlos D. Bustamante, Julie C. Baker, Christopher R. Gignoux, Genevieve L. Wojcik, and Andrés Moreno-Estrada.
Felicitamos al estudiantado y profesorado que contribuyeron en esta investigación por su arduo trabajo.
Abstract: Preeclampsia is a multi-organ complication of pregnancy characterized by sudden hypertension and proteinuria that is among the lead-ing causes of preterm delivery and maternal morbidity and mortality worldwide. The heterogeneity of preeclampsia poses a challenge for understanding its etiology and molecular basis. Intriguingly, risk for the condition increases in high-altitude regions such as the Peruvian Andes. To investigate the genetic basis of preeclampsia in a population living at high altitude, we characterized genome-wide variation in a cohort of preeclamptic and healthy Andean families (n ¼ 883) from Puno, Peru, a city located above 3,800 meters of altitude. Our study collected genomic DNA and medical records from case-control trios and duos in local hospital settings. We generated genotype data for
439,314 SNPs, determined global ancestry patterns, and mapped associations between genetic variants and preeclampsia phenotypes. A transmission disequilibrium test (TDT) revealed variants near genes of biological importance for placental and blood vessel function. The top candidate region was found on chromosome 13 of the fetal genome and contains clotting factor genes PROZ, F7, and F10. These
findings provide supporting evidence that common genetic variants within coagulation genes play an important role in preeclampsia. A selection scan revealed a potential adaptive signal around the ADAM12 locus on chromosome 10, implicated in pregnancy disorders. Our discovery of an association in a functional pathway relevant to pregnancy physiology in an understudied population of Native American origin demonstrates the increased power of family-based study design and underscores the importance of conducting genetic research in diverse populations.
Keywords:preeclampsia, pregnancy, Andean, Peru, PROZ, GWAS, family trio, offspring genome.