The association of mitochondrial DNA haplogroups with POAG in African Americans

Abstract

Mitochondrial dysfunction has been implicated in the pathogenesis of primary open-angle glaucoma (POAG). However, the potential significance of mitochondrial DNA (mtDNA) haplogroups to POAG has not been evaluated in the overaffected African American population. To investigate the association of mtDNA haplogroups with POAG and its phenotypic characteristics, genotyping data from 4081 African American subjects (1919 cases and 2162 controls) was analyzed using 1293 positions on mtDNA. The overall frequency of mtDNA haplogroups in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study cohort was 37% L3, 29% L2, 21% L1, 4% L0, and 10% non-African haplogroups (non-L). When all haplogroups (L0, L1, L2, and non-L) were compared against theL3 reference group, after adjusting by age and principal component of ancestry, the non-L3 haplogroups showed higher risk of POAG (OR-1.19, p=0.02), with a particularly strong association among males (OR=1.41, p=0.003). More specifically the non-L group was associated with higher POAG risk than the L3 haplogroup (OR=1.77, p=0.007, Bonferroni adjusted p=0.027) and to the L3e (n=256, OR=1.92, p=0.007, Bonferroni adjusted p=0.029). No significant association was found when genders were analyzed together or in female only analysis. There were no significant differences in various POAG endophenotypes across mtDNA haplogroups. This study expands our knowledge of mitochondrial genetics and mtDNA haplogroup associations in African American POAG. Further work is needed to better understand the functional role of mtDNA polymorphisms and their interactions with nuclear genes that affect POAG.

Interactions between cytoplasmic and nuclear genomes confer sex‐specific effects on lifespan in Drosophila melanogaster

“…We predicted that any cyto-nuclear incompatibilities that manifest upon experimental disruption of coevolved cyto-nuclear genotypes might exhibit signatures of male-bias. This prediction is based on the hypothesis that maternal inheritance of the mitochondrial genome will facilitate the accumulation of mutations that are male-harming, but benign or beneficial to females (Frank & Hurst, 1996;Gemmell et al, 2004;Beekman et al, 2014;Dowling & Adrian, 2019); an evolutionary prediction that has received some empirical support from recent studies in D. melanogaster (Camus et al, 2012;Innocenti et al, 2011;Patel et al, 2016;Drummond et al, 2019;Nagarajan-Radha et al, 2019 in-press), hares (Smith et al, 2010), and humans (Martikainen et al, 2017;Milot et al, 2017;Gudiseva et al, 2019).…”

Interactions between cytoplasmic and nuclear genomes confer sex-specific effects on lifespan inDrosophila melanogaster

“…These genetic differences might underlie the phenotypic differences we observed, 593 however it's difficult to confirm such a possibility in the present study. 2019); an evolutionary prediction that has received some empirical support from recent studies 600 in D. melanogaster (Camus et al, 2012;Innocenti et al, 2011;Patel et al, 2016;Camus & 601 Dowling, 2018;Drummond et al, 2019;Nagarajan-Radha et al, 2019 in-press), hares (Smith 602 et al, 2010), and humans (Martikainen et al, 2017;Milot et al, 2017;Gudiseva et al, 2019). 603 We found no consistent evidence that mismatching of population-specific cytoplasmic and 604 nuclear genotypes results in a decrease in lifespan in either of the sexes.…”

Mitochondrial Haplogroup Association with Fasting Glucose Response in African Americans Treated with a Thiazide Diuretic

“…Haplogroups were obtained for each individual using HaploGrep, 29, 30 an open-source maternal haplogroup classifier. According to the recommendation from HaploGrep’s developer, we removed a total of 704 samples due to call discrepancy with the classified haplogroup HV, H2, and Z7.…”