A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program

BackgroundHeight has been associated with many clinical traits but whether such associations are causal versus secondary to confounding remains unclear in many cases. To systematically examine this question, we performed a Mendelian Randomization-Phenome-wide association study (MR-PheWAS) using clinical and genetic data from a national healthcare system biobank.Methods and findingsAnalyses were performed using data from the US Veterans Affairs (VA) Million Veteran Program in non-Hispanic White (EA, n = 222,300) and non-Hispanic Black (AA, n = 58,151) adults in the US. We estimated height genetic risk based on 3290 height-associated variants from a recent European-ancestry genome-wide meta-analysis. We compared associations of measured and genetically-predicted height with phenome-wide traits derived from the VA electronic health record, adjusting for age, sex, and genetic principal components. We found 345 clinical traits associated with measured height in EA and an additional 17 in AA. Of these, 127 were associated with genetically-predicted height at phenome-wide significance in EA and 2 in AA. These associations were largely independent from body mass index. We confirmed several previously described MR associations between height and cardiovascular disease traits such as hypertension, hyperlipidemia, coronary heart disease (CHD), and atrial fibrillation, and further uncovered MR associations with venous circulatory disorders and peripheral neuropathy in the presence and absence of diabetes. As a number of traits associated with genetically-predicted height frequently co-occur with CHD, we evaluated effect modification by CHD status of genetically-predicted height associations with risk factors for and complications of CHD. We found modification of effects of MR associations by CHD status for atrial fibrillation/flutter but not for hypertension, hyperlipidemia, or venous circulatory disorders.ConclusionsWe conclude that height may be an unrecognized but biologically plausible risk factor for several common conditions in adults. However, more studies are needed to reliably exclude horizontal pleiotropy as a driving force behind at least some of the MR associations observed in this study.     

Position of neck banded blenny Leptostichaeus pumilus (Perciformes: Zoarcoidei) in the system of the suborder Zoarcoidei as inferred from molecular genetic data

Molecular genetic study of genetic variations within COI, cytochrome b, and 16S rRNA of mitochondrial DNA in neck banded blenny Leptostichaeus pumilus, which was earlier assigned to the family Stichaeidae, indicates that the species is most close to a group combining the families Zoarcidae, Neozoarcidae, and Anarhichadidae. Significant genetic differences between neck banded blenny and the family Stichaeidae correspond to the level of divergence between other families of the suborder Zoarcoidei (Zaproridae, Ptilichthyidae, Pholidae, Cryptacanthodidae, and Bathymasteridae).     

Phylogenetic and taxonomic relationships of northern Far Eastern phoxinin minnows, Phoxinus and Rhynchocypris (Pisces, Cyprinidae), as inferred from allozyme and mitochondrial 16S rRNA sequence analyses

Analyses of allozyme (18 loci) and partial mitochondrial DNA (mtDNA) sequences (1295 bp, 16S rRNA) support the classification of phoxinin minnows from the northern Far East into 2 genera of 8 species: Phoxinus phoxinus, Rhynchocypris oxycephalus, R. perenurus, R. czekanowskii, R. kumgangensis, R. semotilus, R. lagowskii and R. sp. (bergi ?). Although R. lagowskii from Japan and the Amur basin and R. sp. from Vladivostok region to Korea have been classified into a single species by many authors as R. lagowskii, they form separate clusters in both analyses, suggesting different specific status. Some R. oxycephalus and R. perenurus had the mtDNA haplotypes of R. lagowskii and R. czekanowskii, respectively, which probably indicates that local introgression of mtDNA occurred through inter-specific hybridization. Rhynchocypris forms a monophyletic cluster with dace genera Tribolodon and Pseudaspius, not with Phoxinus. Eurasian and American Phoxinus are suggested to be paraphyletic.     

Nucleotide sequence variation of the mitochondrial COI gene in several eelpout species of the genus Zoarces (Zoarcidae, Pisces)

The mitochondrial COI gene was for the first time sequenced in eelpout species of the genus Zoarces from the Taui Bay of the Sea of Okhotsk: notched-fin Z. elongatus Kner, 1868 and the new sympatric form Zoarces sp., differing in a large set of morphological traits. The two species were compared with European eelpout Z. viviparus Linnaeus, 1758 from the Finnish Bay of the Baltic Sea. Divergence and phylogenetic analyses demonstrated a greater genetic similarity between Zoarces sp. and Z. viviparus than between sympatric Zoarces sp. and Z. elongatus.