2033 GENOME-WIDE ASSOCIATION STUDY IDENTIFIES CANDIDATE GENES FOR ABNORMAL SPERM MORPHOLOGY IN TWO COHORTS OF MEN

Abstract

You have accessJournal of UrologyInfertility: Basic Research, Physiology, Pathophysiology1 Apr 20132033 GENOME-WIDE ASSOCIATION STUDY IDENTIFIES CANDIDATE GENES FOR ABNORMAL SPERM MORPHOLOGY IN TWO COHORTS OF MEN James Hotaling, Gulum Kosova, Samuel Ohlander, Craig Niederberger, Gail S. Prins, and Carole Ober James HotalingJames Hotaling Chicago, IL More articles by this author , Gulum KosovaGulum Kosova Chicago, IL More articles by this author , Samuel OhlanderSamuel Ohlander Chicago, IL More articles by this author , Craig NiederbergerCraig Niederberger Chicago, IL More articles by this author , Gail S. PrinsGail S. Prins Chicago, IL More articles by this author , and Carole OberCarole Ober Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2452AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Despite numerous genes known to affect fertility in animal models, little is known about the contribution of individual genes to human fertility. We previously identified 9 genes associated with reduced fertility in a founder population and lower sperm count and motility in a validation cohort (Kosova et al. 2012; AJHG 90). Here we examine the effects of these genes on sperm morphology in the same validation cohort. METHODS We studied 269 married men from a founder population, the Hutterites, that proscribes contraception and has large family sizes for discovery of genes associated with family size and birth rate. Of the ∼250,000 autosomal single-nucleotide polymorphisms (SNPs) included in studies of male fertility traits, 41 SNPs with P < 1x10-4 were taken forward to a validation study of abnormal sperm morphology in 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Sperm morphology analyses were performed using Kruger strict criteria with %normal morphology considered as a continuous outcome variable, and normal or abnormal sperm morphology as a categorical variable. We tested associations between each of 41 SNPs and semen parameters using linear regression and Fisher's exact test, as appropriate; the direction of the effect for a given allele (increased or decreased fertility) was kept consistent with the initial association observed in the Hutterites. RESULTS Two SNPs, rs680730 (in DSCAML1) and rs10129954 (in DPF3), that were associated with fertility in Hutterite men were also associated with %normal sperm morphology in ethnically diverse Chicago men (P = 0.017 and 0.022, respectively). The C allele at rs680739 was also associated with abnormal sperm morphology when tested as a binary outcome (P=0.033). Further analyses with % of specific morphological abnormalities suggest that associations with these two markers may be due to sperm head defects. Interestingly, in our previous study these two variants were also associated with sperm motility parameters, including total motile sperm count, linearity and beat frequency. CONCLUSIONS We identified variants in two genes, DSCAML1 and DPF3, that code for proteins involved in stem cell selection and self-avoidance, and are associated with poor sperm morphology in our study. Future work in larger sample sizes will be needed to replicate these findings and to characterize their role in male reproductive processes. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e835 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Hotaling Chicago, IL More articles by this author Gulum Kosova Chicago, IL More articles by this author Samuel Ohlander Chicago, IL More articles by this author Craig Niederberger Chicago, IL More articles by this author Gail S. Prins Chicago, IL More articles by this author Carole Ober Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...