Study Looks at a New Method for Filtering Results from Genetic Studies Essay
Study Looks at a New Method for Filtering Results from Genetic Studies, Based on Inheritance Patterns Across Women of Different Racial and Ethnic Populations, in Order to Further Determine Risk of Preterm Birth
LAS VEGAS (Jan. 23, 2017)—In a study to be presented Thursday, Jan. 26, in the oral concurrent session at 1:15 p.m. PST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting™, researchers verified genetic results from one large study of women with spontaneous preterm birth, and highlighted 13 key genes in both mothers and babies which may be involved in preterm birth while also identifying 123 genes as top candidates for further study.
Tracy Manuck, M.D., associate professor of Maternal Fetal Medicine and medical director of the University of North Carolina Prematurity Prevention Clinic at the University of North Carolina-Chapel Hill, is the lead researcher and presenter of the study titled Use of evolutionary triangulation to refine genetic association studies of spontaneous preterm birth (SPTB). Manuck has been working to understand which genes influence why some women deliver preterm but others do not.
Nearly half a million babies are born too soon each year in the U.S. Preterm birth (before 37 weeks of pregnancy), is the leading cause of newborn death and babies who survive an early birth often face the risk of lifetime health challenges such as breathing problems, cerebral palsy, intellectual disabilities and others. Even babies born just a few weeks early have higher rates of hospitalization and illness than full-term infants. It is a serious health problem that costs the U.S. more than $26 billion annually.
“Although many genetic studies of preterm birth have been conducted, results have been inconsistent across populations,” said Manuck. She hopes to use a new method for filtering results from genetic studies, based on inheritance patterns across women of different ancestry, in order to fine-tune results from other genetic studies of preterm birth. This technique, termed “evolutionary triangulation,” relies on the fact that the rates of preterm birth vary significantly by race. In the United States, black women are almost twice as likely to deliver preterm as white women.
In addition to highlighting 13 key genes in mothers and babies which may be involved in preterm birth, Dr. Manuck and colleagues also examined 640 genes from an online preterm birth genetic database and, using the evolutionary triangulation technique, highlighted 123 additional genes as top candidates for further study. “These results have great potential implications for future studies to identify women at highest risk for spontaneous preterm birth,” Manuck stated. “Evolutionary triangulation is an exciting new way of thinking about genetic data, and one day may be applied to other disorders of pregnancy disproportionately affecting different populations of women.”
Abstract #11 Use of evolutionary triangulation to refine genetic association studies of spontaneous preterm birth (SPTB)
Tracy A. Manuck1, Minjun Huang2, Louis Muglia3, Scott M. Williams4 1University of North Carolina – Chapel Hill, Chapel Hill, NC, 2Dartmouth College, Hanover, NH, 3Cincinnati Children’s Hospital, Cincinnati, OH, 4Case Western Reserve University, Cleveland, OH
Objective: Genetic association studies of SPTB have generally yielded inconsistent results. SPTB rates in the US are lowest in European-Americans compared to other groups including Hispanics, American Indians, and African-Americans. We hypothesized that genes identified by Evolutionary Triangulation (ET), a novel analytic technique exploiting evolutionary differentiation by comparing population structure among 3 populations with variable patterns of disease prevalence, could refine results from previous SPTB gene association studies.
Study Design: We tested 2 SPTB gene lists: (1) Top maternal and fetal genes corresponding to top 20 maternal and fetal SNPs from GWAS of 1,025 SPTB cases < 34 wks and 1,015 term controls (Zhang, et al., 2015) (2) 640 genes on online dbPTB site. To generate the ET gene list, SNP allele frequency data were first obtained from CEU (Utah residents with Western and Northern European ancestry from the CEPH collection), GIH (Gujarati Indians in Houston, TX)/MEX (Mexican ancestry in Los Angeles, CA), and YRI (Yoruba in Ibadan, Nigeria)/ASW (African ancestry in Southwest USA) populations from HapMap. Next, we calculated Wright’s FST, a metric assessing population genetic differences by pairwise allele comparisons. ET SNPs were selected according to the overlaps of high and low FST with CEU as the outlier population across several degrees of differentiation. Genes ±100 Kb of each ET SNP were considered ET genes and were compared to SPTB genes from List 1 and List 2.
Results: ET identified 5/17 maternal and 8/16 fetal genes from Zhang (Table), several of which are expressed in the uterus (maternal) or placenta (fetal). Of 640 dbPTB genes, 79 were identified by CEU_GIH_YRI ET, and 57 were identified by the CEU_ASW_MEX ET gene list. In total, ET identified 123 unique genes of the 640 dbPTB genes (19.2%).
Conclusion: Applying ET analysis to SPTB provided independent support for multiple genes previously associated in GWAS and candidate gene studies, and presents an alternative filtering metric for genetic analyses based on evolutionary history. Genes identified in prior SPTB association studies confirmed by ET should be prioritized for further genetic prematurity research. Table. Genes from List 1 identified by ET. *gene expressed in uterus #gene expressed in placenta.