{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T19:57:58Z","timestamp":1688587078871},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Preterm delivery (PTD) is the leading cause of neonatal mortality worldwide, yet its etiology remains largely unexplained. We propose that the genetic factors controlling this trait could act in a nonuniform manner during pregnancy, with each factor having a unique \u201cwindow of sensitivity.\u201d We test this hypothesis by modeling the distribution of gestational ages (GAs) observed in maternal cousins from the Swedish Medical Birth Register (MBR) (n = 35,541 pairs). The models were built using a time-to-event framework, with simulated genetic factors that increase the hazard of birth either uniformly across the pregnancy (constant effect) or only in particular windows (varying effect). By including various combinations of these factors, we obtained four models that were then optimized and compared. Best fit to the clinical data was observed when most of the factors had time-variant effects, independently of the number of loci simulated. Finally, power simulations were performed to assess the ability to discover varying-effect loci by usual methods for genome-wide association testing. We believe that the tools and concepts presented here should prove useful for the design of future studies of PTD and provide new insights into the genetic architecture determining human GA.<\/jats:p>","DOI":"10.1534\/g3.116.038612","type":"journal-article","created":{"date-parts":[[2017,3,2]],"date-time":"2017-03-02T02:10:42Z","timestamp":1488420642000},"page":"1349-1356","source":"Crossref","is-referenced-by-count":6,"title":["Time-Variant Genetic Effects as a Cause for Preterm Birth: Insights from a Population of Maternal Cousins in Sweden"],"prefix":"10.1093","volume":"7","author":[{"given":"Julius","family":"Juodakis","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 416 85, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Bacelis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sahlgrenska University Hospital \u00d6stra, 416 85 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Human Genetics Division, Cincinnati Children\u2019s Hospital Medical Center, Ohio 45229"},{"name":"Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children\u2019s Hospital Medical Center, Ohio 45229"},{"name":"March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio 45229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis J","family":"Muglia","sequence":"additional","affiliation":[{"name":"Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children\u2019s Hospital Medical Center, Ohio 45229"},{"name":"March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio 45229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Jacobsson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 416 85, Sweden"},{"name":"Department of Genetics and Bioinformatics, Area of Health Data and Digitalisation, Norwegian Institute of Public Health, 0473 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,4,1]]},"reference":[{"key":"2021042013194757200_bib1","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1093\/aje\/kwp001","article-title":"Maternal urinary metabolites of di-(2-ethylhexyl) phthalate in relation to the timing of labor in a US multicenter pregnancy cohort study.","volume":"169","author":"Adibi","year":"2009","journal-title":"Am. 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