ORIGINAL ARTICLE Sudden Infant Death “Syndrome”—Insights and Future Directions From a Utah Population Database Analysis Erik D. Christensen, 1,2 Justin Berger, 3 Mouied M. Alashari, 4 Hilary Coon, 5 Cynthia Robison, 6 Hsu-Tso Ho, 7 David R. Adams, 7 Willian A. Gahl, 7 Ken R. Smith, 3 John M. Opitz, 4,8,9,10 and Dennis R. Johnson 4,7 * 1 Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 2 Office of the Medical Examiner, Utah Department of Health, Salt Lake City, Utah 3 Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 4 Division of Pediatric Pathology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 5 Department of Psychiatry, School of Medicine, University of Utah, Salt Lake City, Utah 6 Office of Vital Records and Statistics, Utah Department of Health, Salt Lake City, Utah 7 National Human Genome Research Institute, Undiagnosed Disease Program, NIH, Bethesda, Maryland 8 Department of Pediatrics (Medical Genetics), School of Medicine, University of Utah, Salt Lake City, Utah 9 Department of Obstetrics and Gynecology, School of Medicine, University of Utah, Salt Lake City, Utah 10 Department of Human Genetics, School of Medicine, University of Utah, Salt Lake City, Utah Manuscript Received: 21 June 2016; Manuscript Accepted: 19 September 2016 “Sudden Infant Death syndrome” (SIDS) represents the common- est category of infant death after the first month of life. As genome scale sequencing greatly facilitates the identification of new can- didate disease variants, the challenges of ascribing causation to these variants persists. In order to determine the extent to which SIDS occurs in related individuals and their pedigree structure we undertook an analysis of SIDS using the Utah Population Data- base, recording, for example, evidence of enrichment for genetic causation following the back-to-sleep recommendations of 1992 and 1994. Our evaluation of the pre- and post back-to-sleep incidence of SIDS in Utah showed a decrease in SIDS incidence on the order of eightfold following back-to-sleep. An odds ratio of 4.2 for SIDS recurrence among sibs was identified from 1968 to 2013 which was similar to the odds ratio of 4.84 for death due to other or unknown cause among sibs of SIDS cases for the same time period. Combining first through thid degree relatives yielded an odds ratio of SIDS recurrence of 9.29 in the post-back-to-sleep (1995–2013) subset of SIDS cases where similar calculations of first-third degree relatives for the entire time period of 1968–2013 showed an odds ratio of 2.95. Expanded multigenertional pedi- grees showing enrichment for SIDS were also identified. Based on these findings we hypothesize that post back-to-sleep SIDS, espe- cially recurrences within a family, are potentially enriched for genetic causes due to the impact of safe sleeping guidelines in mitigating environmental risk factors. Ó 2016 Wiley Periodicals, Inc. Key words: Sudden Infant Death syndrome; SIDS; Utah population database; familial SIDS; SIDS recurrence INTRODUCTION “Sudden Infant Death Syndrome” (SIDS) refers to a group of infants who died unexpectedly in the first year of life, apparently A portion of this work was presented in abstract forme at the Fall meeting of the Society for Pediatric Pathology, Toronto, ON, Canada, October 2015. Conflict of interest: None.  Correspondence to: Dennis R. Johnson, National Human Genome Research Institute, Undiagnosed Disease Program, NIH, NHGRI Building 50, 50 South Dr., Bethesda, MD. E-mail: dennis.johnson@nih.gov Article first published online in Wiley Online Library (wileyonlinelibrary.com): 00 Month 2016 DOI 10.1002/ajmg.a.37994 How to Cite this Article: Christensen ED, Berger J, Alashari MM, Coon H, Robison C, Ho H-T, Adams DR, Gahl WA, Smith KR, Opitz JM, Johnson DR. 2016. Sudden infant death “syndrome”—insights and future directions from a Utah population database analysis. Am J Med Genet Part A 9999A:1–6. Ó 2016 Wiley Periodicals, Inc. 1