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FPS has failed to show evidence of heritability, raising concerns. However, metrics used to index FPS\u2014and, importantly, other conditional phenotypes that are dependent on a baseline\u2014may not be suitable for the approaches used in genetic epidemiology studies. Here, we evaluated multiple metrics of FPS in a population\u2010based sample of preadolescent twins (<jats:italic>N<\/jats:italic>\u00a0=\u00a0569 from 320 twin pairs, <jats:italic>M<\/jats:italic><jats:sub>age<\/jats:sub> = 11.4) who completed a fear\u2010conditioning paradigm with airpuff\u2010elicited SR on two occasions (~1\u00a0month apart). We applied univariate and multivariate biometric modeling to estimate the heritability of FPS using several proposed standardization procedures. This was extended with data simulations to evaluate biases in heritability estimates of FPS (and similar metrics) under various scenarios. Consistent with previous studies, results indicated moderate test\u2010retest reliability (<jats:italic>r <\/jats:italic>= 0.59) and heritability of the overall SR (<jats:italic>h<jats:sup>2 <\/jats:sup><\/jats:italic>= 34%) but poor reliability and virtually no unique genetic influences on FPS when considering a raw or standardized differential score that removes baseline SR. Simulations demonstrated that the use of differential scores introduces bias in heritability estimates relative to jointly analyzing baseline SR and FPS in a multivariate model. However, strong dependency of FPS on baseline levels makes unique genetic influences virtually impossible to detect regardless of methodology. These findings indicate that FPS and other conditional phenotypes may not be well suited to serve as endophenotypes unless such codependency can be disentangled.<\/jats:p>","DOI":"10.1111\/psyp.13325","type":"journal-article","created":{"date-parts":[[2019,1,7]],"date-time":"2019-01-07T02:40:01Z","timestamp":1546828801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Fear\u2010potentiated startle response as an endophenotype: Evaluating metrics and methods for genetic applications"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2034-8341","authenticated-orcid":false,"given":"Jeanne E.","family":"Savage","sequence":"first","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee A.","family":"Moore","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea K.","family":"Sawyers","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Bourdon","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Verhulst","sequence":"additional","affiliation":[{"name":"Department of Psychology Michigan State University East Lansing Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dever M.","family":"Carney","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Moroney","sequence":"additional","affiliation":[{"name":"Emotion and Development Branch National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Machlin","sequence":"additional","affiliation":[{"name":"Emotion and Development Branch National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oumaima","family":"Kaabi","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0657-5257","authenticated-orcid":false,"given":"Scott","family":"Vrana","sequence":"additional","affiliation":[{"name":"Department of Psychology Virginia Commonwealth University Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Grillon","sequence":"additional","affiliation":[{"name":"Section on Neurobiology of Fear and Anxiety National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Brotman","sequence":"additional","affiliation":[{"name":"Emotion and Development Branch National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Leibenluft","sequence":"additional","affiliation":[{"name":"Emotion and Development Branch National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Pine","sequence":"additional","affiliation":[{"name":"Emotion and Development Branch National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxann","family":"Roberson\u2010Nay","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia"},{"name":"Department of Psychiatry Virginia Commonwealth University Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Hettema","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia"},{"name":"Department of Psychiatry Virginia Commonwealth University Richmond 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