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MEs are interpreted as multivariate summaries of correlated gene\u2010expression patterns and network connectivity across genes within a module. As such, they have the potential to elucidate the mechanisms by which molecular genomic variation contributes to individual differences in complex traits. Although increasingly used to test for associations between modules and complex traits, the genetic and environmental etiology of MEs has not been empirically established. It is unclear if, and to what degree, individual differences in blood\u2010derived MEs reflect random variation versus familial aggregation arising from heritable or shared environmental influences. We used biometrical genetic analyses to estimate the contribution of genetic and environmental influences on MEs derived from blood lymphocytes collected on a sample of <jats:italic>N<\/jats:italic>\u2009=\u2009661 older male twins from the Vietnam Era Twin Study of Aging (VETSA) whose mean age at assessment was 67.7\u2009years (SD\u2009=\u20092.6\u2009years, range\u2009=\u200962\u201374\u2009years). Of the 26 detected MEs, 14 (56%) had statistically significant additive genetic variation with an average heritability of 44% (SD\u2009=\u20090.08, range\u2009=\u200935%\u201364%). Despite the relatively small sample size, this demonstration of significant family aggregation including estimates of heritability in 14 of the 26 MEs suggests that blood\u2010based MEs are reliable and merit further exploration in terms of their associations with complex traits and diseases.<\/jats:p>","DOI":"10.1002\/ajmg.b.33003","type":"journal-article","created":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T06:39:41Z","timestamp":1723271981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A twin analysis to estimate genetic and environmental factors contributing to variation in weighted gene co\u2010expression network module eigengenes"],"prefix":"10.1002","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8655-2823","authenticated-orcid":false,"given":"Nathan A.","family":"Gillespie","sequence":"first","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavior Genetics Virginia Commonwealth University  Virginia USA"},{"name":"QIMR Berghofer Medical Research Institute  Herston Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler R.","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego  La Jolla California USA"},{"name":"Center for Behavior Genetics of Aging University of California San Diego  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gentry C.","family":"Hearn","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences Boston University  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan L.","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences Boston University  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming T.","family":"Tsuang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Lyons","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences Boston University  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol E.","family":"Franz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego  La Jolla California USA"},{"name":"Center for Behavior Genetics of Aging University of California San Diego  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William S.","family":"Kremen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego  La Jolla California USA"},{"name":"Center for Behavior Genetics of Aging University of California San Diego  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Glatt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences SUNY Upstate Medical University  Syracuse New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02294359"},{"key":"e_1_2_11_3_1","unstructured":"Babraham Bioinformatics. 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