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Common genetic variation may mediate vulnerability to the insult of prematurity and provide opportunities to predict and modify risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To gain novel biological and therapeutic insights from the integrated analysis of magnetic resonance imaging and genetic data, informed by prior knowledge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We apply our previously validated pathway\u2010based statistical method and a novel network\u2010based method to discover sources of common genetic variation associated with imaging features indicative of structural brain damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lipid pathways were highly ranked by Pathways Sparse Reduced Rank Regression in a model examining the effect of prematurity, and <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content> (peroxisome proliferator\u2010activated receptor) signaling was the highest ranked pathway once degree of prematurity was accounted for. Within the <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content> pathway, five genes were found by Graph Guided Group Lasso to be highly associated with the phenotype: aquaporin 7 (<jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>7), malic enzyme 1, <jats:styled-content style=\"fixed-case\">NADP<\/jats:styled-content>(+)\u2010dependent, cytosolic (<jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content>1), perilipin 1 (<jats:styled-content style=\"fixed-case\">PLIN<\/jats:styled-content>1), solute carrier family 27 (fatty acid transporter), member 1 (<jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>27A1), and acetyl\u2010CoA acyltransferase 1 (<jats:styled-content style=\"fixed-case\">ACAA<\/jats:styled-content>1). Expression of four of these (<jats:styled-content style=\"fixed-case\">ACAA<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>7, <jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content>1, and <jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>27A1) is controlled by a common transcription factor, early growth response 4 (<jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>\u20104).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This suggests an important role for lipid pathways in influencing development of white matter in preterm infants, and in particular a significant role for interindividual genetic variation in <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content> signaling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.434","type":"journal-article","created":{"date-parts":[[2016,4,3]],"date-time":"2016-04-03T18:43:44Z","timestamp":1459709024000},"source":"Crossref","is-referenced-by-count":26,"title":["Possible relationship between common genetic variation and white matter development in a pilot study of preterm infants"],"prefix":"10.1002","volume":"6","author":[{"given":"Michelle L.","family":"Krishnan","sequence":"first","affiliation":[{"name":"Centre for the Developing Brain King's College London St Thomas' Hospital London SE1 7EH UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering King\u2018s College London St Thomas\u2018 Hospital London SE1 7EH UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Silver","sequence":"additional","affiliation":[{"name":"Department of Population Health London School of Hygiene and Tropical Medicine London WC1E 7HT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Boardman","sequence":"additional","affiliation":[{"name":"MRC Centre for Reproductive Health University of Edinburgh Edinburgh EH16 4TJ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Ball","sequence":"additional","affiliation":[{"name":"Centre for the Developing Brain King's College London St Thomas' Hospital London SE1 7EH UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena J.","family":"Counsell","sequence":"additional","affiliation":[{"name":"Centre for the Developing Brain King's College London St Thomas' Hospital London SE1 7EH UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Walley","sequence":"additional","affiliation":[{"name":"School of Public Health Faculty of Medicine Imperial College London Norfolk Place London W2 1PG UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Montana","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering King\u2018s College London St Thomas\u2018 Hospital London SE1 7EH UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony David","family":"Edwards","sequence":"additional","affiliation":[{"name":"Centre for the Developing Brain King's College London St Thomas' Hospital London SE1 7EH UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3233\/NPM-14814008","article-title":"Current trends and future challenges in neonatal parenteral nutrition","volume":"7","author":"Adamkin D. 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