{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:27:59Z","timestamp":1740130079646,"version":"3.37.3"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202802\/Z\/16\/Z"],"award-info":[{"award-number":["202802\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Avon Longitudinal Study for Parents and Children","award":["102215"],"award-info":[{"award-number":["102215"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["217065\/Z\/19\/Z"],"award-info":[{"award-number":["217065\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Glycosuria is a condition where glucose is detected in urine at higher concentrations than normal (i.e. not detectable). Glycosuria at some point during pregnancy has an estimated prevalence of 50% and is associated with adverse outcomes in both mothers and offspring. Little is currently known about the genetic contribution to this trait or the extent to which it overlaps with other seemingly related traits, e.g. diabetes. We performed a genome-wide association study (GWAS) for self-reported glycosuria in pregnant mothers from the Avon Longitudinal Study of Parents and Children (cases\/controls\u2009=\u20091249\/5140). We identified two loci, one of which (lead SNP\u2009=\u2009rs13337037; chromosome 16; odds ratio of glycosuria per effect allele: 1.42; 95% CI: 1.30, 1.56; P\u2009=\u20091.97\u2009\u00d7\u200910\u221213) was then validated using an obstetric measure of glycosuria measured in the same cohort (227\/6639). We performed a secondary GWAS in the 1986 Northern Finland Birth Cohort (NFBC1986; 747\/2991) using midwife-reported glycosuria and offspring genotype as a proxy for maternal genotype. The combined results revealed evidence for a consistent effect on glycosuria at the chromosome 16 locus. In follow-up analyses, we saw little evidence of shared genetic underpinnings with the exception of urinary albumin-to-creatinine ratio (Rg\u2009=\u20090.64; SE\u2009=\u20090.22; P\u2009=\u20090.0042), a biomarker of kidney disease. In conclusion, we identified a genetic association with self-reported glycosuria during pregnancy, with the lead SNP located 15kB upstream of SLC5A2, a target of antidiabetic drugs. The lack of strong genetic correlation with seemingly related traits such as type 2 diabetes suggests different genetic risk factors exist for glycosuria during pregnancy.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa054","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T12:09:31Z","timestamp":1585138171000},"page":"2098-2106","source":"Crossref","is-referenced-by-count":3,"title":["Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6262-3447","authenticated-orcid":false,"given":"Matthew A","family":"Lee","sequence":"first","affiliation":[{"name":"MRC Integrative Epidemiology Unit at University of Bristol, Bristol BS8 2BN, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"McMahon","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit at University of Bristol, Bristol BS8 2BN, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ville","family":"Karhunen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Public Health, Imperial College London, 156 Norfolk Place, St Mary\u2019s Campus, London W2 1PG, UK"},{"name":"Faculty of Medicine, Northern Finland Birth Cohort Studies and Center for Life Course Health Research, University of Oulu, Aapistie 5 B, Oulu Fin-902200, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlin H","family":"Wade","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit at University of Bristol, Bristol BS8 2BN, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura J","family":"Corbin","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit at University of Bristol, Bristol BS8 2BN, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"Hughes","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit at University of Bristol, Bristol BS8 2BN, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George Davey","family":"Smith","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit at University of Bristol, Bristol BS8 2BN, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debbie A","family":"Lawlor","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit at University of Bristol, Bristol BS8 2BN, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjo-Riitta","family":"Jarvelin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Public Health, Imperial College London, 156 Norfolk Place, St Mary\u2019s Campus, London W2 1PG, UK"},{"name":"Faculty of Medicine, Northern Finland Birth Cohort Studies and Center for Life Course Health Research, University of Oulu, Aapistie 5 B, Oulu Fin-902200, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J","family":"Timpson","sequence":"additional","affiliation":[{"name":"Medical Research Council Integrative Epidemiology Unit, Avon Longitudinal Study of Parents and Children, Population Health Science, Bristol Medical School, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"2020080409503159500_ref1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.2337\/db10-1667","article-title":"Learning from glycosuria","volume":"60","author":"Ferrannini","year":"2011","journal-title":"Diabetes"},{"key":"2020080409503159500_ref2","first-page":"978","article-title":"No need for routine glycosuria\/proteinuria screen in pregnant women","volume":"54","author":"Alto","year":"2005","journal-title":"J. Fam. Pract."},{"key":"2020080409503159500_ref3","doi-asserted-by":"crossref","first-page":"e000493","DOI":"10.1136\/bmjdrc-2017-000493","article-title":"Accuracy of glycosuria, random blood glucose and risk factors as selective screening tools for gestational diabetes mellitus in comparison with universal diagnosing","volume":"6","author":"Agbozo","year":"2018","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"2020080409503159500_ref4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00125-009-1560-z","article-title":"Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: findings from a prospective pregnancy cohort","volume":"53","author":"Lawlor","year":"2010","journal-title":"Diabetologia"},{"key":"2020080409503159500_ref5","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2337\/dc11-1633","article-title":"Associations of gestational diabetes, existing diabetes, and glycosuria with offspring obesity and Cardiometabolic outcomes","volume":"35","author":"Patel","year":"2012","journal-title":"Diabetes Care"},{"key":"2020080409503159500_ref6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12887-016-0585-y","article-title":"Association of maternal diabetes\/glycosuria and pre-pregnancy body mass index with offspring indicators of non-alcoholic fatty liver disease","volume":"16","author":"Patel","year":"2016","journal-title":"BMC Pediatr."},{"key":"2020080409503159500_ref7","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1161\/CIRCULATIONAHA.113.003901","article-title":"Pregnancy complications and cardiovascular disease death","volume":"132","author":"Cirillo Piera","year":"2015","journal-title":"Circulation"},{"key":"2020080409503159500_ref8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/ng.520","article-title":"New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk","volume":"42","author":"Dupuis","year":"2010","journal-title":"Nat. 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Histol."},{"key":"2020080409503159500_ref26","doi-asserted-by":"crossref","first-page":"5793","DOI":"10.2147\/DDDT.S69926","article-title":"Empagliflozin in the treatment of type 2 diabetes: evidence to date","volume":"9","author":"Shubrook","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"2020080409503159500_ref27","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.ajhg.2018.03.021","article-title":"Estimation of genetic correlation via linkage disequilibrium score regression and genomic restricted maximum likelihood","volume":"102","author":"Ni","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"2020080409503159500_ref28","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/ije\/dys064","article-title":"Cohort profile: the \u2018children of the 90s\u2019\u2014the index offspring of the Avon longitudinal study of parents and children","volume":"42","author":"Boyd","year":"2013","journal-title":"Int. J. Epidemiol."},{"key":"2020080409503159500_ref29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/ije\/dys066","article-title":"Cohort profile: the Avon longitudinal study of parents and children: ALSPAC mothers cohort","volume":"42","author":"Fraser","year":"2013","journal-title":"Int. J. Epidemiol."},{"key":"2020080409503159500_ref30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1136\/jmedgenet-2017-104880","article-title":"GWAS on prolonged gestation (post-term birth): analysis of successive Finnish birth cohorts","volume":"55","author":"Schierding","year":"2018","journal-title":"J. Med. Genet."},{"key":"2020080409503159500_ref31","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1471-0528.1993.tb12971.x","article-title":"Labour induction policy in hospitals of different levels of specialisation","volume":"100","author":"J\u00e4rvelin","year":"1993","journal-title":"BJOG"},{"key":"2020080409503159500_ref32","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1093\/bioinformatics\/btq419","article-title":"LocusZoom: regional visualization of genome-wide association scan results","volume":"26","author":"Pruim","year":"2010","journal-title":"Bioinformatics"},{"volume-title":"R: A Language and Environment for Statistical Computing","year":"2019","author":"Development Core Team","key":"2020080409503159500_ref33"},{"issue":"Suppl 7","key":"2020080409503159500_ref34","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1186\/1753-6561-3-S7-S109","article-title":"Comparison of methods for correcting population stratification in a genome-wide association study of rheumatoid arthritis: principal-component analysis versus multidimensional scaling","volume":"3","author":"Wang","year":"2009","journal-title":"BMC Proc."},{"key":"2020080409503159500_ref35","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","article-title":"METAL: fast and efficient meta-analysis of genomewide association scans","volume":"26","author":"Willer","year":"2010","journal-title":"Bioinformatics"},{"key":"2020080409503159500_ref36","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1093\/bioinformatics\/btw613","article-title":"LD hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis","volume":"33","author":"Zheng","year":"2017","journal-title":"Bioinformatics"},{"key":"2020080409503159500_ref37","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl variant effect predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddaa054\/33449532\/ddaa054.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/29\/12\/2098\/33564037\/ddaa054.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/29\/12\/2098\/33564037\/ddaa054.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T13:50:57Z","timestamp":1596549057000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/29\/12\/2098\/5813101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,30]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,3,30]]},"published-print":{"date-parts":[[2020,7,29]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddaa054","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"type":"print","value":"0964-6906"},{"type":"electronic","value":"1460-2083"}],"subject":[],"published-other":{"date-parts":[[2020,6,15]]},"published":{"date-parts":[[2020,3,30]]}}}