University of Oulu

Matthew A Lee, George McMahon, Ville Karhunen, Kaitlin H Wade, Laura J Corbin, David A Hughes, George Davey Smith, Debbie A Lawlor, Marjo-Riitta Jarvelin, Nicholas J Timpson, Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women, Human Molecular Genetics, Volume 29, Issue 12, 15 June 2020, Pages 2098–2106,

Common variation at 16p11.2 is associated with glycosuria in pregnancy : findings from a genome-wide association study in European women

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Author: Lee, Matthew A.1,2; McMahon, George1,2; Karhunen, Ville3,4;
Organizations: 1MRC Integrative Epidemiology Unit at University of Bristol, Bristol BS8 2BN, UK
2Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK
3Faculty of Medicine, School of Public Health, Imperial College London, 156 Norfolk Place, St Mary’s Campus, London W2 1PG, UK
4Faculty of Medicine,Northern Finland Birth Cohort Studies and Center for Life Course Health Research, University of Oulu, Aapistie 5 B, Oulu Fin-902200, Finland
5Medical 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
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
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Language: English
Published: Oxford University Press, 2020
Publish Date: 2021-03-10


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 = 1249/5140). We identified two loci, one of which (lead SNP = rs13337037; chromosome 16; odds ratio of glycosuria per effect allele: 1.42; 95% CI: 1.30, 1.56; P = 1.97 × 10⁻¹³) 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 = 0.64; SE = 0.22; P = 0.0042), 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.

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Series: Human molecular genetics
ISSN: 0964-6906
ISSN-E: 1460-2083
ISSN-L: 0964-6906
Volume: 29
Issue: 12
Pages: 2098 - 2106
DOI: 10.1093/hmg/ddaa054
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3123 Gynaecology and paediatrics
Funding: This work was supported by the Wellcome Trust through a Wellcome Trust Investigator award to NJT (202802/Z/16/Z); and through the core programme support for The Avon Longitudinal Study for Parents and Children (102215). The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and M.A.L and N.J.T. will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (; genetic data for this research were specifically funded by The Wellcome Trust (WT08806). NFBC1986 is funded by EU QLG1-CT-2000-01643 (EUROBLCS) grant no. E51560, NorFA grant no. 731, 20056, 30167 and USA/NIHH 2000 G DF682 grant no. 50945. G.D.S., N.J.T., D.A.L., K.H.W., L.J.C., D.A.H., G.M. and M.A.L. work in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (grant numbers for 2013-2018: MC_UU_12013/1-6; 2018-2023: MC_UU_00011/1-7) and the University of Bristol. M.A.L. is funded by a GW4 studentship (grant number: MR/R502340/1). N.J.T. is a Wellcome Trust Investigator (202802/Z/16/Z) and the PI of the ALSPAC (MRC & WT 102215/2/13/2), is supported by the University of Bristol NIHR Biomedical Research Centre (S- BRC-1215-20011), the MRC Integrative Epidemiology Unit (MC_UU_12013/3) and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). K.H.W, L.J.C and D.A.H are supported by N.J.T.’s Wellcome Trust Investigator award (202802/Z/16/Z).
Copyright information: © The Author(s) 2020. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.