Common variation at 16p11.2 is associated with glycosuria in pregnancy : findings from a genome-wide association study in European women
Lee, Matthew A.; McMahon, George; Karhunen, Ville; Wade, Kaitlin H.; Corbin, Laura J.; Hughes, David A.; Smith, George Davey; Lawlor, Debbie A.; Jarvelin, Marjo-Riitta; Timpson, Nicholas J. (2020-06-15)
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, https://doi.org/10.1093/hmg/ddaa054
© 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 (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe202103107029
Tiivistelmä
Abstract
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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