Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women
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...
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ftpubmed:oai:pubmedcentral.nih.gov:7390941 2023-05-15T17:42:48+02:00 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 2020-07-29 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390941/ http://www.ncbi.nlm.nih.gov/pubmed/32227112 https://doi.org/10.1093/hmg/ddaa054 en eng Oxford University Press http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390941/ http://www.ncbi.nlm.nih.gov/pubmed/32227112 http://dx.doi.org/10.1093/hmg/ddaa054 © The Author(s) 2020. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ 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. CC-BY Hum Mol Genet Association Studies Article Text 2020 ftpubmed https://doi.org/10.1093/hmg/ddaa054 2020-08-09T00:32:31Z 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 (R(g) = 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. Text Northern Finland PubMed Central (PMC) Human Molecular Genetics 29 12 2098 2106 |
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Association Studies Article |
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Association Studies Article 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 Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women |
topic_facet |
Association Studies Article |
description |
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 (R(g) = 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. |
format |
Text |
author |
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 |
author_facet |
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 |
author_sort |
Lee, Matthew A |
title |
Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women |
title_short |
Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women |
title_full |
Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women |
title_fullStr |
Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women |
title_full_unstemmed |
Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women |
title_sort |
common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in european women |
publisher |
Oxford University Press |
publishDate |
2020 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390941/ http://www.ncbi.nlm.nih.gov/pubmed/32227112 https://doi.org/10.1093/hmg/ddaa054 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
Hum Mol Genet |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390941/ http://www.ncbi.nlm.nih.gov/pubmed/32227112 http://dx.doi.org/10.1093/hmg/ddaa054 |
op_rights |
© The Author(s) 2020. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ 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. |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1093/hmg/ddaa054 |
container_title |
Human Molecular Genetics |
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29 |
container_issue |
12 |
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2098 |
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2106 |
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1766144713358835712 |