Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes

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MARC

Fältnamn	Indikatorer	Metadata
000		07487naa a2201153 4500
001		oai:lup.lub.lu.se:6183ba7b-3d2b-4a89-8014-4f75405582aa
003		SwePub
008		220812s2022 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/6183ba7b-3d2b-4a89-8014-4f75405582aa2 URI
024	7	a https://doi.org/10.1093/hmg/ddac0502 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Pervjakova, Nataliau Tartu University Hospital4 aut
245	1 0	a Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
264		c 2022-02-26
264	1	b Oxford University Press (OUP),c 2022
520		a Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (p < 5x10-8) with GDM, mapping to/near MTNR1B (p = 4.3x10-54), TCF7L2 (p = 4.0x10-16), CDKAL1 (p = 1.6 × 10-14), CDKN2A-CDKN2B (p = 4.1x10-9) and HKDC1 (p = 2.9x10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
700	1	a Moen, Gunn-Helenu University of Oslo4 aut
700	1	a Borges, Maria-Carolinau University of Bristol4 aut
700	1	a Ferreira, Teresau University of Oxford4 aut
700	1	a Cook, James Pu University of Liverpool4 aut
700	1	a Allard, Catherineu Sherbrooke University4 aut
700	1	a Beaumont, Robin Nu University of Exeter4 aut
700	1	a Canouil, Mickaëlu Pasteur Institute of Lille4 aut
700	1	a Hatem, Gadu Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups4 aut0 (Swepub:lu)ga5503ha
700	1	a Heiskala, Anniu University of Oulu4 aut
700	1	a Joensuu, Anniu Finnish National Institute for Health and Welfare4 aut
700	1	a Karhunen, Villeu University of Oulu4 aut
700	1	a Kwak, Soo Heon4 aut
700	1	a Lin, Frederick T J4 aut
700	1	a Liu, Jun4 aut
700	1	a Rifas-Shiman, Sheryl4 aut
700	1	a Tam, Claudia H4 aut
700	1	a Tam, Wing Hung4 aut
700	1	a Thorleifsson, Gudmar4 aut
700	1	a Andrew, Toby4 aut
700	1	a Auvinen, Juha4 aut
700	1	a Bhowmik, Bishwajit4 aut
700	1	a Bonnefond, Amélie4 aut
700	1	a Delahaye, Fabien4 aut
700	1	a Demirkan, Ayse4 aut
700	1	a Froguel, Philippe4 aut
700	1	a Haller-Kikkatalo, Kadri4 aut
700	1	a Hardardottir, Hildur4 aut
700	1	a Hummel, Sandra4 aut
700	1	a Hussain, Akhtar4 aut
700	1	a Kajantie, Eero4 aut
700	1	a Keikkala, Elina4 aut
700	1	a Khamis, Amna4 aut
700	1	a Lahti, Jari4 aut
700	1	a Lekva, Tove4 aut
700	1	a Mustaniemi, Sanna4 aut
700	1	a Sommer, Christine4 aut
700	1	a Tagoma, Aili4 aut
700	1	a Tzala, Evangelia4 aut
700	1	a Uibo, Raivou University of Tartu4 aut0 (Swepub:lu)med-ruo
700	1	a Vääräsmäki, Marja4 aut
700	1	a Villa, Pia M4 aut
700	1	a Birkeland, Kåre I4 aut
700	1	a Bouchard, Luigi4 aut
700	1	a Duijn, Cornelia M4 aut
700	1	a Finer, Sarah4 aut
700	1	a Groop, Leifu Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki4 aut0 (Swepub:lu)endo-lgr
700	1	a Hämäläinen, Esa4 aut
700	1	a Hayes, Geoffrey M4 aut
700	1	a Hitman, Graham A4 aut
700	1	a Jang, Hak C4 aut
700	1	a Järvelin, Marjo-Riitta4 aut
700	1	a Jenum, Anne Karen4 aut
700	1	a Laivuori, Hannele4 aut
700	1	a Ma, Ronald C4 aut
700	1	a Melander, Olleu Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups4 aut0 (Swepub:lu)endo-ome
700	1	a Oken, Emily4 aut
700	1	a Park, Kyong Soo4 aut
700	1	a Perron, Patrice4 aut
700	1	a Prasad, Rashmi Bu Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups4 aut0 (Swepub:lu)med-rpa
700	1	a Qvigstad, Elisabeth4 aut
700	1	a Sebert, Sylvain4 aut
700	1	a Stefansson, Kari4 aut
700	1	a Steinthorsdottir, Valgerdur4 aut
700	1	a Tuomi, Tiinamaijau Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Helsinki University Central Hospital,Folkhälsan Research Center,University of Helsinki4 aut0 (Swepub:lu)ti8736tu
700	1	a Hivert, Marie-France4 aut
700	1	a Franks, Paul Wu Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Harvard University4 aut0 (Swepub:lu)med-plf
700	1	a McCarthy, Mark I4 aut
700	1	a Lindgren, Cecilia Mu Broad Institute,University of Oxford4 aut0 (Swepub:lu)endo-cli
700	1	a Freathy, Rachel M4 aut
700	1	a Lawlor, Deborah A4 aut
700	1	a Morris, Andrew P4 aut
700	1	a Mägi, Reedik4 aut
710	2	a Tartu University Hospitalb University of Oslo4 org
773	0	t Human Molecular Geneticsd : Oxford University Press (OUP)g 31:19, s. 3377-3391q 31:19<3377-3391x 0964-6906x 1460-2083
856	4	u http://dx.doi.org/10.1093/hmg/ddac050x freey FULLTEXT
856	4 8	u https://lup.lub.lu.se/record/6183ba7b-3d2b-4a89-8014-4f75405582aa
856	4 8	u https://doi.org/10.1093/hmg/ddac050

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By the author/editor: Pervjakova, Nata ...; Moen, Gunn-Helen; Borges, Maria-Ca ...; Ferreira, Teresa; Cook, James P; Allard, Catherin ...; show more...; Beaumont, Robin ...; Canouil, Mickaël; Hatem, Gad; Heiskala, Anni; Joensuu, Anni; Karhunen, Ville; Kwak, Soo Heon; Lin, Frederick T ...; Liu, Jun; Rifas-Shiman, Sh ...; Tam, Claudia H; Tam, Wing Hung; Thorleifsson, Gu ...; Andrew, Toby; Auvinen, Juha; Bhowmik, Bishwaj ...; Bonnefond, Améli ...; Delahaye, Fabien; Demirkan, Ayse; Froguel, Philipp ...; Haller-Kikkatalo ...; Hardardottir, Hi ...; Hummel, Sandra; Hussain, Akhtar; Kajantie, Eero; Keikkala, Elina; Khamis, Amna; Lahti, Jari; Lekva, Tove; Mustaniemi, Sann ...; Sommer, Christin ...; Tagoma, Aili; Tzala, Evangelia; Uibo, Raivo; Vääräsmäki, Marj ...; Villa, Pia M; Birkeland, Kåre ...; Bouchard, Luigi; Duijn, Cornelia ...; Finer, Sarah; Groop, Leif; Hämäläinen, Esa; Hayes, Geoffrey ...; Hitman, Graham A; Jang, Hak C; Järvelin, Marjo- ...; Jenum, Anne Kare ...; Laivuori, Hannel ...; Ma, Ronald C; Melander, Olle; Oken, Emily; Park, Kyong Soo; Perron, Patrice; Prasad, Rashmi B; Qvigstad, Elisab ...; Sebert, Sylvain; Stefansson, Kari; Steinthorsdottir ...; Tuomi, Tiinamaij ...; Hivert, Marie-Fr ...; Franks, Paul W; McCarthy, Mark I; Lindgren, Cecili ...; Freathy, Rachel ...; Lawlor, Deborah ...; Morris, Andrew P; Mägi, Reedik; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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