| Literature DB >> 35220425 |
Natalia Pervjakova1, Gunn-Helen Moen2,3,4,5, Maria-Carolina Borges5,6, Teresa Ferreira7, James P Cook8, Catherine Allard9, Robin N Beaumont10, Mickaël Canouil11,12, Gad Hatem13, Anni Heiskala14, Anni Joensuu15,16, Ville Karhunen14,17, Soo Heon Kwak18, Frederick T J Lin19, Jun Liu20,21, Sheryl Rifas-Shiman22, Claudia H Tam23, Wing Hung Tam24, Gudmar Thorleifsson25, Toby Andrew11,12,26, Juha Auvinen14, Bishwajit Bhowmik27, Amélie Bonnefond11,12,26, Fabien Delahaye11,12, Ayse Demirkan20,28, Philippe Froguel11,12,26, Kadri Haller-Kikkatalo29, Hildur Hardardottir30,31, Sandra Hummel32,33, Akhtar Hussain27,34, Eero Kajantie35,36,37, Elina Keikkala35,36, Amna Khamis11,12,26, Jari Lahti38, Tove Lekva39, Sanna Mustaniemi35,36, Christine Sommer40, Aili Tagoma29, Evangelia Tzala17, Raivo Uibo29, Marja Vääräsmäki36,35, Pia M Villa41,42, Kåre I Birkeland2,43, Luigi Bouchard44,45, Cornelia M Duijn20,21, Sarah Finer46, Leif Groop13,47, Esa Hämäläinen48, Geoffrey M Hayes19,49,50, Graham A Hitman46, Hak C Jang51,52, Marjo-Riitta Järvelin14,17, Anne Karen Jenum53, Hannele Laivuori47,54,55, Ronald C Ma23,56,57, Olle Melander13, Emily Oken22, Kyong Soo Park18,52,58, Patrice Perron9,59, Rashmi B Prasad13, Elisabeth Qvigstad40,2, Sylvain Sebert14, Kari Stefansson25,30, Valgerdur Steinthorsdottir25, Tiinamaija Tuomi47,13,60,61, Marie-France Hivert22,59,62, Paul W Franks63,64, Mark I McCarthy65,66, Cecilia M Lindgren7,66,67, Rachel M Freathy10, Deborah A Lawlor5,6,68, Andrew P Morris69, Reedik Mägi1.
Abstract
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 Consortium assembled genome-wide association studies 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 < 5 × 10-8) with GDM, mapping to/near MTNR1B (P = 4.3 × 10-54), TCF7L2 (P = 4.0 × 10-16), CDKAL1 (P = 1.6 × 10-14), CDKN2A-CDKN2B (P = 4.1 × 10-9) and HKDC1 (P = 2.9 × 10-8). 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 randomization 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.Entities:
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Year: 2022 PMID： 35220425 PMCID： PMC9523562 DOI： 10.1093/hmg/ddac050
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 5.121