Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
Pervjakova, Natalia; Moen, Gunn Helen; Borges, Maria Carolina; Ferreira, Teresa; Cook, James P.; Allard, Catherine; Beaumont, Robin N.; Canouil, Mickaël; Hatem, Gad; Heiskala, Anni; Joensuu, Anni; Karhunen, Ville; Kwak, Soo Heon; Lin, Frederick T.J.; Liu, Jun; Rifas-Shiman, Sheryl; Tam, Claudia H.; Tam, Wing Hung; Thorleifsson, Gudmar; Andrew, Toby; Auvinen, Juha; Bhowmik, Bishwajit; Bonnefond, Amélie; Delahaye, Fabien; Demirkan, Ayse; Froguel, Philippe; Haller-Kikkatalo, Kadri; Hardardottir, Hildur; Hummel, Sandra; Hussain, Akhtar; Kajantie, Eero; Keikkala, Elina; Khamis, Amna; Lahti, Jari; Lekva, Tove; Mustaniemi, Sanna; Sommer, Christine; Tagoma, Aili; Tzala, Evangelia; Uibo, Raivo; Vääräsmäki, Marja; Villa, Pia M.; Birkeland, Kåre I.; Bouchard, Luigi; Duijn, Cornelia M.; Finer, Sarah; Groop, Leif; Hämäläinen, Esa; Hayes, Geoffrey M.; Hitman, Graham A.; Jang, Hak C.; Järvelin, Marjo Riitta; Jenum, Anne Karen; Laivuori, Hannele; Ma, Ronald C.; Melander, Olle; Oken, Emily; Park, Kyong Soo; Perron, Patrice; Prasad, Rashmi B.; Qvigstad, Elisabeth; Sebert, Sylvain; Stefansson, Kari; Steinthorsdottir, Valgerdur; Tuomi, Tiinamaija; Hivert, Marie France; Franks, Paul W.; McCarthy, Mark I.; Lindgren, Cecilia M.; Freathy, Rachel M.; Lawlor, Deborah A.; Morris, Andrew P.; Mägi, Reedik (2022-10-01)
Pervjakova, Natalia
Moen, Gunn Helen
Borges, Maria Carolina
Ferreira, Teresa
Cook, James P.
Allard, Catherine
Beaumont, Robin N.
Canouil, Mickaël
Hatem, Gad
Heiskala, Anni
Joensuu, Anni
Karhunen, Ville
Kwak, Soo Heon
Lin, Frederick T.J.
Liu, Jun
Rifas-Shiman, Sheryl
Tam, Claudia H.
Tam, Wing Hung
Thorleifsson, Gudmar
Andrew, Toby
Auvinen, Juha
Bhowmik, Bishwajit
Bonnefond, Amélie
Delahaye, Fabien
Demirkan, Ayse
Froguel, Philippe
Haller-Kikkatalo, Kadri
Hardardottir, Hildur
Hummel, Sandra
Hussain, Akhtar
Kajantie, Eero
Keikkala, Elina
Khamis, Amna
Lahti, Jari
Lekva, Tove
Mustaniemi, Sanna
Sommer, Christine
Tagoma, Aili
Tzala, Evangelia
Uibo, Raivo
Vääräsmäki, Marja
Villa, Pia M.
Birkeland, Kåre I.
Bouchard, Luigi
Duijn, Cornelia M.
Finer, Sarah
Groop, Leif
Hämäläinen, Esa
Hayes, Geoffrey M.
Hitman, Graham A.
Jang, Hak C.
Järvelin, Marjo Riitta
Jenum, Anne Karen
Laivuori, Hannele
Ma, Ronald C.
Melander, Olle
Oken, Emily
Park, Kyong Soo
Perron, Patrice
Prasad, Rashmi B.
Qvigstad, Elisabeth
Sebert, Sylvain
Stefansson, Kari
Steinthorsdottir, Valgerdur
Tuomi, Tiinamaija
Hivert, Marie France
Franks, Paul W.
McCarthy, Mark I.
Lindgren, Cecilia M.
Freathy, Rachel M.
Lawlor, Deborah A.
Morris, Andrew P.
Mägi, Reedik
01.10.2022
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202211228534
https://urn.fi/URN:NBN:fi:tuni-202211228534
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [16929]