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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #368511
Title: Association of birth weight with type 2 diabetes and glycemic traits: A Mendelian randomization study

Author
item HUANG, TAO - Peking University
item WANG, TIANGE - Shanghai Jiaotong University
item ZHENG, YAN - Harvard School Of Public Health
item ELLERVIK, CHRISTINA - University Of Copenhagen
item LI, XIANG - Tulane University
item GAO, MENG - Peking University
item FANG, ZHE - Peking University
item CHAI, JIN - National University Of Singapore
item AHLUWALIA, TARUN - University Of Copenhagen
item WANG, YUJIE - University Of North Carolina
item VOORTMAN, TRUDY - Erasmus Medical Center
item NOORDAM, RAYMOND - Leiden University Medical Center
item FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item SCHOLZ, MARKUS - University Of Leipzig
item SONESTEDT, EMILY - Lund University
item AKIYAMA, MASATO - Riken Institute
item DORAJOO, RAJKUMAR - Genome Institute Of Singapore
item ZHOU, ANG - University Of South Australia
item KILPELAINEN, TUOMAS - University Of Copenhagen
item KLEBER, MARCUS - Heidelberg University
item GROZIER, SARAH - University Of Southampton
item GODFREY, KEITH - University Of Southampton
item LEMAITRE, ROZENN - University Of Washington
item FELIX, JANINE - Erasmus Medical Center
item LEHTIMAKI, TERHO - University Of Tampere
item WANG, CAROL - University Of Western Australia
item Lai, Chao Qiang
item VAN ROOIJ, FRANK - Erasmus Medical Center
item UTTERLINDEN, ANDRE - Erasmus Medical Center
item HOFMAN, ALBERT - Erasmus Medical Center
item VAN HEEMST, DIANA - Leiden University Medical Center
item ROSENDAAL, FRITS - Leiden University Medical Center
item DE MUTSERT, RENEE - Leiden University Medical Center
item BURKHARDT, RALPH - University Of Leipzig
item SCHULZ, CHRISTINA - Lund University
item ERICSON, ULRIKA - Lund University
item KAMATANI, YOICHIRO - Riken Institute
item YUAN, JIAN - University Of Pittsburgh
item POWER, CHRIS - Great Ormond Street Hospital For Children
item HANSEN, TORBEN - University Of Copenhagen
item SORENSEN, THORKILD - University Of Copenhagen
item TJONNELAND, ANNE - Danish Cancer Society Research Center
item OVERVAD, KIM - Aarhus University
item DELGADO, GRACIELA - Heidelberg University
item COOPER, CYRUS - University Of Southampton
item DJOUSSE, LUC - Brigham & Women'S Hospital
item RIVADENEIRA, FERNANDO - Erasmus Medical Center
item JAMESON, KAREN - University Of Southampton
item LIU, JIANJUN - National University Of Singapore
item KAHONEN, MIKA - Tampere University Hospital
item VIIKARI, JORMA - University Of Turku
item ESCRIBANO, JOAQUIN - University Rovira I Virgili
item VERDUCI, ELVIRA - University Of Milan
item DEDOUSSIS, GEORGE - Harokopio University Of Athens
item YU, CAIZHENG - Huazhong University Of Science And Technology
item FROGUEL, PHILLIPPE - Université Lille Nord De France
item BALKAU, BEVERLEY - University Of Paris
item FINK, NADIA - University Of Copenhagen
item VINDING, REBECCA - University Of Copenhagen
item SEVELSTED, ASTRID - University Of Copenhagen
item BISGAARD, HANS - University Of Copenhagen
item COLTELL, OSCAR - Instituto De Salud Carlos Iii
item DALLONGEVILLE, JEAN - Universite De Lille
item GOTTRAND, FREDERIC - Universite De Lille
item PAHKALA, KATJA - Great Ormond Street Hospital For Children
item NIINIKOSKI, HARRI - University Of Turku
item HYPPONEN, ELINA - Great Ormond Street Hospital For Children
item PEDERSON, OLUF - University Of Copenhagen
item MARZ, WINFRIED - Heidelberg University
item INSKIP, HAZEL - University Of Southampton
item JADDOE, VINCENT - Erasmus Medical Center
item DENNISON, ELAINE - University Of Southampton
item WONG, TIEN - National University Of Singapore
item TAI, E - National University Of Singapore
item MOHLKE, KAREN - University Of North Carolina
item MACKEY, DAVID - University Of Western Australia
item DELOUKAS, PANAGIOTIS - Queen Mary University Of London
item TUCKER, KATHERINE - University Of Massachusetts
item FUMERON, FREDERIC - Cordelier Research Center
item BONNELYKKE, KLAUS - University Of Copenhagen
item ESTRUCH, RAMON - Instituto De Salud Carlos Iii
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ARNETT, DONNA - University Of Kentucky
item MEIRHAEGHE, ALINE - Universite De Lille
item AMOUYEL, PHILIPPE - Universite De Lille
item MOZAFFARIAN, DARIUSH - Tufts University
item PSATY, BRUCE - University Of Washington
item FRANCO, OSCAR - Erasmus Medical Center
item WU, TANGCHUN - Huazhong University Of Science And Technology
item NORTH, KARI - University Of North Carolina
item DAVEY SMITH, GEORGE - University Of Bristol
item CHAVARRO, JORGE - Harvard School Of Public Health
item CHASMAN, DANIEL - Brigham & Women'S Hospital
item QI, LU - Harvard School Of Public Health

Submitted to: JAMA Network Open
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/31/2019
Publication Date: 9/20/2019
Citation: BIRTH-GENE (BIG) Study Working Group. 2019. Association of birth weight with type 2 diabetes and glycemic traits: A Mendelian randomization study. JAMA Network Open. 2(9):e1910915. https://doi.org/10.1001/jamanetworkopen.2019.10915.
DOI: https://doi.org/10.1001/jamanetworkopen.2019.10915

Interpretive Summary: Scientists now think that some of the factors that contribute to obesity and its associated health problems such as type 2 diabetes start very early in life, even if people do not develop obesity until late in life. However, we know very little about what those early life risk factors might be. In particular, there is a lack of data on factors in infancy that associate with disease risk in adulthood. This deficiency arises, in part, because it is very difficult to collect data on people from infancy all the way through to adulthood. A new analysis technique called Mendelian randomization can allow scientists to infer links between risk factors and outcomes using cross-sectional data which are easier to collect. Mendelian randomization analyzes associations between genetic risk for a trait and outcomes. In this case, we analyzed the association between genetic risk for a low birth weight and the ability to control blood sugar in adulthood. The study found that the genetic predisposition to lower birth weight was associated with an increased risk of type 2 diabetes and increased fasting glucose in adulthood. This study is important because it uses some of the most cutting edge genetic data and genetic analysis techniques to add to our understanding of whether a low birth weight increases diabetes risk in adulthood. As we know very little about the links between infancy and risk of type 2 diabetes in adulthood, this study provides important data that might be used in future risk stratification efforts which better identifies who is at risk of type 2 diabetes and thus focusses diabetes prevention efforts where they are most needed.

Technical Abstract: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. The objective of this study was to test the association of birth weight with T2D and glycemic traits using a Mendelian randomization analysis. This Mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a Mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180,056 participants from 49 studies were included. This Mendelian randomization analysis included 49 studies with 41,155 patients with T2D and 80,008 control participants from study-level data and 34,840 patients with T2D and 114,981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P=4.03X10**-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P=.04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P=04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (Beta=0.189; SE=0.060; P=.002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.