Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study

Grote V; Koh WP; Lemaitre R; Raitakari O; Zhao W; Lecoeur C; Amouyel P; Sorensen TIA; Chavarro JE; Lai CQ; Mook-Kanamori DO; Khor CC; Kleber ME; Burkhardt R; Hansen T; Cooper C; Bisgaard H; Psaty BM; Yuan JM; Yu CZ; Schulz CA; YinWong T; Pahkala K; Inskip H; Gao M; Thiering E; Corella D; Zhang T; Meirhaeghe A; Rzehak P; Tjonneland A; Mohlke KL; Wang YJ; Wang CA; Mozaffarian D; Viikari J; Tiesler CMT; Balkau B; Noordam R; Voortman T; Crozier SR; Teo YY; Gruszfeld D; Fink NR; Jaddoe VV; Uitterlinden AG; van Heemst D; Franco OH; Kamatani Y; Sim XL; Pitkanen N; Vinding RK; Van Rooij FJA; Qi L; Felix JF; Gupta P; Gottrand F; Rosendaal FR; Wang TA; Ridker PM; He M; Ellervik C; Sonestedt E; van Dam R; Marouli E; Chasman DI; Koletzko B; Jameson K; Standl M; Verduci E; Dorajoo R; Shi Y; Delgado G; Escribano J; Hofman A; de Mutsert R; Mackey DA; Saw SM; Boreham CA; Cheng CY; Sabanayagam C; Bonnelykke K; Tucker KL; Akiyama M; Lehtimaki T; Tham YC; Godfrey KM; Langhendries JP; Rossing P; Kubo M; Loeffler M; Chai JF; Graff M; Zheng Y; Kahonen M; Ahluwalia TVS; Fang Z; Marz W; Lee NR; Orho-Melander M; Frazier-Wood A; Djousse L; Tai ES; Dallongeville J; Coltell O; Dennison E; Smith GD; Arnett DK; Scholz M; Niinikoski H; Hypponen E; Ordovas JM; Power C; Froguel P; North KE; Fumeron F; Huang T; Wu TC; Zhou A; Li X; Liu JJ; Overvad K; Estruch R; Sevelsted A; Moreno LA; Lim B; Deloukas P; Thiery J; Rivadeneira F; Pedersen O; Dedoussis G; Lim SH; Ericson U; Kilpelainen TO
Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study

Grote V
Koh WP
Lemaitre R
Raitakari O
Zhao W
Lecoeur C
Amouyel P
Sorensen TIA
Chavarro JE
Lai CQ
Mook-Kanamori DO
Khor CC
Kleber ME
Burkhardt R
Hansen T
Cooper C
Bisgaard H
Psaty BM
Yuan JM
Yu CZ
Schulz CA
YinWong T
Pahkala K
Inskip H
Gao M
Thiering E
Corella D
Zhang T
Meirhaeghe A
Rzehak P
Tjonneland A
Mohlke KL
Wang YJ
Wang CA
Mozaffarian D
Viikari J
Tiesler CMT
Balkau B
Noordam R
Voortman T
Crozier SR
Teo YY
Gruszfeld D
Fink NR
Jaddoe VV
Uitterlinden AG
van Heemst D
Franco OH
Kamatani Y
Sim XL
Pitkanen N
Vinding RK
Van Rooij FJA
Qi L
Felix JF
Gupta P
Gottrand F
Rosendaal FR
Wang TA
Ridker PM
He M
Ellervik C
Sonestedt E
van Dam R
Marouli E
Chasman DI
Koletzko B
Jameson K
Standl M
Verduci E
Dorajoo R
Shi Y
Delgado G
Escribano J
Hofman A
de Mutsert R
Mackey DA
Saw SM
Boreham CA
Cheng CY
Sabanayagam C
Bonnelykke K
Tucker KL
Akiyama M
Lehtimaki T
Tham YC
Godfrey KM
Langhendries JP
Rossing P
Kubo M
Loeffler M
Chai JF
Graff M
Zheng Y
Kahonen M
Ahluwalia TVS
Fang Z
Marz W
Lee NR
Orho-Melander M
Frazier-Wood A
Djousse L
Tai ES
Dallongeville J
Coltell O
Dennison E
Smith GD
Arnett DK
Scholz M
Niinikoski H
Hypponen E
Ordovas JM
Power C
Froguel P
North KE
Fumeron F
Huang T
Wu TC
Zhou A
Li X
Liu JJ
Overvad K
Estruch R
Sevelsted A
Moreno LA
Lim B
Deloukas P
Thiery J
Rivadeneira F
Pedersen O
Dedoussis G
Lim SH
Ericson U
Kilpelainen TO
Katso/Avaa
Lataukset: 

AMER MEDICAL ASSOC
doi:10.1001/jamanetworkopen.2019.10915
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042821778
Tiivistelmä
IMPORTANCE 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.OBJECTIVE To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis.DESIGN, SETTING, AND PARTICIPANTS 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 polymorphismswere used as an instrumental variable). Data from 180 056 participants from 49 studies were included.MAIN OUTCOMES AND MEASURES Type 2 diabetes and glycemic traits.RESULTS 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=4.03 x 10-5), 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.CONCLUSIONS AND RELEVANCE 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.
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