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Maternal genetic risk for type 2 diabetes tied to birth weight in offspring
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Black women with a higher genetic risk score for type 2 diabetes are more likely to have offspring with a higher birth weight, whereas a higher genetic risk score in offspring was associated with lower birth weight, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
“We found that the higher the mothers’ genetic risk score for type 2 diabetes, the heavier their babies, most likely due to enhanced fetal insulin-induced growth response,” Fasil Tekola-Ayele, PhD, an Earl Stadtman investigator with the division of intramural population health research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, told Endocrine Today. “Conversely, the higher the babies’ own genetic risk score for type 2 diabetes, the lighter their weight, which appears to be mainly attributed to shared genetic effects on birth weight and future risk for type 2 diabetes.”
Tekola-Ayele and colleagues analyzed data from 949 mother-offspring pairs of African ancestry participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Women underwent a 75-g oral glucose tolerance test between 24 and 32 weeks of gestation. Cord blood C-peptide level, maternal fasting glucose and post-OGTT 1-hour and 2-hour glucose levels were used to determine intrauterine glycemic status. Maternal and offspring DNA were genotyped at genome-wide level. Researchers selected 104 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes and calculated a weighted genetic risk score based on 91 type 2 diabetes-related SNPs separately for each mother and offspring as the sum of the dose of individual risk alleles, multiplied by the corresponding effect size reported in a genome-wide association study meta-analysis. Researchers used linear regression analyses for increasing quartiles of genetic risk score to estimate the effect of maternal and offspring genetic risk scores on offspring birth weight.
The mean gestational age at birth was 39.8 weeks, and the mean birth weight was 3,216.2 g, according to researchers. At the time of the OGTT, more than 60% of mothers had overweight or obesity. Median maternal fasting glucose level during pregnancy was 79.2 mg/dL; median 1-hour and 2-hour post-OGTT levels were 118.8 mg/dL and 106.2 mg/dL, respectively.
Maternal and offspring genetic risk scores were independently and differentially associated with offspring birth weight, according to researchers.
After adjustment for offspring genetic risk score, mean increases in birth weight across increasing quartiles of maternal genetic risk score were 83.1 g in the second quartile (95% CI, 6.5-159.6), 103.1g in the third quartile (95% CI, 26-180.2) and 92.7g in the fourth quartile (95% CI, 12.6-172.8) when compared with women in the first quartile of genetic risk score (P for trend = .041).
For offspring, genetic risk score was inversely associated with birth weight. Across increasing quartiles of genetic risk score, mean changes in birth weight were –92 g in the second quartile (95% CI, –169.2 to –14.9), –64.9 g in the third quartile (95% CI, –142.4 to 12.6) and 2 g in the fourth quartile (95% CI, –77.8 to 81.7) when compared with offspring in the lowest quartile for genetic risk score (P for trend = .032).
Cord blood C-peptide level mediated the effect of maternal genetic risk score on offspring birth weight, whereas maternal post-OGTT glucose levels showed additive effects with maternal genetic risk score on birth weight, according to researchers.
“Overall, our findings, if validated in other cohorts, highlight that determining where a pregnant woman falls in the spectrum of genetic risk for type 2 diabetes may inform prenatal interventions that can prevent abnormal fetal growth,” Tekola-Ayele said. “Future genetic studies on type 2 diabetes risk are needed in diverse populations to derive clinically relevant polygenic predictors for populations from different ancestries.” – by Regina Schaffer
For more information:
Fasil Tekola-Ayele , PhD, can be reached at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, 6710B Rockledge Dr., 6710B-3204, Bethesda, MD 20892; email: ayeleft@mail.nih.gov.
Disclosures: The authors report no relevant financial disclosures.
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