Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth

Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such ‘missing heritability’ may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10−8; empirical PG × E=1.2 × 10−8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10−9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB.HSN268200782096CHHSN268201200008I20-FY02-56, #21-FY07-605R21ES011666R21HD0664712R01HD041702101-2314-B-400-009-MY2103-2314-B-400-004-MY32016YFC02065079164320121477087NICHD R24HD04285

Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10 -8) and rs9275596 (P=6.8 × 10 -10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (

Racial and ethnic differences in physical activity among mothers of young children: 2011–2018 NHANES

Abstract Background American women tend to reduce physical activity (PA) during the transition to motherhood. Their main barrier to participation in PA is lack of time due to new/increased parenting and housework responsibilities. Because there are known racial/ethnic variations in time spent on housework among American women, their PA changes during the transition to motherhood might also differ by racial/ ethnic background. This study aimed to compare PA between American mothers of young child(ren) under age 5 years (YC) and American women without children by their racial/ethnic background. Methods Secondary data analyses were conducted using 2011–2018 US National Health and Nutrition Survey data. The study sample included 4,892 women aged 20–45 years (Asian n = 760; Black n = 1,162; Hispanic n = 1,324; White n = 1,646). Participants completed a Physical Activity Questionnaire that asked about participation in transportation and leisure-time moderate- and vigorous-intensity PA (MVPA; minutes/week). Multivariable regression analyses were conducted to compare MVPA among women living without children and with YC (no older children) in each of the racial/ethnic groups. Results Overall, the prevalence of physical inactivity, defined as zero minutes of MVPA in a typical week, was 43% (95% CI = 38–49%) vs. 32% (95% CI = 29–35%) among women living with YC vs. without children. The adjusted odds of physical inactivity for women living with YC, compared to women living without children, was significantly higher among Asian (OR = 2.08 [95% CI = 1.37–3.17]) and White women (OR = 1.63 [95% CI = 1.11–2.38]), while it was statistically insignificant among Hispanic and Black women. Among women who reported participating in MVPA, Asian women living with YC had 35 fewer minutes/week of MVPA than their counterparts living without children (p = 0.06), while other racial and ethnic groups showed no significant differences. Conclusions American mothers of YC were less likely to engage in transportation or leisure-time MVPA, compared to those living without children. This association was particularly strong among Asian women. The study results suggest that a PA reduction in the transition to motherhood may be particularly large among Asian American women, calling for targeted efforts for PA promotion among Asian American mothers of YC; e.g., culturally-tailored community-based physical activity programs for Asian American mothers

Gestational Diabetes Mellitus, Postpartum Lipidomic Signatures, and Subsequent Risk of Type 2 Diabetes: A Lipidome-Wide Association Study

OBJECTIVE To identify a postpartum lipidomic signature associated with gestational diabetes (GDM) and investigate the role of the identified lipids in the progression to type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This was a prospective cohort study of 1409 women who were enrolled at 24-72 hours after delivery of a singleton baby and followed prospectively at the Boston Medical Center, Boston, MA. Lipidome was profiled by liquid chromatography–tandem mass spectrometry platform. Diagnoses of GDM and incident T2D were extracted from medical records and verified using plasma glucose levels.  RESULTS Mean (SD) age of study women at baseline was 28.5±6.6 years. 219 (16.4%) women developed incident diabetes over a median (interquartile range) follow-up of 11.8 (8.2-14.8) years. We identified 33 postpartum lipid species associated with GDM, including 16 inverse associations (primarily cholesterol esters and phosphatidylcholine plasmalogens), and 17 positive associations (primarily diacyglycerols and triacyglycerols). Of these, 4 were associated with risk of incident T2D and mediated about 12% of the progression from GDM to T2D. The identified lipid species modestly improved the predictive performance for incident T2D above classical risk factors when the entire follow-up period was considered.  CONCLUSIONS GDM was associated with a wide range of lipid metabolic alterations at early postpartum, among which some lipid species were also associated with incident T2D and mediated the progression from GDM to T2D. The improvements attained by including lipid species in the prediction of T2D provides new insights regarding the early detection and prevention of progression to T2D.</p

Maternal Biomarkers of Acetaminophen Use and Offspring Attention Deficit Hyperactivity Disorder

Previous studies have suggested a positive association between self-reported maternal acetaminophen use during pregnancy and risk of attention deficit hyperactivity disorder (ADHD) in offspring. We sought to examine the prospective association between maternal plasma biomarkers of acetaminophen intake and ADHD diagnosis in the offspring. This report analyzed 1180 children enrolled at birth and followed prospectively as part of the Boston Birth Cohort, including 188 with ADHD diagnosis based on electronic medical record review. Maternal biomarkers of acetaminophen intake were measured in plasma samples obtained within 1&ndash;3 days postpartum. Odds ratios for having ADHD diagnosis or other developmental disorders were estimated using multinomial logistic regression models, adjusting for pertinent covariables. Compared to neurotypical children, we observed significant positive dose-responsive associations with ADHD diagnosis for each maternal acetaminophen biomarker. These dose&ndash;responsive associations persisted after adjusting for indication of acetaminophen use and other pertinent covariates; and were specific to ADHD, rather than other neurodevelopmental disorders. In the stratified analyses, differential point estimates of the associations were observed across some strata of covariates. However, these differences were not statistically significant. Maternal acetaminophen biomarkers were specifically associated with increased risk of ADHD diagnosis in offspring. Additional clinical and mechanistic investigations are warranted

A Prospective Birth Cohort Study on Maternal Cholesterol Levels and Offspring Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences

Growing evidence suggests that maternal cholesterol levels are important in the offspring’s brain growth and development. Previous studies on cholesterols and brain functions were mostly in adults. We sought to examine the prospective association between maternal cholesterol levels and the risk of attention deficit hyperactivity disorder (ADHD) in the offspring. We analyzed data from the Boston Birth Cohort, enrolled at birth and followed from birth up to age 15 years. The final analyses included 1479 mother-infant pairs: 303 children with ADHD, and 1176 neurotypical children without clinician-diagnosed neurodevelopmental disorders. The median age of the first diagnosis of ADHD was seven years. The multiple logistic regression results showed that a low maternal high-density lipoprotein level (≤60 mg/dL) was associated with an increased risk of ADHD, compared to a higher maternal high-density lipoprotein level, after adjusting for pertinent covariables. A “J” shaped relationship was observed between triglycerides and ADHD risk. The associations with ADHD for maternal high-density lipoprotein and triglycerides were more pronounced among boys. The findings based on this predominantly urban low-income minority birth cohort raise a new mechanistic perspective for understanding the origins of ADHD and the gender differences and future targets in the prevention of ADHD

Genome-wide DNA methylation associations with spontaneous preterm birth in US blacks: findings in maternal and cord blood samples

<p>Preterm birth (PTB) affects one in six Black babies in the United States. Epigenetics is believed to play a role in PTB; however, only a limited number of epigenetic studies of PTB have been reported, most of which have focused on cord blood DNA methylation (DNAm) and/or were conducted in white populations. Here we conducted, by far, the largest epigenome-wide DNAm analysis in 300 Black women who delivered early spontaneous preterm (sPTB, n = 150) or full-term babies (n = 150) and replicated the findings in an independent set of Black mother-newborn pairs from the Boston Birth Cohort. DNAm in maternal blood and/or cord blood was measured using the Illumina HumanMethylation450 BeadChip. We identified 45 DNAm loci in maternal blood associated with early sPTB, with a false discovery rate (FDR) <5%. Replication analyses confirmed sPTB associations for cg03915055 and cg06804705, located in the promoter regions of the <i>CYTIP</i> and <i>LINC00114</i> genes, respectively. Both loci had comparable associations with early sPTB and early medically-indicated PTB, but attenuated associations with late sPTB. These associations could not be explained by cell composition, gestational complications, and/or nearby maternal genetic variants. Analyses in the newborns of the 110 Black women showed that cord blood methylation levels at both loci had no associations with PTB. The findings from this study underscore the role of maternal DNAm in PTB risk, and provide a set of maternal loci that may serve as biomarkers for PTB. Longitudinal studies are needed to clarify temporal relationships between maternal DNAm and PTB risk.</p