The Interplay of Variants Near LEKR and CCNL1 and Social Stress in Relation to Birth Size

Abstract

BackgroundWe previously identified via a genome wide association study variants near LEKR and CCNL1 and in the ADCY5 genes lead to lower birthweight. Here, we study the impact of these variants and social stress during pregnancy, defined as social adversity and neighborhood disparity, on infant birth size. We aimed to determine whether the addition of genetic variance magnified the observed associations.Methodology/Principal FindingsWe analyzed data from the Northern Finland Birth Cohort 1986 (n = 5369). Social adversity was defined by young maternal age (<20 years), low maternal education (<11 years), and/or single marital status. Neighborhood social disparity was assessed by discrepancy between neighborhoods relative to personal socio-economic status. These variables are indicative of social and socioeconomic stress, but also of biological risk. The adjusted multiple regression analysis showed smaller birth size in both infants of mothers who experienced social adversity (birthweight by −40.4 g, 95%CI −61.4, −19.5; birth length −0.14 cm, 95%CI −0.23, −0.05; head circumference −0.09 cm 95%CI −0.15, −0.02) and neighborhood disparity (birthweight −28.8 g, 95%CI −47.7, −10.0; birth length −0.12 cm, 95%CI −0.20, −0.05). The birthweight-lowering risk allele (SNP rs900400 near LEKR and CCNL1) magnified this association in an additive manner. However, likely due to sample size restriction, this association was not significant for the SNP rs9883204 in ADCY5. Birth size difference due to social stress was greater in the presence of birthweight-lowering alleles.Conclusions/SignificanceSocial adversity, neighborhood disparity, and genetic variants have independent associations with infant birth size in the mutually adjusted analyses. If the newborn carried a risk allele rs900400 near LEKR/CCNL1, the impact of stress on birth size was stronger. These observations give support to the hypothesis that individuals with genetic or other biological risk are more vulnerable to environmental influences. Our study indicates the need for further research to understand the mechanisms by which genes impact individual vulnerability to environmental insults.

Antenatal corticosteroid therapy (ACT) and size at birth: A population-based analysis using the Finnish Medical Birth Register

“…Because all of the background and medical variables recorded in FMBR bear clinical relevance, all were included as confounders, including, e.g., those as identified in previous work such as cohabitation with expectant father [24–25]. Thus, all available background and medical factors recorded in FMBR were used.…”

Genome‐wide association study of body mass index in subjects with alcohol dependence

“…Furthermore, a post‐GWAS analysis indicated significant interplay between variants located in this region and social stress in relation to birth size (Ali Khan et al . ). Previous studies hypothesized that weight and weight gain during pre‐natal life and infancy play a role in determining adulthood obesity (Bjerregaard et al .…”

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

“…Genetic variation near the CCNL1 gene is robustly associated with low birth weight in European individuals ( Freathy et al, 2010 ; Yaghootkar and Freathy, 2012 ; Horikoshi et al, 2013 ), specifically with growth restriction from early pregnancy onward ( Mook-Kanamori et al, 2011 ). Another study suggests that individuals who carry a risk allele for rs900400 (near CCNL1 ) are more vulnerable to stress impacting on birth weight ( Ali Khan et al, 2012 ). The relationship between birth weight and kidney disease has been debated with some groups suggesting that low birth weight is a risk factor for DKD ( Rossing et al, 1995 ) while others report that low birth weight does not increase the risk of DKD ( Fagerudd et al, 2006 ).…”