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.
Highlights
Being born small is associated with increased risk of perinatal morbidity and hospitalization [1,2], poorer developmental and cognitive outcomes in childhood [3,4], as well as cardiovascular disease, non-insulin dependent diabetes and intermediate risk factors for chronic diseases in adulthood [5,6,7,8,9,10,11]
We recently identified in a large-scale genome wide association study (GWAS) that variants near LEKR and CCNL1 and in the
Single-parenthood was the component of the social adversity composite that showed the strongest association with birth size in comparison to infants from twoparent families in a mutually adjusted analysis
Summary
Being born small is associated with increased risk of perinatal morbidity and hospitalization [1,2], poorer developmental and cognitive outcomes in childhood [3,4], as well as cardiovascular disease, non-insulin dependent diabetes and intermediate risk factors for chronic diseases in adulthood [5,6,7,8,9,10,11]. Various environmental factors including social stress characterized by low social class, social adversity, or social disparity, have been linked to small birth size, though results are inconsistent [13,14,15,16,17]. This inconsistency may be due to methodological differences across studies concerning measurement of social factors, insufficient statistical power, and inclusion of covariates. We previously identified via a genome wide association study variants near LEKR and CCNL1 and in the ADCY5 genes lead to lower birthweight. We aimed to determine whether the addition of genetic variance magnified the observed associations
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