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

• Published in: PLoS ONE
• Main Authors: Khan, Anokhi Ali, Rodriguez, Alina, Sebert, Sylvain, Kaakinen, Marika, Cauchi, Stephane, Froguel, Philippe, Hartikainen, Anna-Liisa, Pouta, Anneli, Jarvelin, Marjo-Riitta
• Format: Article in Journal/Newspaper
• Language: English
• Published: Mittuniversitetet, Institutionen för samhällsvetenskap 2012
• Subjects: anthropometric parameters; article; birth size; birth weight; body height; body mass; CCNL 1 gene; cohort analysis; controlled study; education; effect size; female; Finland; gene; gene frequency; genetic association; genetic variability; genotype; gestational age; head circumference; human; LERK gene; male; marriage; maternal age; maternal smoking; outcome assessment; parental schooling; parenthood; parity; pregnancy; pregnancy outcome; risk factor; sex difference; single nucleotide polymorphism; social status; social stress; Public Health; Global Health; Social Medicine and Epidemiology; Folkhälsovetenskap; global hälsa; socialmedicin och epidemiologi; Medical Genetics; Medicinsk genetik; Northern Finland
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-17067; https://doi.org/10.1371/journal.pone.0038216

Background: We 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 Findings: We 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/Significance: Social 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 ...