Genome-wide association study of parity in Bangladeshi women.

Briseis Aschebrook-Kilfoy,Muhammad G Kibriya,Farzana Jasmine,Brandon L Pierce,Shantanu Roy,Maria Argos,Faruque Parvez,Habibul Ahsan,Alauddin Ahmed,Tariqul Islam,Lin Tong,Yibin Wang

doi:10.1371/journal.pone.0118488

Briseis Aschebrook-Kilfoy, Muhammad G Kibriya + Show 10 more

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https://doi.org/10.1371/journal.pone.0118488

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Abstract

Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component. To better understand inter-individual variability in fertility, we performed one of the first genome-wide association studies (GWAS) of common fertility phenotypes, lifetime number of pregnancies and number of children in a developing country population. The fertility phenotype data and DNA samples were obtained at baseline recruitment from individuals participating in a large prospective cohort study in Bangladesh. GWAS analyses of fertility phenotypes were conducted among 1,686 married women. One SNP on chromosome 4 was non-significantly associated with number of children at P <10-7 and number of pregnancies at P <10-6. This SNP is located in a region without a gene within 1 Mb. One SNP on chromosome 6 was non-significantly associated with extreme number of children at P <10-6. The closest gene to this SNP is HDGFL1, a hepatoma-derived growth factor. When we excluded hormonal contraceptive users, a SNP on chromosome 5 was non-significantly associated at P <10-5 for number of children and number of pregnancies. This SNP is located near C5orf64, an open reading frame, and ZSWIM6, a zinc ion binding gene. We also estimated the heritability of these phenotypes from our genotype data using GCTA (Genome-wide Complex Trait Analysis) for number of children (hg 2 = 0.149, SE = 0.24, p-value = 0.265) and number of pregnancies (hg 2 = 0.007, SE = 0.22, p-value = 0.487). Our genome-wide association study and heritability estimates of number of pregnancies and number of children in Bangladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of 3 notable SNPs in their analysis.

Highlights

Fertility i.e., the number of children that a woman will have in her life, is a relevant aspect of health, for individual family planning, clinical care, and for understanding long-term population growth
In recent years, a new physiological role in human fertility regulation has emerged for the tumor-suppressor p53 gene (P53) as the P53 Arg72Pro polymorphism has been associated with recurrent implantation failure in humans [14]
In one of the first investigations of this hypothesis using a genome-wide association studies (GWAS) approach, we identified a borderline significant association for rs100009124 and number of children when corrected for multiple comparisons in our analysis

Summary

Introduction

Fertility i.e., the number of children that a woman will have in her life, is a relevant aspect of health, for individual family planning, clinical care, and for understanding long-term population growth. Relative to the birth rate in developed countries, the fertility rate in Bangladesh has been historically high, largely because of a pattern of early childbearing and socioeconomic factors [2,3,4,5,6,7]. Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component [8,9]. The emerging evidence indicates that fertility genes represent a set of genes whose role is changing, and acquiring clinical relevance, possibly due to their interaction with the prevalent environmental context, such as changing reproductive patterns (e.g., birth control, family planning, delayed childbearing, and spacing birth order). Some polymorphic variants (alleles) have been identified in fertility genes, how these alleles affect human fertility and interact with the reproductive environment remains unclear [15,16]

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