Human Birth Weight and Reproductive Immunology: Testing for Interactions between Maternal and Offspring KIR and HLA-C Genes
Year: 2016
Type: article
Abstract: BACKGROUND/AIMS: Maternal and offspring cell contact at the site of placentation presents a plausible setting for maternal-fetal genotype (MFG) interactions affecting fetal growth. We test hypotheses regarding killer cell immunoglobulin-like receptor (KIR) and HLA-C MFG effects on human birth weight by extending the quantitative MFG (QMFG) test. METHODS: Until recently, association testing for MFG interactions had limited applications. To improve the ability to test for these interactions, we developed the extended QMFG test, a linear mixed-effect model that can use multi-locus genotype data from families. RESULTS: We demonstrate the extended QMFG test's statistical properties. We also show that if an offspring-only model is fit when MFG effects exist, associations can be missed or misattributed. Furthermore, imprecisely modeling the effects of both KIR and HLA-C could result in a failure to replicate if these loci's allele frequencies differ among populations. To further illustrate the extended QMFG test's advantages, we apply the extended QMFG test to a UK cohort study and the Norwegian Mother and Child Cohort (MoBa) study. CONCLUSION: We find a significant KIR-HLA-C interaction effect on birth weight. More generally, the QMFG test can detect genetic associations that may be missed by standard genome-wide association studies for quantitative traits.
Source: Human Heredity
DOI: 10.1159/000456033
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: National Science Foundation, Wellcome Trust, British Heart Foundation, National Institutes of Health, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences
Awards: The role of KIR and HLA-C in reproductive success., G1756123706, G1795185051, G1922679944, G1930730855, G1977033855, G2047650810, G2716889063, Immunogenetics of killer cell immunoglobulin-like receptors (KIR) and HLA-C in pre-eclampsia, G3193858039, How do uterine NK cells regulate placentation?, Gene-Environment Interactions in an Autism Birth Cohort, G3998038441, G4129682460, Statistical Methods for Gene Mapping, NORWAY MOTHER AND CHILD COHORT STUDY: CONTINUED SPECIMEN, Advancing the Molecular Epidemiology of Infectious Diseases through Bayesian Phylogenetics, G648019732, Genomics, EHRs, GPUs, and Next Generation Computational Statistics, G86128987, Training Grant in Genomic Analysis and Interpretation
OpenAlex ID: W2588990079