PMID- 37831898
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240214
IS  - 1464-3685 (Electronic)
IS  - 0300-5771 (Print)
IS  - 0300-5771 (Linking)
VI  - 53
IP  - 1
DP  - 2024 Feb 1
TI  - Partitioning genetic effects on birthweight at classical human leukocyte antigen 
      loci into maternal and fetal components, using structural equation modelling.
LID - 10.1093/ije/dyad142 [doi]
LID - dyad142
AB  - BACKGROUND: Single nucleotide polymorphisms in the human leukocyte antigen (HLA) 
      region in both maternal and fetal genomes have been robustly associated with 
      birthweight (BW) in previous genetic association studies. However, no study to 
      date has partitioned the association between BW and classical HLA alleles into 
      maternal and fetal components. METHODS: We used structural equation modelling 
      (SEM) to estimate the maternal and fetal effects of classical HLA alleles on BW. 
      Our SEM leverages the data structure of the UK Biobank (UKB), which includes 
       approximately 270 000 participants' own BW and/or the BW of their firstborn child. RESULTS: We 
      show via simulation that our model yields asymptotically unbiased estimates of 
      the maternal and fetal allelic effects on BW and appropriate type I error rates, 
      in contrast to simple regression models. Asymptotic power calculations show that 
      we have sufficient power to detect moderate-sized maternal or fetal allelic 
      effects of common HLA alleles on BW in the UKB. Applying our SEM to imputed 
      classical HLA alleles and own and offspring BW from the UKB replicated the 
      previously reported association at the HLA-C locus and revealed strong evidence 
      for maternal (HLA-A*03:01, B*35:01, B*39:06, P <0.001) and fetal allelic effects 
      (HLA-B*39:06, P <0.001) of non-HLA-C alleles on BW. CONCLUSIONS: Our model yields 
      asymptotically unbiased estimates, appropriate type I error rates and appreciable 
      power to estimate maternal and fetal effects on BW. These novel allelic 
      associations between BW and classical HLA alleles provide insight into the 
      immunogenetics of fetal growth in utero.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      International Epidemiological Association.
FAU - Wang, Geng
AU  - Wang G
AUID- ORCID: 0000-0003-2478-2919
AD  - Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane, QLD, 
      Australia.
AD  - Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 
      Australia.
FAU - Warrington, Nicole M
AU  - Warrington NM
AD  - Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane, QLD, 
      Australia.
AD  - Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 
      Australia.
AD  - Medical Research Council Integrative Epidemiology Unit, University of Bristol, 
      Bristol, UK.
AD  - K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and 
      Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
FAU - Evans, David M
AU  - Evans DM
AUID- ORCID: 0000-0003-0663-4621
AD  - Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane, QLD, 
      Australia.
AD  - Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 
      Australia.
AD  - Medical Research Council Integrative Epidemiology Unit, University of Bristol, 
      Bristol, UK.
LA  - eng
GR  - University of Queensland Graduate School Scholarship (Australian Government 
      Research Training Program Scholarship)/
GR  - APP2008723/National Health and Medical Research Council (Australia) Investigator 
      grant/
GR  - APP2017942/Australian National Health and Medical Research Council Investigator 
      grant/
GR  - GNT1157714/NHMRC project grants/
PT  - Journal Article
PL  - England
TA  - Int J Epidemiol
JT  - International journal of epidemiology
JID - 7802871
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Child
MH  - Humans
MH  - Birth Weight/genetics
MH  - Latent Class Analysis
MH  - *HLA Antigens/genetics
MH  - *Family
MH  - Polymorphism, Single Nucleotide
MH  - Alleles
PMC - PMC10859143
OTO - NOTNLM
OT  - Genetic association
OT  - UK Biobank
OT  - birthweight
OT  - human leukocyte antigen
OT  - structural equation modelling
COIS- None declared.
EDAT- 2023/10/13 18:43
MHDA- 2024/02/11 16:42
PMCR- 2023/10/13
CRDT- 2023/10/13 15:03
PHST- 2022/08/28 00:00 [received]
PHST- 2023/10/03 00:00 [accepted]
PHST- 2024/02/11 16:42 [medline]
PHST- 2023/10/13 18:43 [pubmed]
PHST- 2023/10/13 15:03 [entrez]
PHST- 2023/10/13 00:00 [pmc-release]
AID - 7311792 [pii]
AID - dyad142 [pii]
AID - 10.1093/ije/dyad142 [doi]
PST - ppublish
SO  - Int J Epidemiol. 2024 Feb 1;53(1):dyad142. doi: 10.1093/ije/dyad142.