Associations of genome-wide and regional autozygosity with 96 complex traits in old order Amish

Background: Autozygosity, the proportion of the genome that is homozygous by descent, has been associated with variation in multiple health-related traits impacting evolutionary fitness. Autozygosity (FROH) is typically measured from runs of homozygosity (ROHs) that arise when identical-by-descent (...

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Veröffentlicht in:BMC genomics Jg. 24; H. 1; S. 134 - 9
Hauptverfasser: Lynch, Megan T., Maloney, Kristin A., Xu, Huichun, Perry, James A., Center, Regeneron Genetics, Shuldiner, Alan R., Mitchell, Braxton D.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 20.03.2023
BioMed Central Ltd
BMC
Schlagworte:
Amish
Amish - genetics
Animal Genetics and Genomics
Autozygosity
Biomedical and Life Sciences
Founder population genetics
Genetic aspects
Genetic research
Genome
Health aspects
Homozygosity
Homozygote
Humans
Inbreeding
Life Sciences
Microarrays
Microbial Genetics and Genomics
Multifactorial Inheritance
Plant Genetics and Genomics
Polymorphism, Single Nucleotide
Population genetics
Proteomics
Runs of Homozygosity
United States
Autozygosity
Runs of Homozygosity
Amish
Founder population genetics
ISSN:1471-2164, 1471-2164
Online-Zugang:Volltext
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Zusammenfassung:Background: Autozygosity, the proportion of the genome that is homozygous by descent, has been associated with variation in multiple health-related traits impacting evolutionary fitness. Autozygosity (FROH) is typically measured from runs of homozygosity (ROHs) that arise when identical-by-descent (IBD) haplotypes are inherited from each parent. Population isolates with a small set of common founders have elevated autozygosity relative to outbred populations. Methods: In this study, we examined whether degree of autozygosity was associated with variation in 96 cardiometabolic traits among 7221 Old Order Amish individuals residing in Lancaster County, PA. We estimated the average length of an ROH segment to be 6350 KB, with each individual having on average 17.2 segments 1.5 KB or larger. Measurements of genome-wide and regional FROH were used as the primary predictors of trait variation in association analysis. Results: In genome-wide FROH analysis, we did not identify any associations that withstood Bonferroni-correction (p = 0.0005). However, on regional FROH analysis, we identified associations exceeding genome-wide thresholds for two traits: serum bilirubin levels, which were significantly associated with a region on chromosome 2 localized to a region surrounding UGT1A10 (p = 1 × 10− 43), and HbA1c levels, which were significantly associated with a region on chromosome 8 localized near CHRNB3 (p = 8 × 10− 10). Conclusions: These analyses highlight the potential value of autozygosity mapping in founder populations.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1471-2164
1471-2164
DOI:10.1186/s12864-023-09208-5