Genome-Wide Pleiotropy of Osteoporosis-Related Phenotypes: The Framingham Study

Genome-wide association studies offer an unbiased approach to identify new candidate genes for osteoporosis. We examined the Affymetrix 500K + 50K SNP GeneChip marker sets for associations with multiple osteoporosis-related traits at various skeletal sites, including bone mineral density (BMD, hip a...

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Main Authors:	Karasik, David, Hsu, Yi-Hsiang, Zhou, Yanhua, Cupples, L Adrienne, Kiel, Douglas P, Demissie, Serkalem
Format:	Online
Language:	English
Published:	Wiley Subscription Services, Inc., A Wiley Company 2010
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153998/

id	pubmed-3153998
recordtype	oai_dc
spelling	pubmed-31539982011-08-19 Genome-Wide Pleiotropy of Osteoporosis-Related Phenotypes: The Framingham Study Karasik, David Hsu, Yi-Hsiang Zhou, Yanhua Cupples, L Adrienne Kiel, Douglas P Demissie, Serkalem Original Article Genome-wide association studies offer an unbiased approach to identify new candidate genes for osteoporosis. We examined the Affymetrix 500K + 50K SNP GeneChip marker sets for associations with multiple osteoporosis-related traits at various skeletal sites, including bone mineral density (BMD, hip and spine), heel ultrasound, and hip geometric indices in the Framingham Osteoporosis Study. We evaluated 433,510 single-nucleotide polymorphisms (SNPs) in 2073 women (mean age 65 years), members of two-generational families. Variance components analysis was performed to estimate phenotypic, genetic, and environmental correlations (ρP, ρG, and ρE) among bone traits. Linear mixed-effects models were used to test associations between SNPs and multivariable-adjusted trait values. We evaluated the proportion of SNPs associated with pairs of the traits at a nominal significance threshold α = 0.01. We found substantial correlation between the proportion of associated SNPs and the ρP and ρG (r = 0.91 and 0.84, respectively) but much lower with ρE (r = 0.38). Thus, for example, hip and spine BMD had 6.8% associated SNPs in common, corresponding to ρP = 0.55 and ρG = 0.66 between them. Fewer SNPs were associated with both BMD and any of the hip geometric traits (eg, femoral neck and shaft width, section moduli, neck shaft angle, and neck length); ρG between BMD and geometric traits ranged from −0.24 to +0.40. In conclusion, we examined relationships between osteoporosis-related traits based on genome-wide associations. Most of the similarity between the quantitative bone phenotypes may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in defining the best phenotypes to be used in genetic studies of osteoporosis. © 2010 American Society for Bone and Mineral Research. Wiley Subscription Services, Inc., A Wiley Company 2010-07 2010-01-29 /pmc/articles/PMC3153998/ /pubmed/20200953 http://dx.doi.org/10.1002/jbmr.38 Text en Copyright © 2010 American Society for Bone and Mineral Research http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Karasik, David Hsu, Yi-Hsiang Zhou, Yanhua Cupples, L Adrienne Kiel, Douglas P Demissie, Serkalem
spellingShingle	Karasik, David Hsu, Yi-Hsiang Zhou, Yanhua Cupples, L Adrienne Kiel, Douglas P Demissie, Serkalem Genome-Wide Pleiotropy of Osteoporosis-Related Phenotypes: The Framingham Study
author_facet	Karasik, David Hsu, Yi-Hsiang Zhou, Yanhua Cupples, L Adrienne Kiel, Douglas P Demissie, Serkalem
author_sort	Karasik, David
title	Genome-Wide Pleiotropy of Osteoporosis-Related Phenotypes: The Framingham Study
title_short	Genome-Wide Pleiotropy of Osteoporosis-Related Phenotypes: The Framingham Study
title_full	Genome-Wide Pleiotropy of Osteoporosis-Related Phenotypes: The Framingham Study
title_fullStr	Genome-Wide Pleiotropy of Osteoporosis-Related Phenotypes: The Framingham Study
title_full_unstemmed	Genome-Wide Pleiotropy of Osteoporosis-Related Phenotypes: The Framingham Study
title_sort	genome-wide pleiotropy of osteoporosis-related phenotypes: the framingham study
description	Genome-wide association studies offer an unbiased approach to identify new candidate genes for osteoporosis. We examined the Affymetrix 500K + 50K SNP GeneChip marker sets for associations with multiple osteoporosis-related traits at various skeletal sites, including bone mineral density (BMD, hip and spine), heel ultrasound, and hip geometric indices in the Framingham Osteoporosis Study. We evaluated 433,510 single-nucleotide polymorphisms (SNPs) in 2073 women (mean age 65 years), members of two-generational families. Variance components analysis was performed to estimate phenotypic, genetic, and environmental correlations (ρP, ρG, and ρE) among bone traits. Linear mixed-effects models were used to test associations between SNPs and multivariable-adjusted trait values. We evaluated the proportion of SNPs associated with pairs of the traits at a nominal significance threshold α = 0.01. We found substantial correlation between the proportion of associated SNPs and the ρP and ρG (r = 0.91 and 0.84, respectively) but much lower with ρE (r = 0.38). Thus, for example, hip and spine BMD had 6.8% associated SNPs in common, corresponding to ρP = 0.55 and ρG = 0.66 between them. Fewer SNPs were associated with both BMD and any of the hip geometric traits (eg, femoral neck and shaft width, section moduli, neck shaft angle, and neck length); ρG between BMD and geometric traits ranged from −0.24 to +0.40. In conclusion, we examined relationships between osteoporosis-related traits based on genome-wide associations. Most of the similarity between the quantitative bone phenotypes may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in defining the best phenotypes to be used in genetic studies of osteoporosis. © 2010 American Society for Bone and Mineral Research.
publisher	Wiley Subscription Services, Inc., A Wiley Company
publishDate	2010
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153998/
_version_	1611470334750359552

Genome-Wide Pleiotropy of Osteoporosis-Related Phenotypes: The Framingham Study

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