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Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been... Full description

Journal Title: American journal of human genetics 2018-01-04, Vol.102 (1), p.88-102
Main Author: Medina-Gomez, Carolina
Other Authors: Kemp, John P , Trajanoska, Katerina , Luan, Jian’an , Chesi, Alessandra , Ahluwalia, Tarunveer S , Mook-Kanamori, Dennis O , Ham, Annelies , Hartwig, Fernando P , Evans, Daniel S , Joro, Raimo , Nedeljkovic, Ivana , Zheng, Hou-Feng , Zhu, Kun , Atalay, Mustafa , Liu, Ching-Ti , Nethander, Maria , Broer, Linda , Porleifsson, Gudmar , Mullin, Benjamin H , Handelman, Samuel K , Nalls, Mike A , Jessen, Leon E , Heppe, Denise H.M , Richards, J. Brent , Wang, Carol , Chawes, Bo , Schraut, Katharina E , Amin, Najaf , Wareham, Nick , Karasik, David , Van der Velde, Nathalie , Ikram, M. Arfan , Zemel, Babette S , Zhou, Yanhua , Carlsson, Christian J , Liu, Yongmei , McGuigan, Fiona E , Boer, Cindy G , Bønnelykke, Klaus , Ralston, Stuart H , Robbins, John A , Walsh, John P , Zillikens, M. Carola , Langenberg, Claudia , Li-Gao, Ruifang , Williams, Frances M.K , Harris, Tamara B , Akesson, Kristina , Jackson, Rebecca D , Sigurdsson, Gunnar , den Heijer, Martin , van der Eerden, Bram C.J , van de Peppel, Jeroen , Spector, Timothy D , Pennell, Craig , Horta, Bernardo L , Felix, Janine F , Zhao, Jing Hua , Wilson, Scott G , de Mutsert, Renée , Bisgaard, Hans , Styrkársdóttir, Unnur , Jaddoe, Vincent W , Orwoll, Eric , Lakka, Timo A , Scott, Robert , Grant, Struan F.A , Lorentzon, Mattias , van Duijn, Cornelia M , Wilson, James F , Stefansson, Kari , Psaty, Bruce M , Kiel, Douglas P , Ohlsson, Claes , Ntzani, Evangelia , van Wijnen, Andre J , Forgetta, Vincenzo , Ghanbari, Mohsen , Logan, John G , Williams, Graham R , Bassett, J.H. Duncan , Croucher, Peter I , Evangelou, Evangelos , Uitterlinden, Andre G , Ackert-Bicknell, Cheryl L , Tobias, Jonathan H , Evans, David M , Rivadeneira, Fernando
Format: Electronic Article Electronic Article
Language: English
Subjects:
age
BMD
Non
Quelle: Alma/SFX Local Collection
Publisher: United States: Elsevier Inc
ID: ISSN: 0002-9297
Zum Text:
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title: Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
format: Article
creator:
  • Medina-Gomez, Carolina
  • Kemp, John P
  • Trajanoska, Katerina
  • Luan, Jian’an
  • Chesi, Alessandra
  • Ahluwalia, Tarunveer S
  • Mook-Kanamori, Dennis O
  • Ham, Annelies
  • Hartwig, Fernando P
  • Evans, Daniel S
  • Joro, Raimo
  • Nedeljkovic, Ivana
  • Zheng, Hou-Feng
  • Zhu, Kun
  • Atalay, Mustafa
  • Liu, Ching-Ti
  • Nethander, Maria
  • Broer, Linda
  • Porleifsson, Gudmar
  • Mullin, Benjamin H
  • Handelman, Samuel K
  • Nalls, Mike A
  • Jessen, Leon E
  • Heppe, Denise H.M
  • Richards, J. Brent
  • Wang, Carol
  • Chawes, Bo
  • Schraut, Katharina E
  • Amin, Najaf
  • Wareham, Nick
  • Karasik, David
  • Van der Velde, Nathalie
  • Ikram, M. Arfan
  • Zemel, Babette S
  • Zhou, Yanhua
  • Carlsson, Christian J
  • Liu, Yongmei
  • McGuigan, Fiona E
  • Boer, Cindy G
  • Bønnelykke, Klaus
  • Ralston, Stuart H
  • Robbins, John A
  • Walsh, John P
  • Zillikens, M. Carola
  • Langenberg, Claudia
  • Li-Gao, Ruifang
  • Williams, Frances M.K
  • Harris, Tamara B
  • Akesson, Kristina
  • Jackson, Rebecca D
  • Sigurdsson, Gunnar
  • den Heijer, Martin
  • van der Eerden, Bram C.J
  • van de Peppel, Jeroen
  • Spector, Timothy D
  • Pennell, Craig
  • Horta, Bernardo L
  • Felix, Janine F
  • Zhao, Jing Hua
  • Wilson, Scott G
  • de Mutsert, Renée
  • Bisgaard, Hans
  • Styrkársdóttir, Unnur
  • Jaddoe, Vincent W
  • Orwoll, Eric
  • Lakka, Timo A
  • Scott, Robert
  • Grant, Struan F.A
  • Lorentzon, Mattias
  • van Duijn, Cornelia M
  • Wilson, James F
  • Stefansson, Kari
  • Psaty, Bruce M
  • Kiel, Douglas P
  • Ohlsson, Claes
  • Ntzani, Evangelia
  • van Wijnen, Andre J
  • Forgetta, Vincenzo
  • Ghanbari, Mohsen
  • Logan, John G
  • Williams, Graham R
  • Bassett, J.H. Duncan
  • Croucher, Peter I
  • Evangelou, Evangelos
  • Uitterlinden, Andre G
  • Ackert-Bicknell, Cheryl L
  • Tobias, Jonathan H
  • Evans, David M
  • Rivadeneira, Fernando
subjects:
  • 06 Biological Sciences
  • 11 Medical And Health Sciences
  • Adolescent
  • age
  • Age Factors
  • age-dependent effects
  • Analysis
  • Animals
  • Article
  • atira
  • Basic Medicine
  • BMD
  • body DXA
  • Bone Density
  • Bone Density - genetics
  • bone mineral density
  • Child
  • Child, Preschool
  • Clinical Medicine
  • CREB3L1
  • dependent effects
  • ESR1
  • fracture
  • genetic correlation
  • Genetic Loci
  • Genetic research
  • genetics
  • Genetics & Heredity
  • Genome
  • genome-wide association studies
  • Genome-Wide Association Study
  • Genomics
  • Gov't
  • GWASs
  • Heritable
  • Humans
  • Infant
  • Infant, Newborn
  • Journal Article
  • Klinisk medicin
  • Knockout
  • Medical and Health Sciences
  • Medical Genetics
  • Medicin och hälsovetenskap
  • Medicinsk genetik
  • Medicinska och farmaceutiska grundvetenskaper
  • meta
  • meta-regression
  • Mice
  • Mice, Knockout
  • musculoskeletal diseases
  • Newborn
  • Non
  • Polymorphism
  • Polymorphism, Single Nucleotide - genetics
  • Preschool
  • pubmedpublicationtype
  • pure
  • Quantitative Trait
  • Quantitative Trait, Heritable
  • RANKL
  • regression
  • Regression Analysis
  • Research Support
  • researchoutput
  • Single Nucleotide
  • total
  • total-body DXA
  • wide association studies
  • Wide Association Study
ispartof: American journal of human genetics, 2018-01-04, Vol.102 (1), p.88-102
description: Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0002-9297
fulltext: fulltext
issn:
  • 0002-9297
  • 1537-6605
url: Link


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titleLife-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
sourceAlma/SFX Local Collection
creatorMedina-Gomez, Carolina ; Kemp, John P ; Trajanoska, Katerina ; Luan, Jian’an ; Chesi, Alessandra ; Ahluwalia, Tarunveer S ; Mook-Kanamori, Dennis O ; Ham, Annelies ; Hartwig, Fernando P ; Evans, Daniel S ; Joro, Raimo ; Nedeljkovic, Ivana ; Zheng, Hou-Feng ; Zhu, Kun ; Atalay, Mustafa ; Liu, Ching-Ti ; Nethander, Maria ; Broer, Linda ; Porleifsson, Gudmar ; Mullin, Benjamin H ; Handelman, Samuel K ; Nalls, Mike A ; Jessen, Leon E ; Heppe, Denise H.M ; Richards, J. Brent ; Wang, Carol ; Chawes, Bo ; Schraut, Katharina E ; Amin, Najaf ; Wareham, Nick ; Karasik, David ; Van der Velde, Nathalie ; Ikram, M. Arfan ; Zemel, Babette S ; Zhou, Yanhua ; Carlsson, Christian J ; Liu, Yongmei ; McGuigan, Fiona E ; Boer, Cindy G ; Bønnelykke, Klaus ; Ralston, Stuart H ; Robbins, John A ; Walsh, John P ; Zillikens, M. Carola ; Langenberg, Claudia ; Li-Gao, Ruifang ; Williams, Frances M.K ; Harris, Tamara B ; Akesson, Kristina ; Jackson, Rebecca D ; Sigurdsson, Gunnar ; den Heijer, Martin ; van der Eerden, Bram C.J ; van de Peppel, Jeroen ; Spector, Timothy D ; Pennell, Craig ; Horta, Bernardo L ; Felix, Janine F ; Zhao, Jing Hua ; Wilson, Scott G ; de Mutsert, Renée ; Bisgaard, Hans ; Styrkársdóttir, Unnur ; Jaddoe, Vincent W ; Orwoll, Eric ; Lakka, Timo A ; Scott, Robert ; Grant, Struan F.A ; Lorentzon, Mattias ; van Duijn, Cornelia M ; Wilson, James F ; Stefansson, Kari ; Psaty, Bruce M ; Kiel, Douglas P ; Ohlsson, Claes ; Ntzani, Evangelia ; van Wijnen, Andre J ; Forgetta, Vincenzo ; Ghanbari, Mohsen ; Logan, John G ; Williams, Graham R ; Bassett, J.H. Duncan ; Croucher, Peter I ; Evangelou, Evangelos ; Uitterlinden, Andre G ; Ackert-Bicknell, Cheryl L ; Tobias, Jonathan H ; Evans, David M ; Rivadeneira, Fernando
creatorcontribMedina-Gomez, Carolina ; Kemp, John P ; Trajanoska, Katerina ; Luan, Jian’an ; Chesi, Alessandra ; Ahluwalia, Tarunveer S ; Mook-Kanamori, Dennis O ; Ham, Annelies ; Hartwig, Fernando P ; Evans, Daniel S ; Joro, Raimo ; Nedeljkovic, Ivana ; Zheng, Hou-Feng ; Zhu, Kun ; Atalay, Mustafa ; Liu, Ching-Ti ; Nethander, Maria ; Broer, Linda ; Porleifsson, Gudmar ; Mullin, Benjamin H ; Handelman, Samuel K ; Nalls, Mike A ; Jessen, Leon E ; Heppe, Denise H.M ; Richards, J. Brent ; Wang, Carol ; Chawes, Bo ; Schraut, Katharina E ; Amin, Najaf ; Wareham, Nick ; Karasik, David ; Van der Velde, Nathalie ; Ikram, M. Arfan ; Zemel, Babette S ; Zhou, Yanhua ; Carlsson, Christian J ; Liu, Yongmei ; McGuigan, Fiona E ; Boer, Cindy G ; Bønnelykke, Klaus ; Ralston, Stuart H ; Robbins, John A ; Walsh, John P ; Zillikens, M. Carola ; Langenberg, Claudia ; Li-Gao, Ruifang ; Williams, Frances M.K ; Harris, Tamara B ; Akesson, Kristina ; Jackson, Rebecca D ; Sigurdsson, Gunnar ; den Heijer, Martin ; van der Eerden, Bram C.J ; van de Peppel, Jeroen ; Spector, Timothy D ; Pennell, Craig ; Horta, Bernardo L ; Felix, Janine F ; Zhao, Jing Hua ; Wilson, Scott G ; de Mutsert, Renée ; Bisgaard, Hans ; Styrkársdóttir, Unnur ; Jaddoe, Vincent W ; Orwoll, Eric ; Lakka, Timo A ; Scott, Robert ; Grant, Struan F.A ; Lorentzon, Mattias ; van Duijn, Cornelia M ; Wilson, James F ; Stefansson, Kari ; Psaty, Bruce M ; Kiel, Douglas P ; Ohlsson, Claes ; Ntzani, Evangelia ; van Wijnen, Andre J ; Forgetta, Vincenzo ; Ghanbari, Mohsen ; Logan, John G ; Williams, Graham R ; Bassett, J.H. Duncan ; Croucher, Peter I ; Evangelou, Evangelos ; Uitterlinden, Andre G ; Ackert-Bicknell, Cheryl L ; Tobias, Jonathan H ; Evans, David M ; Rivadeneira, Fernando ; Göteborgs universitet ; Gothenburg University ; Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition ; Core Facilities, Bioinformatics ; Sahlgrenska Academy ; Centre for Bone and Arthritis Research ; Sahlgrenska akademin ; Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
descriptionBone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.
identifier
0ISSN: 0002-9297
1EISSN: 1537-6605
2DOI: 10.1016/j.ajhg.2017.12.005
3PMID: 29304378
languageeng
publisherUnited States: Elsevier Inc
subject06 Biological Sciences ; 11 Medical And Health Sciences ; Adolescent ; age ; Age Factors ; age-dependent effects ; Analysis ; Animals ; Article ; atira ; Basic Medicine ; BMD ; body DXA ; Bone Density ; Bone Density - genetics ; bone mineral density ; Child ; Child, Preschool ; Clinical Medicine ; CREB3L1 ; dependent effects ; ESR1 ; fracture ; genetic correlation ; Genetic Loci ; Genetic research ; genetics ; Genetics & Heredity ; Genome ; genome-wide association studies ; Genome-Wide Association Study ; Genomics ; Gov't ; GWASs ; Heritable ; Humans ; Infant ; Infant, Newborn ; Journal Article ; Klinisk medicin ; Knockout ; Medical and Health Sciences ; Medical Genetics ; Medicin och hälsovetenskap ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; meta ; meta-regression ; Mice ; Mice, Knockout ; musculoskeletal diseases ; Newborn ; Non ; Polymorphism ; Polymorphism, Single Nucleotide - genetics ; Preschool ; pubmedpublicationtype ; pure ; Quantitative Trait ; Quantitative Trait, Heritable ; RANKL ; regression ; Regression Analysis ; Research Support ; researchoutput ; Single Nucleotide ; total ; total-body DXA ; wide association studies ; Wide Association Study
ispartofAmerican journal of human genetics, 2018-01-04, Vol.102 (1), p.88-102
rights
02017 American Society of Human Genetics
1info:eu-repo/semantics/restrictedAccess
2Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
3COPYRIGHT 2018 Elsevier B.V.
42017 American Society of Human Genetics. 2017 American Society of Human Genetics
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search
creatorcontrib
0Medina-Gomez, Carolina
1Kemp, John P
2Trajanoska, Katerina
3Luan, Jian’an
4Chesi, Alessandra
5Ahluwalia, Tarunveer S
6Mook-Kanamori, Dennis O
7Ham, Annelies
8Hartwig, Fernando P
9Evans, Daniel S
10Joro, Raimo
11Nedeljkovic, Ivana
12Zheng, Hou-Feng
13Zhu, Kun
14Atalay, Mustafa
15Liu, Ching-Ti
16Nethander, Maria
17Broer, Linda
18Porleifsson, Gudmar
19Mullin, Benjamin H
20Handelman, Samuel K
21Nalls, Mike A
22Jessen, Leon E
23Heppe, Denise H.M
24Richards, J. Brent
25Wang, Carol
26Chawes, Bo
27Schraut, Katharina E
28Amin, Najaf
29Wareham, Nick
30Karasik, David
31Van der Velde, Nathalie
32Ikram, M. Arfan
33Zemel, Babette S
34Zhou, Yanhua
35Carlsson, Christian J
36Liu, Yongmei
37McGuigan, Fiona E
38Boer, Cindy G
39Bønnelykke, Klaus
40Ralston, Stuart H
41Robbins, John A
42Walsh, John P
43Zillikens, M. Carola
44Langenberg, Claudia
45Li-Gao, Ruifang
46Williams, Frances M.K
47Harris, Tamara B
48Akesson, Kristina
49Jackson, Rebecca D
50Sigurdsson, Gunnar
51den Heijer, Martin
52van der Eerden, Bram C.J
53van de Peppel, Jeroen
54Spector, Timothy D
55Pennell, Craig
56Horta, Bernardo L
57Felix, Janine F
58Zhao, Jing Hua
59Wilson, Scott G
60de Mutsert, Renée
61Bisgaard, Hans
62Styrkársdóttir, Unnur
63Jaddoe, Vincent W
64Orwoll, Eric
65Lakka, Timo A
66Scott, Robert
67Grant, Struan F.A
68Lorentzon, Mattias
69van Duijn, Cornelia M
70Wilson, James F
71Stefansson, Kari
72Psaty, Bruce M
73Kiel, Douglas P
74Ohlsson, Claes
75Ntzani, Evangelia
76van Wijnen, Andre J
77Forgetta, Vincenzo
78Ghanbari, Mohsen
79Logan, John G
80Williams, Graham R
81Bassett, J.H. Duncan
82Croucher, Peter I
83Evangelou, Evangelos
84Uitterlinden, Andre G
85Ackert-Bicknell, Cheryl L
86Tobias, Jonathan H
87Evans, David M
88Rivadeneira, Fernando
89Göteborgs universitet
90Gothenburg University
91Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
92Core Facilities, Bioinformatics
93Sahlgrenska Academy
94Centre for Bone and Arthritis Research
95Sahlgrenska akademin
96Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
title
0Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
1American journal of human genetics
addtitleAm J Hum Genet
descriptionBone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.
subject
006 Biological Sciences
111 Medical And Health Sciences
2Adolescent
3age
4Age Factors
5age-dependent effects
6Analysis
7Animals
8Article
9atira
10Basic Medicine
11BMD
12body DXA
13Bone Density
14Bone Density - genetics
15bone mineral density
16Child
17Child, Preschool
18Clinical Medicine
19CREB3L1
20dependent effects
21ESR1
22fracture
23genetic correlation
24Genetic Loci
25Genetic research
26genetics
27Genetics & Heredity
28Genome
29genome-wide association studies
30Genome-Wide Association Study
31Genomics
32Gov't
33GWASs
34Heritable
35Humans
36Infant
37Infant, Newborn
38Journal Article
39Klinisk medicin
40Knockout
41Medical and Health Sciences
42Medical Genetics
43Medicin och hälsovetenskap
44Medicinsk genetik
45Medicinska och farmaceutiska grundvetenskaper
46meta
47meta-regression
48Mice
49Mice, Knockout
50musculoskeletal diseases
51Newborn
52Non
53Polymorphism
54Polymorphism, Single Nucleotide - genetics
55Preschool
56pubmedpublicationtype
57pure
58Quantitative Trait
59Quantitative Trait, Heritable
60RANKL
61regression
62Regression Analysis
63Research Support
64researchoutput
65Single Nucleotide
66total
67total-body DXA
68wide association studies
69Wide Association Study
issn
00002-9297
11537-6605
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creationdate2018
recordtypearticle
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startdate20180104
enddate20180104
creator
0Medina-Gomez, Carolina
1Kemp, John P
2Trajanoska, Katerina
3Luan, Jian’an
4Chesi, Alessandra
5Ahluwalia, Tarunveer S
6Mook-Kanamori, Dennis O
7Ham, Annelies
8Hartwig, Fernando P
9Evans, Daniel S
10Joro, Raimo
11Nedeljkovic, Ivana
12Zheng, Hou-Feng
13Zhu, Kun
14Atalay, Mustafa
15Liu, Ching-Ti
16Nethander, Maria
17Broer, Linda
18Porleifsson, Gudmar
19Mullin, Benjamin H
20Handelman, Samuel K
21Nalls, Mike A
22Jessen, Leon E
23Heppe, Denise H.M
24Richards, J. Brent
25Wang, Carol
26Chawes, Bo
27Schraut, Katharina E
28Amin, Najaf
29Wareham, Nick
30Karasik, David
31Van der Velde, Nathalie
32Ikram, M. Arfan
33Zemel, Babette S
34Zhou, Yanhua
35Carlsson, Christian J
36Liu, Yongmei
37McGuigan, Fiona E
38Boer, Cindy G
39Bønnelykke, Klaus
40Ralston, Stuart H
41Robbins, John A
42Walsh, John P
43Zillikens, M. Carola
44Langenberg, Claudia
45Li-Gao, Ruifang
46Williams, Frances M.K
47Harris, Tamara B
48Akesson, Kristina
49Jackson, Rebecca D
50Sigurdsson, Gunnar
51den Heijer, Martin
52van der Eerden, Bram C.J
53van de Peppel, Jeroen
54Spector, Timothy D
55Pennell, Craig
56Horta, Bernardo L
57Felix, Janine F
58Zhao, Jing Hua
59Wilson, Scott G
60de Mutsert, Renée
61Bisgaard, Hans
62Styrkársdóttir, Unnur
63Jaddoe, Vincent W
64Orwoll, Eric
65Lakka, Timo A
66Scott, Robert
67Grant, Struan F.A
68Lorentzon, Mattias
69van Duijn, Cornelia M
70Wilson, James F
71Stefansson, Kari
72Psaty, Bruce M
73Kiel, Douglas P
74Ohlsson, Claes
75Ntzani, Evangelia
76van Wijnen, Andre J
77Forgetta, Vincenzo
78Ghanbari, Mohsen
79Logan, John G
80Williams, Graham R
81Bassett, J.H. Duncan
82Croucher, Peter I
83Evangelou, Evangelos
84Uitterlinden, Andre G
85Ackert-Bicknell, Cheryl L
86Tobias, Jonathan H
87Evans, David M
88Rivadeneira, Fernando
general
0Elsevier Inc
1Elsevier B.V
2Elsevier
scope
06I.
1AAFTH
25DI
35DJ
4QVL
5CGR
6CUY
7CVF
8ECM
9EIF
10NPM
11AAYXX
12CITATION
13BKMMT
14BSHEE
157X8
16BOBZL
17CLFQK
185PM
19ADTPV
20AOWAS
21D95
sort
creationdate20180104
titleLife-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
authorMedina-Gomez, Carolina ; Kemp, John P ; Trajanoska, Katerina ; Luan, Jian’an ; Chesi, Alessandra ; Ahluwalia, Tarunveer S ; Mook-Kanamori, Dennis O ; Ham, Annelies ; Hartwig, Fernando P ; Evans, Daniel S ; Joro, Raimo ; Nedeljkovic, Ivana ; Zheng, Hou-Feng ; Zhu, Kun ; Atalay, Mustafa ; Liu, Ching-Ti ; Nethander, Maria ; Broer, Linda ; Porleifsson, Gudmar ; Mullin, Benjamin H ; Handelman, Samuel K ; Nalls, Mike A ; Jessen, Leon E ; Heppe, Denise H.M ; Richards, J. Brent ; Wang, Carol ; Chawes, Bo ; Schraut, Katharina E ; Amin, Najaf ; Wareham, Nick ; Karasik, David ; Van der Velde, Nathalie ; Ikram, M. Arfan ; Zemel, Babette S ; Zhou, Yanhua ; Carlsson, Christian J ; Liu, Yongmei ; McGuigan, Fiona E ; Boer, Cindy G ; Bønnelykke, Klaus ; Ralston, Stuart H ; Robbins, John A ; Walsh, John P ; Zillikens, M. Carola ; Langenberg, Claudia ; Li-Gao, Ruifang ; Williams, Frances M.K ; Harris, Tamara B ; Akesson, Kristina ; Jackson, Rebecca D ; Sigurdsson, Gunnar ; den Heijer, Martin ; van der Eerden, Bram C.J ; van de Peppel, Jeroen ; Spector, Timothy D ; Pennell, Craig ; Horta, Bernardo L ; Felix, Janine F ; Zhao, Jing Hua ; Wilson, Scott G ; de Mutsert, Renée ; Bisgaard, Hans ; Styrkársdóttir, Unnur ; Jaddoe, Vincent W ; Orwoll, Eric ; Lakka, Timo A ; Scott, Robert ; Grant, Struan F.A ; Lorentzon, Mattias ; van Duijn, Cornelia M ; Wilson, James F ; Stefansson, Kari ; Psaty, Bruce M ; Kiel, Douglas P ; Ohlsson, Claes ; Ntzani, Evangelia ; van Wijnen, Andre J ; Forgetta, Vincenzo ; Ghanbari, Mohsen ; Logan, John G ; Williams, Graham R ; Bassett, J.H. Duncan ; Croucher, Peter I ; Evangelou, Evangelos ; Uitterlinden, Andre G ; Ackert-Bicknell, Cheryl L ; Tobias, Jonathan H ; Evans, David M ; Rivadeneira, Fernando
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1786t-dac1e932e585443704fbf69799361b45abcf17829fc5baed9097849047c930883
rsrctypearticles
prefilterarticles
languageeng
creationdate2018
topic
006 Biological Sciences
111 Medical And Health Sciences
2Adolescent
3age
4Age Factors
5age-dependent effects
6Analysis
7Animals
8Article
9atira
10Basic Medicine
11BMD
12body DXA
13Bone Density
14Bone Density - genetics
15bone mineral density
16Child
17Child, Preschool
18Clinical Medicine
19CREB3L1
20dependent effects
21ESR1
22fracture
23genetic correlation
24Genetic Loci
25Genetic research
26genetics
27Genetics & Heredity
28Genome
29genome-wide association studies
30Genome-Wide Association Study
31Genomics
32Gov't
33GWASs
34Heritable
35Humans
36Infant
37Infant, Newborn
38Journal Article
39Klinisk medicin
40Knockout
41Medical and Health Sciences
42Medical Genetics
43Medicin och hälsovetenskap
44Medicinsk genetik
45Medicinska och farmaceutiska grundvetenskaper
46meta
47meta-regression
48Mice
49Mice, Knockout
50musculoskeletal diseases
51Newborn
52Non
53Polymorphism
54Polymorphism, Single Nucleotide - genetics
55Preschool
56pubmedpublicationtype
57pure
58Quantitative Trait
59Quantitative Trait, Heritable
60RANKL
61regression
62Regression Analysis
63Research Support
64researchoutput
65Single Nucleotide
66total
67total-body DXA
68wide association studies
69Wide Association Study
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Medina-Gomez, Carolina
1Kemp, John P
2Trajanoska, Katerina
3Luan, Jian’an
4Chesi, Alessandra
5Ahluwalia, Tarunveer S
6Mook-Kanamori, Dennis O
7Ham, Annelies
8Hartwig, Fernando P
9Evans, Daniel S
10Joro, Raimo
11Nedeljkovic, Ivana
12Zheng, Hou-Feng
13Zhu, Kun
14Atalay, Mustafa
15Liu, Ching-Ti
16Nethander, Maria
17Broer, Linda
18Porleifsson, Gudmar
19Mullin, Benjamin H
20Handelman, Samuel K
21Nalls, Mike A
22Jessen, Leon E
23Heppe, Denise H.M
24Richards, J. Brent
25Wang, Carol
26Chawes, Bo
27Schraut, Katharina E
28Amin, Najaf
29Wareham, Nick
30Karasik, David
31Van der Velde, Nathalie
32Ikram, M. Arfan
33Zemel, Babette S
34Zhou, Yanhua
35Carlsson, Christian J
36Liu, Yongmei
37McGuigan, Fiona E
38Boer, Cindy G
39Bønnelykke, Klaus
40Ralston, Stuart H
41Robbins, John A
42Walsh, John P
43Zillikens, M. Carola
44Langenberg, Claudia
45Li-Gao, Ruifang
46Williams, Frances M.K
47Harris, Tamara B
48Akesson, Kristina
49Jackson, Rebecca D
50Sigurdsson, Gunnar
51den Heijer, Martin
52van der Eerden, Bram C.J
53van de Peppel, Jeroen
54Spector, Timothy D
55Pennell, Craig
56Horta, Bernardo L
57Felix, Janine F
58Zhao, Jing Hua
59Wilson, Scott G
60de Mutsert, Renée
61Bisgaard, Hans
62Styrkársdóttir, Unnur
63Jaddoe, Vincent W
64Orwoll, Eric
65Lakka, Timo A
66Scott, Robert
67Grant, Struan F.A
68Lorentzon, Mattias
69van Duijn, Cornelia M
70Wilson, James F
71Stefansson, Kari
72Psaty, Bruce M
73Kiel, Douglas P
74Ohlsson, Claes
75Ntzani, Evangelia
76van Wijnen, Andre J
77Forgetta, Vincenzo
78Ghanbari, Mohsen
79Logan, John G
80Williams, Graham R
81Bassett, J.H. Duncan
82Croucher, Peter I
83Evangelou, Evangelos
84Uitterlinden, Andre G
85Ackert-Bicknell, Cheryl L
86Tobias, Jonathan H
87Evans, David M
88Rivadeneira, Fernando
89Göteborgs universitet
90Gothenburg University
91Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
92Core Facilities, Bioinformatics
93Sahlgrenska Academy
94Centre for Bone and Arthritis Research
95Sahlgrenska akademin
96Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
collection
0ScienceDirect Open Access Titles
1Elsevier:ScienceDirect:Open Access
2NARCIS
3NARCIS: Datasets
4NARCIS:Publications
5Medline
6MEDLINE
7MEDLINE (Ovid)
8MEDLINE
9MEDLINE
10PubMed
11CrossRef
12Gale General OneFile (A&I only)
13Academic OneFile (A&I only)
14MEDLINE - Academic
15OpenAIRE (Open Access)
16OpenAIRE
17PubMed Central (Full Participant titles)
18SwePub
19SwePub Articles
20SWEPUB Lunds universitet
jtitleAmerican journal of human genetics
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Medina-Gomez, Carolina
1Kemp, John P
2Trajanoska, Katerina
3Luan, Jian’an
4Chesi, Alessandra
5Ahluwalia, Tarunveer S
6Mook-Kanamori, Dennis O
7Ham, Annelies
8Hartwig, Fernando P
9Evans, Daniel S
10Joro, Raimo
11Nedeljkovic, Ivana
12Zheng, Hou-Feng
13Zhu, Kun
14Atalay, Mustafa
15Liu, Ching-Ti
16Nethander, Maria
17Broer, Linda
18Porleifsson, Gudmar
19Mullin, Benjamin H
20Handelman, Samuel K
21Nalls, Mike A
22Jessen, Leon E
23Heppe, Denise H.M
24Richards, J. Brent
25Wang, Carol
26Chawes, Bo
27Schraut, Katharina E
28Amin, Najaf
29Wareham, Nick
30Karasik, David
31Van der Velde, Nathalie
32Ikram, M. Arfan
33Zemel, Babette S
34Zhou, Yanhua
35Carlsson, Christian J
36Liu, Yongmei
37McGuigan, Fiona E
38Boer, Cindy G
39Bønnelykke, Klaus
40Ralston, Stuart H
41Robbins, John A
42Walsh, John P
43Zillikens, M. Carola
44Langenberg, Claudia
45Li-Gao, Ruifang
46Williams, Frances M.K
47Harris, Tamara B
48Akesson, Kristina
49Jackson, Rebecca D
50Sigurdsson, Gunnar
51den Heijer, Martin
52van der Eerden, Bram C.J
53van de Peppel, Jeroen
54Spector, Timothy D
55Pennell, Craig
56Horta, Bernardo L
57Felix, Janine F
58Zhao, Jing Hua
59Wilson, Scott G
60de Mutsert, Renée
61Bisgaard, Hans
62Styrkársdóttir, Unnur
63Jaddoe, Vincent W
64Orwoll, Eric
65Lakka, Timo A
66Scott, Robert
67Grant, Struan F.A
68Lorentzon, Mattias
69van Duijn, Cornelia M
70Wilson, James F
71Stefansson, Kari
72Psaty, Bruce M
73Kiel, Douglas P
74Ohlsson, Claes
75Ntzani, Evangelia
76van Wijnen, Andre J
77Forgetta, Vincenzo
78Ghanbari, Mohsen
79Logan, John G
80Williams, Graham R
81Bassett, J.H. Duncan
82Croucher, Peter I
83Evangelou, Evangelos
84Uitterlinden, Andre G
85Ackert-Bicknell, Cheryl L
86Tobias, Jonathan H
87Evans, David M
88Rivadeneira, Fernando
aucorp
0Göteborgs universitet
1Gothenburg University
2Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
3Core Facilities, Bioinformatics
4Sahlgrenska Academy
5Centre for Bone and Arthritis Research
6Sahlgrenska akademin
7Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
formatjournal
genrearticle
ristypeJOUR
atitleLife-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
jtitleAmerican journal of human genetics
addtitleAm J Hum Genet
date2018-01-04
risdate2018
volume102
issue1
spage88
epage102
pages88-102
issn0002-9297
eissn1537-6605
notesThese authors contributed equally
abstractBone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.
copUnited States
pubElsevier Inc
pmid29304378
doi10.1016/j.ajhg.2017.12.005
oafree_for_read