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Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), wa... Full description

Journal Title: American journal of human genetics 2019, Vol.104 (1), p.112-138
Main Author: Kraja, Aldi T
Other Authors: Fetterman, Jessica L , Graff, Mariaelisa , Have, Christian Theil , Yanek, Lisa R , Arking, Dan E , Chasman, Daniel I , Young, Kristin , Ligthart, Symen , Hill, W. David , Weiss, Stefan , Luan, Jian’an , Giulianini, Franco , Hartwig, Fernando P , Lin, Shiow J , Wang, Lihua , Richardson, Tom G , Ghanbari, Mohsen , Wojczynski, Mary K , Lee, Wen-Jane , Armasu, Sebastian M , Barve, Ruteja A , Ryan, Kathleen A , An, Ping , Bielinski, Suzette J , Bowden, Donald W , Broeckel, Ulrich , Chu, Audrey Y , Corley, Janie , Cox, Simon R , Uitterlinden, Andre G , Rivadeneira, Fernando , Daw, E. Warwick , de las Fuentes, Lisa , Gao, He , Ahluwalia, Tarunveer S , de Mutsert, Renée , Emery, Leslie S , Erzurumluoglu, A. Mesut , Perry, James A , Fu, Mao , Forouhi, Nita G , Gu, Zhenglong , Harris, Sarah E , Irvin, Marguerite R , Jonsson, Anna E , Kerrison, Nicola D , Larson, Nicholas B , Lin, Keng-Hung , Mathias, Rasika A , Lee, Joseph H , Nauck, Matthias , Pankow, James , Patki, Amit , Qi, Qibin , Sofer, Tamar , Starr, John M , de Haan, Hugoline G , Wang, Yujie , Weeke, Peter E , Wu, Hongsheng , Yang, Wei , Zeng, Donglin , Witte, Daniel R , Weir, Bruce S , Wareham, Nicholas J , Vestergaard, Henrik , Turner, Stephen T , Torp-Pedersen, Christian , Stergiakouli, Evie , Ikram, M. Arfan , Franco, Oscar H , Ridker, Paul M , Pedersen, Oluf , Nohr, Ellen A , Newman, Anne B , Linneberg, Allan , Langenberg, Claudia , Kilpeläinen, Tuomas O , Kardia, Sharon L.R , Jørgensen, Torben , Homuth, Georg , Hansen, Torben , Goodarzi, Mark O , Deary, Ian J , Christensen, Cramer , Chen, Yii-Der Ida , Bonnelykke, Klaus , Rodriguez, Santiago , Davies, Gail , Horta, Bernardo L , Thyagarajan, Bharat , Grarup, Niels , Guo, Xiuqing , Tiwari, Hemant K , Malik, Afshan N , Scott, Robert A , de Andrade, Mariza , Province, Michael A , Rotter, Jerome I
Format: Electronic Article Electronic Article
Language: English
Subjects:
BMI
Quelle: Alma/SFX Local Collection
Publisher: United States: Elsevier Inc
ID: ISSN: 0002-9297
Link: https://www.ncbi.nlm.nih.gov/pubmed/30595373
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6323610
title: Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits
format: Article
creator:
  • Kraja, Aldi T
  • Fetterman, Jessica L
  • Graff, Mariaelisa
  • Have, Christian Theil
  • Yanek, Lisa R
  • Arking, Dan E
  • Chasman, Daniel I
  • Young, Kristin
  • Ligthart, Symen
  • Hill, W. David
  • Weiss, Stefan
  • Luan, Jian’an
  • Giulianini, Franco
  • Hartwig, Fernando P
  • Lin, Shiow J
  • Wang, Lihua
  • Richardson, Tom G
  • Ghanbari, Mohsen
  • Wojczynski, Mary K
  • Lee, Wen-Jane
  • Armasu, Sebastian M
  • Barve, Ruteja A
  • Ryan, Kathleen A
  • An, Ping
  • Bielinski, Suzette J
  • Bowden, Donald W
  • Broeckel, Ulrich
  • Chu, Audrey Y
  • Corley, Janie
  • Cox, Simon R
  • Uitterlinden, Andre G
  • Rivadeneira, Fernando
  • Daw, E. Warwick
  • de las Fuentes, Lisa
  • Gao, He
  • Ahluwalia, Tarunveer S
  • de Mutsert, Renée
  • Emery, Leslie S
  • Erzurumluoglu, A. Mesut
  • Perry, James A
  • Fu, Mao
  • Forouhi, Nita G
  • Gu, Zhenglong
  • Harris, Sarah E
  • Irvin, Marguerite R
  • Jonsson, Anna E
  • Kerrison, Nicola D
  • Larson, Nicholas B
  • Lin, Keng-Hung
  • Mathias, Rasika A
  • Lee, Joseph H
  • Nauck, Matthias
  • Pankow, James
  • Patki, Amit
  • Qi, Qibin
  • Sofer, Tamar
  • Starr, John M
  • de Haan, Hugoline G
  • Wang, Yujie
  • Weeke, Peter E
  • Wu, Hongsheng
  • Yang, Wei
  • Zeng, Donglin
  • Witte, Daniel R
  • Weir, Bruce S
  • Wareham, Nicholas J
  • Vestergaard, Henrik
  • Turner, Stephen T
  • Torp-Pedersen, Christian
  • Stergiakouli, Evie
  • Ikram, M. Arfan
  • Franco, Oscar H
  • Ridker, Paul M
  • Pedersen, Oluf
  • Nohr, Ellen A
  • Newman, Anne B
  • Linneberg, Allan
  • Langenberg, Claudia
  • Kilpeläinen, Tuomas O
  • Kardia, Sharon L.R
  • Jørgensen, Torben
  • Homuth, Georg
  • Hansen, Torben
  • Goodarzi, Mark O
  • Deary, Ian J
  • Christensen, Cramer
  • Chen, Yii-Der Ida
  • Bonnelykke, Klaus
  • Rodriguez, Santiago
  • Davies, Gail
  • Horta, Bernardo L
  • Thyagarajan, Bharat
  • Grarup, Niels
  • Guo, Xiuqing
  • Tiwari, Hemant K
  • Malik, Afshan N
  • Scott, Robert A
  • de Andrade, Mariza
  • Province, Michael A
  • Rotter, Jerome I
subjects:
  • Adipocytes - metabolism
  • BMI
  • Body Mass Index
  • Cardiovascular Diseases - genetics
  • Cardiovascular Diseases - metabolism
  • Cohort Studies
  • Diabetes Mellitus - genetics
  • Diabetes Mellitus - metabolism
  • DNA, Mitochondrial - genetics
  • Genes, Mitochondrial - genetics
  • Genetic aspects
  • Genetic Variation - genetics
  • Genome-wide association studies
  • glucose
  • Glucose - metabolism
  • Glycated Hemoglobin A - metabolism
  • HbA1c
  • HOMA-B
  • HOMA-IR
  • Humans
  • insulin
  • Insulin - metabolism
  • Metabolic diseases
  • Metabolism - genetics
  • mitochondria
  • Mitochondria - genetics
  • Mitochondria - metabolism
  • Mitochondrial DNA
  • MT-nDNA candidate genes
  • mtDNA
  • Physiological aspects
  • Quantitative Trait Loci
  • Risk factors
  • Usage
  • Waist-Hip Ratio
  • waist-to-hip ratio
ispartof: American journal of human genetics, 2019, Vol.104 (1), p.112-138
description: Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E−04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E−03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia’s genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E−06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0002-9297
fulltext: fulltext
issn:
  • 0002-9297
  • 1537-6605
url: Link


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titleAssociations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits
sourceAlma/SFX Local Collection
creatorKraja, Aldi T ; Fetterman, Jessica L ; Graff, Mariaelisa ; Have, Christian Theil ; Yanek, Lisa R ; Arking, Dan E ; Chasman, Daniel I ; Young, Kristin ; Ligthart, Symen ; Hill, W. David ; Weiss, Stefan ; Luan, Jian’an ; Giulianini, Franco ; Hartwig, Fernando P ; Lin, Shiow J ; Wang, Lihua ; Richardson, Tom G ; Ghanbari, Mohsen ; Wojczynski, Mary K ; Lee, Wen-Jane ; Armasu, Sebastian M ; Barve, Ruteja A ; Ryan, Kathleen A ; An, Ping ; Bielinski, Suzette J ; Bowden, Donald W ; Broeckel, Ulrich ; Chu, Audrey Y ; Corley, Janie ; Cox, Simon R ; Uitterlinden, Andre G ; Rivadeneira, Fernando ; Daw, E. Warwick ; de las Fuentes, Lisa ; Gao, He ; Ahluwalia, Tarunveer S ; de Mutsert, Renée ; Emery, Leslie S ; Erzurumluoglu, A. Mesut ; Perry, James A ; Fu, Mao ; Forouhi, Nita G ; Gu, Zhenglong ; Harris, Sarah E ; Irvin, Marguerite R ; Jonsson, Anna E ; Kerrison, Nicola D ; Larson, Nicholas B ; Lin, Keng-Hung ; Mathias, Rasika A ; Lee, Joseph H ; Nauck, Matthias ; Pankow, James ; Patki, Amit ; Qi, Qibin ; Sofer, Tamar ; Starr, John M ; de Haan, Hugoline G ; Wang, Yujie ; Weeke, Peter E ; Wu, Hongsheng ; Yang, Wei ; Zeng, Donglin ; Witte, Daniel R ; Weir, Bruce S ; Wareham, Nicholas J ; Vestergaard, Henrik ; Turner, Stephen T ; Torp-Pedersen, Christian ; Stergiakouli, Evie ; Ikram, M. Arfan ; Franco, Oscar H ; Ridker, Paul M ; Pedersen, Oluf ; Nohr, Ellen A ; Newman, Anne B ; Linneberg, Allan ; Langenberg, Claudia ; Kilpeläinen, Tuomas O ; Kardia, Sharon L.R ; Jørgensen, Torben ; Homuth, Georg ; Hansen, Torben ; Goodarzi, Mark O ; Deary, Ian J ; Christensen, Cramer ; Chen, Yii-Der Ida ; Bonnelykke, Klaus ; Rodriguez, Santiago ; Davies, Gail ; Horta, Bernardo L ; Thyagarajan, Bharat ; Grarup, Niels ; Guo, Xiuqing ; Tiwari, Hemant K ; Malik, Afshan N ; Scott, Robert A ; de Andrade, Mariza ; Province, Michael A ; Rotter, Jerome I
creatorcontribKraja, Aldi T ; Fetterman, Jessica L ; Graff, Mariaelisa ; Have, Christian Theil ; Yanek, Lisa R ; Arking, Dan E ; Chasman, Daniel I ; Young, Kristin ; Ligthart, Symen ; Hill, W. David ; Weiss, Stefan ; Luan, Jian’an ; Giulianini, Franco ; Hartwig, Fernando P ; Lin, Shiow J ; Wang, Lihua ; Richardson, Tom G ; Ghanbari, Mohsen ; Wojczynski, Mary K ; Lee, Wen-Jane ; Armasu, Sebastian M ; Barve, Ruteja A ; Ryan, Kathleen A ; An, Ping ; Bielinski, Suzette J ; Bowden, Donald W ; Broeckel, Ulrich ; Chu, Audrey Y ; Corley, Janie ; Cox, Simon R ; Uitterlinden, Andre G ; Rivadeneira, Fernando ; Daw, E. Warwick ; de las Fuentes, Lisa ; Gao, He ; Ahluwalia, Tarunveer S ; de Mutsert, Renée ; Emery, Leslie S ; Erzurumluoglu, A. Mesut ; Perry, James A ; Fu, Mao ; Forouhi, Nita G ; Gu, Zhenglong ; Harris, Sarah E ; Irvin, Marguerite R ; Jonsson, Anna E ; Kerrison, Nicola D ; Larson, Nicholas B ; Lin, Keng-Hung ; Mathias, Rasika A ; Lee, Joseph H ; Nauck, Matthias ; Pankow, James ; Patki, Amit ; Qi, Qibin ; Sofer, Tamar ; Starr, John M ; de Haan, Hugoline G ; Wang, Yujie ; Weeke, Peter E ; Wu, Hongsheng ; Yang, Wei ; Zeng, Donglin ; Witte, Daniel R ; Weir, Bruce S ; Wareham, Nicholas J ; Vestergaard, Henrik ; Turner, Stephen T ; Torp-Pedersen, Christian ; Stergiakouli, Evie ; Ikram, M. Arfan ; Franco, Oscar H ; Ridker, Paul M ; Pedersen, Oluf ; Nohr, Ellen A ; Newman, Anne B ; Linneberg, Allan ; Langenberg, Claudia ; Kilpeläinen, Tuomas O ; Kardia, Sharon L.R ; Jørgensen, Torben ; Homuth, Georg ; Hansen, Torben ; Goodarzi, Mark O ; Deary, Ian J ; Christensen, Cramer ; Chen, Yii-Der Ida ; Bonnelykke, Klaus ; Rodriguez, Santiago ; Davies, Gail ; Horta, Bernardo L ; Thyagarajan, Bharat ; Grarup, Niels ; Guo, Xiuqing ; Tiwari, Hemant K ; Malik, Afshan N ; Scott, Robert A ; de Andrade, Mariza ; Province, Michael A ; Rotter, Jerome I
descriptionMitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E−04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E−03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia’s genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E−06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.
identifier
0ISSN: 0002-9297
1EISSN: 1537-6605
2DOI: 10.1016/j.ajhg.2018.12.001
3PMID: 30595373
languageeng
publisherUnited States: Elsevier Inc
subjectAdipocytes - metabolism ; BMI ; Body Mass Index ; Cardiovascular Diseases - genetics ; Cardiovascular Diseases - metabolism ; Cohort Studies ; Diabetes Mellitus - genetics ; Diabetes Mellitus - metabolism ; DNA, Mitochondrial - genetics ; Genes, Mitochondrial - genetics ; Genetic aspects ; Genetic Variation - genetics ; Genome-wide association studies ; glucose ; Glucose - metabolism ; Glycated Hemoglobin A - metabolism ; HbA1c ; HOMA-B ; HOMA-IR ; Humans ; insulin ; Insulin - metabolism ; Metabolic diseases ; Metabolism - genetics ; mitochondria ; Mitochondria - genetics ; Mitochondria - metabolism ; Mitochondrial DNA ; MT-nDNA candidate genes ; mtDNA ; Physiological aspects ; Quantitative Trait Loci ; Risk factors ; Usage ; Waist-Hip Ratio ; waist-to-hip ratio
ispartofAmerican journal of human genetics, 2019, Vol.104 (1), p.112-138
rights
02019 The authors
1info:eu-repo/semantics/restrictedAccess
2Copyright © 2018 American Society of Human Genetics. All rights reserved.
3COPYRIGHT 2019 Elsevier B.V.
42018 American Society of Human Genetics. 2018 American Society of Human Genetics
lds50peer_reviewed
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creatorcontrib
0Kraja, Aldi T
1Fetterman, Jessica L
2Graff, Mariaelisa
3Have, Christian Theil
4Yanek, Lisa R
5Arking, Dan E
6Chasman, Daniel I
7Young, Kristin
8Ligthart, Symen
9Hill, W. David
10Weiss, Stefan
11Luan, Jian’an
12Giulianini, Franco
13Hartwig, Fernando P
14Lin, Shiow J
15Wang, Lihua
16Richardson, Tom G
17Ghanbari, Mohsen
18Wojczynski, Mary K
19Lee, Wen-Jane
20Armasu, Sebastian M
21Barve, Ruteja A
22Ryan, Kathleen A
23An, Ping
24Bielinski, Suzette J
25Bowden, Donald W
26Broeckel, Ulrich
27Chu, Audrey Y
28Corley, Janie
29Cox, Simon R
30Uitterlinden, Andre G
31Rivadeneira, Fernando
32Daw, E. Warwick
33de las Fuentes, Lisa
34Gao, He
35Ahluwalia, Tarunveer S
36de Mutsert, Renée
37Emery, Leslie S
38Erzurumluoglu, A. Mesut
39Perry, James A
40Fu, Mao
41Forouhi, Nita G
42Gu, Zhenglong
43Harris, Sarah E
44Irvin, Marguerite R
45Jonsson, Anna E
46Kerrison, Nicola D
47Larson, Nicholas B
48Lin, Keng-Hung
49Mathias, Rasika A
50Lee, Joseph H
51Nauck, Matthias
52Pankow, James
53Patki, Amit
54Qi, Qibin
55Sofer, Tamar
56Starr, John M
57de Haan, Hugoline G
58Wang, Yujie
59Weeke, Peter E
60Wu, Hongsheng
61Yang, Wei
62Zeng, Donglin
63Witte, Daniel R
64Weir, Bruce S
65Wareham, Nicholas J
66Vestergaard, Henrik
67Turner, Stephen T
68Torp-Pedersen, Christian
69Stergiakouli, Evie
70Ikram, M. Arfan
71Franco, Oscar H
72Ridker, Paul M
73Pedersen, Oluf
74Nohr, Ellen A
75Newman, Anne B
76Linneberg, Allan
77Langenberg, Claudia
78Kilpeläinen, Tuomas O
79Kardia, Sharon L.R
80Jørgensen, Torben
81Homuth, Georg
82Hansen, Torben
83Goodarzi, Mark O
84Deary, Ian J
85Christensen, Cramer
86Chen, Yii-Der Ida
87Bonnelykke, Klaus
88Rodriguez, Santiago
89Davies, Gail
90Horta, Bernardo L
91Thyagarajan, Bharat
92Grarup, Niels
93Guo, Xiuqing
94Tiwari, Hemant K
95Malik, Afshan N
96Scott, Robert A
97de Andrade, Mariza
98Province, Michael A
99Rotter, Jerome I
title
0Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits
1American journal of human genetics
addtitleAm J Hum Genet
descriptionMitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E−04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E−03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia’s genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E−06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.
subject
0Adipocytes - metabolism
1BMI
2Body Mass Index
3Cardiovascular Diseases - genetics
4Cardiovascular Diseases - metabolism
5Cohort Studies
6Diabetes Mellitus - genetics
7Diabetes Mellitus - metabolism
8DNA, Mitochondrial - genetics
9Genes, Mitochondrial - genetics
10Genetic aspects
11Genetic Variation - genetics
12Genome-wide association studies
13glucose
14Glucose - metabolism
15Glycated Hemoglobin A - metabolism
16HbA1c
17HOMA-B
18HOMA-IR
19Humans
20insulin
21Insulin - metabolism
22Metabolic diseases
23Metabolism - genetics
24mitochondria
25Mitochondria - genetics
26Mitochondria - metabolism
27Mitochondrial DNA
28MT-nDNA candidate genes
29mtDNA
30Physiological aspects
31Quantitative Trait Loci
32Risk factors
33Usage
34Waist-Hip Ratio
35waist-to-hip ratio
issn
00002-9297
11537-6605
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0Kraja, Aldi T
1Fetterman, Jessica L
2Graff, Mariaelisa
3Have, Christian Theil
4Yanek, Lisa R
5Arking, Dan E
6Chasman, Daniel I
7Young, Kristin
8Ligthart, Symen
9Hill, W. David
10Weiss, Stefan
11Luan, Jian’an
12Giulianini, Franco
13Hartwig, Fernando P
14Lin, Shiow J
15Wang, Lihua
16Richardson, Tom G
17Ghanbari, Mohsen
18Wojczynski, Mary K
19Lee, Wen-Jane
20Armasu, Sebastian M
21Barve, Ruteja A
22Ryan, Kathleen A
23An, Ping
24Bielinski, Suzette J
25Bowden, Donald W
26Broeckel, Ulrich
27Chu, Audrey Y
28Corley, Janie
29Cox, Simon R
30Uitterlinden, Andre G
31Rivadeneira, Fernando
32Daw, E. Warwick
33de las Fuentes, Lisa
34Gao, He
35Ahluwalia, Tarunveer S
36de Mutsert, Renée
37Emery, Leslie S
38Erzurumluoglu, A. Mesut
39Perry, James A
40Fu, Mao
41Forouhi, Nita G
42Gu, Zhenglong
43Harris, Sarah E
44Irvin, Marguerite R
45Jonsson, Anna E
46Kerrison, Nicola D
47Larson, Nicholas B
48Lin, Keng-Hung
49Mathias, Rasika A
50Lee, Joseph H
51Nauck, Matthias
52Pankow, James
53Patki, Amit
54Qi, Qibin
55Sofer, Tamar
56Starr, John M
57de Haan, Hugoline G
58Wang, Yujie
59Weeke, Peter E
60Wu, Hongsheng
61Yang, Wei
62Zeng, Donglin
63Witte, Daniel R
64Weir, Bruce S
65Wareham, Nicholas J
66Vestergaard, Henrik
67Turner, Stephen T
68Torp-Pedersen, Christian
69Stergiakouli, Evie
70Ikram, M. Arfan
71Franco, Oscar H
72Ridker, Paul M
73Pedersen, Oluf
74Nohr, Ellen A
75Newman, Anne B
76Linneberg, Allan
77Langenberg, Claudia
78Kilpeläinen, Tuomas O
79Kardia, Sharon L.R
80Jørgensen, Torben
81Homuth, Georg
82Hansen, Torben
83Goodarzi, Mark O
84Deary, Ian J
85Christensen, Cramer
86Chen, Yii-Der Ida
87Bonnelykke, Klaus
88Rodriguez, Santiago
89Davies, Gail
90Horta, Bernardo L
91Thyagarajan, Bharat
92Grarup, Niels
93Guo, Xiuqing
94Tiwari, Hemant K
95Malik, Afshan N
96Scott, Robert A
97de Andrade, Mariza
98Province, Michael A
99Rotter, Jerome I
general
0Elsevier Inc
1Elsevier B.V
2Elsevier
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creationdate20190103
titleAssociations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits
authorKraja, Aldi T ; Fetterman, Jessica L ; Graff, Mariaelisa ; Have, Christian Theil ; Yanek, Lisa R ; Arking, Dan E ; Chasman, Daniel I ; Young, Kristin ; Ligthart, Symen ; Hill, W. David ; Weiss, Stefan ; Luan, Jian’an ; Giulianini, Franco ; Hartwig, Fernando P ; Lin, Shiow J ; Wang, Lihua ; Richardson, Tom G ; Ghanbari, Mohsen ; Wojczynski, Mary K ; Lee, Wen-Jane ; Armasu, Sebastian M ; Barve, Ruteja A ; Ryan, Kathleen A ; An, Ping ; Bielinski, Suzette J ; Bowden, Donald W ; Broeckel, Ulrich ; Chu, Audrey Y ; Corley, Janie ; Cox, Simon R ; Uitterlinden, Andre G ; Rivadeneira, Fernando ; Daw, E. Warwick ; de las Fuentes, Lisa ; Gao, He ; Ahluwalia, Tarunveer S ; de Mutsert, Renée ; Emery, Leslie S ; Erzurumluoglu, A. Mesut ; Perry, James A ; Fu, Mao ; Forouhi, Nita G ; Gu, Zhenglong ; Harris, Sarah E ; Irvin, Marguerite R ; Jonsson, Anna E ; Kerrison, Nicola D ; Larson, Nicholas B ; Lin, Keng-Hung ; Mathias, Rasika A ; Lee, Joseph H ; Nauck, Matthias ; Pankow, James ; Patki, Amit ; Qi, Qibin ; Sofer, Tamar ; Starr, John M ; de Haan, Hugoline G ; Wang, Yujie ; Weeke, Peter E ; Wu, Hongsheng ; Yang, Wei ; Zeng, Donglin ; Witte, Daniel R ; Weir, Bruce S ; Wareham, Nicholas J ; Vestergaard, Henrik ; Turner, Stephen T ; Torp-Pedersen, Christian ; Stergiakouli, Evie ; Ikram, M. Arfan ; Franco, Oscar H ; Ridker, Paul M ; Pedersen, Oluf ; Nohr, Ellen A ; Newman, Anne B ; Linneberg, Allan ; Langenberg, Claudia ; Kilpeläinen, Tuomas O ; Kardia, Sharon L.R ; Jørgensen, Torben ; Homuth, Georg ; Hansen, Torben ; Goodarzi, Mark O ; Deary, Ian J ; Christensen, Cramer ; Chen, Yii-Der Ida ; Bonnelykke, Klaus ; Rodriguez, Santiago ; Davies, Gail ; Horta, Bernardo L ; Thyagarajan, Bharat ; Grarup, Niels ; Guo, Xiuqing ; Tiwari, Hemant K ; Malik, Afshan N ; Scott, Robert A ; de Andrade, Mariza ; Province, Michael A ; Rotter, Jerome I
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1546t-756e4d4ae331fa1f12ccd4a509e4c14dc86ebd9821d9d66a633d3ad74f04f41a3
rsrctypearticles
prefilterarticles
languageeng
creationdate2019
topic
0Adipocytes - metabolism
1BMI
2Body Mass Index
3Cardiovascular Diseases - genetics
4Cardiovascular Diseases - metabolism
5Cohort Studies
6Diabetes Mellitus - genetics
7Diabetes Mellitus - metabolism
8DNA, Mitochondrial - genetics
9Genes, Mitochondrial - genetics
10Genetic aspects
11Genetic Variation - genetics
12Genome-wide association studies
13glucose
14Glucose - metabolism
15Glycated Hemoglobin A - metabolism
16HbA1c
17HOMA-B
18HOMA-IR
19Humans
20insulin
21Insulin - metabolism
22Metabolic diseases
23Metabolism - genetics
24mitochondria
25Mitochondria - genetics
26Mitochondria - metabolism
27Mitochondrial DNA
28MT-nDNA candidate genes
29mtDNA
30Physiological aspects
31Quantitative Trait Loci
32Risk factors
33Usage
34Waist-Hip Ratio
35waist-to-hip ratio
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Kraja, Aldi T
1Fetterman, Jessica L
2Graff, Mariaelisa
3Have, Christian Theil
4Yanek, Lisa R
5Arking, Dan E
6Chasman, Daniel I
7Young, Kristin
8Ligthart, Symen
9Hill, W. David
10Weiss, Stefan
11Luan, Jian’an
12Giulianini, Franco
13Hartwig, Fernando P
14Lin, Shiow J
15Wang, Lihua
16Richardson, Tom G
17Ghanbari, Mohsen
18Wojczynski, Mary K
19Lee, Wen-Jane
20Armasu, Sebastian M
21Barve, Ruteja A
22Ryan, Kathleen A
23An, Ping
24Bielinski, Suzette J
25Bowden, Donald W
26Broeckel, Ulrich
27Chu, Audrey Y
28Corley, Janie
29Cox, Simon R
30Uitterlinden, Andre G
31Rivadeneira, Fernando
32Daw, E. Warwick
33de las Fuentes, Lisa
34Gao, He
35Ahluwalia, Tarunveer S
36de Mutsert, Renée
37Emery, Leslie S
38Erzurumluoglu, A. Mesut
39Perry, James A
40Fu, Mao
41Forouhi, Nita G
42Gu, Zhenglong
43Harris, Sarah E
44Irvin, Marguerite R
45Jonsson, Anna E
46Kerrison, Nicola D
47Larson, Nicholas B
48Lin, Keng-Hung
49Mathias, Rasika A
50Lee, Joseph H
51Nauck, Matthias
52Pankow, James
53Patki, Amit
54Qi, Qibin
55Sofer, Tamar
56Starr, John M
57de Haan, Hugoline G
58Wang, Yujie
59Weeke, Peter E
60Wu, Hongsheng
61Yang, Wei
62Zeng, Donglin
63Witte, Daniel R
64Weir, Bruce S
65Wareham, Nicholas J
66Vestergaard, Henrik
67Turner, Stephen T
68Torp-Pedersen, Christian
69Stergiakouli, Evie
70Ikram, M. Arfan
71Franco, Oscar H
72Ridker, Paul M
73Pedersen, Oluf
74Nohr, Ellen A
75Newman, Anne B
76Linneberg, Allan
77Langenberg, Claudia
78Kilpeläinen, Tuomas O
79Kardia, Sharon L.R
80Jørgensen, Torben
81Homuth, Georg
82Hansen, Torben
83Goodarzi, Mark O
84Deary, Ian J
85Christensen, Cramer
86Chen, Yii-Der Ida
87Bonnelykke, Klaus
88Rodriguez, Santiago
89Davies, Gail
90Horta, Bernardo L
91Thyagarajan, Bharat
92Grarup, Niels
93Guo, Xiuqing
94Tiwari, Hemant K
95Malik, Afshan N
96Scott, Robert A
97de Andrade, Mariza
98Province, Michael A
99Rotter, Jerome I
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)
13MEDLINE - Academic
14PubMed Central (Full Participant titles)
jtitleAmerican journal of human genetics
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Kraja, Aldi T
1Fetterman, Jessica L
2Graff, Mariaelisa
3Have, Christian Theil
4Yanek, Lisa R
5Arking, Dan E
6Chasman, Daniel I
7Young, Kristin
8Ligthart, Symen
9Hill, W. David
10Weiss, Stefan
11Luan, Jian’an
12Giulianini, Franco
13Hartwig, Fernando P
14Lin, Shiow J
15Wang, Lihua
16Richardson, Tom G
17Ghanbari, Mohsen
18Wojczynski, Mary K
19Lee, Wen-Jane
20Armasu, Sebastian M
21Barve, Ruteja A
22Ryan, Kathleen A
23An, Ping
24Bielinski, Suzette J
25Bowden, Donald W
26Broeckel, Ulrich
27Chu, Audrey Y
28Corley, Janie
29Cox, Simon R
30Uitterlinden, Andre G
31Rivadeneira, Fernando
32Daw, E. Warwick
33de las Fuentes, Lisa
34Gao, He
35Ahluwalia, Tarunveer S
36de Mutsert, Renée
37Emery, Leslie S
38Erzurumluoglu, A. Mesut
39Perry, James A
40Fu, Mao
41Forouhi, Nita G
42Gu, Zhenglong
43Harris, Sarah E
44Irvin, Marguerite R
45Jonsson, Anna E
46Kerrison, Nicola D
47Larson, Nicholas B
48Lin, Keng-Hung
49Mathias, Rasika A
50Lee, Joseph H
51Nauck, Matthias
52Pankow, James
53Patki, Amit
54Qi, Qibin
55Sofer, Tamar
56Starr, John M
57de Haan, Hugoline G
58Wang, Yujie
59Weeke, Peter E
60Wu, Hongsheng
61Yang, Wei
62Zeng, Donglin
63Witte, Daniel R
64Weir, Bruce S
65Wareham, Nicholas J
66Vestergaard, Henrik
67Turner, Stephen T
68Torp-Pedersen, Christian
69Stergiakouli, Evie
70Ikram, M. Arfan
71Franco, Oscar H
72Ridker, Paul M
73Pedersen, Oluf
74Nohr, Ellen A
75Newman, Anne B
76Linneberg, Allan
77Langenberg, Claudia
78Kilpeläinen, Tuomas O
79Kardia, Sharon L.R
80Jørgensen, Torben
81Homuth, Georg
82Hansen, Torben
83Goodarzi, Mark O
84Deary, Ian J
85Christensen, Cramer
86Chen, Yii-Der Ida
87Bonnelykke, Klaus
88Rodriguez, Santiago
89Davies, Gail
90Horta, Bernardo L
91Thyagarajan, Bharat
92Grarup, Niels
93Guo, Xiuqing
94Tiwari, Hemant K
95Malik, Afshan N
96Scott, Robert A
97de Andrade, Mariza
98Province, Michael A
99Rotter, Jerome I
formatjournal
genrearticle
ristypeJOUR
atitleAssociations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits
jtitleAmerican journal of human genetics
addtitleAm J Hum Genet
date2019-01-03
risdate2019
volume104
issue1
spage112
epage138
pages112-138
issn0002-9297
eissn1537-6605
notes
0These authors contributed equally to this work
1Co-senior author
abstractMitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E−04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E−03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia’s genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E−06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.
copUnited States
pubElsevier Inc
pmid30595373
doi10.1016/j.ajhg.2018.12.001
oafree_for_read