Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism

Theresa Lüth; Carolin Gabbert; Sebastian Koch; Inke R König; Amke Caliebe; Björn-Hergen Laabs; Faycel Hentati; Samia Ben Sassi; Rim Amouri; Malte Spielmann; Christine Klein; Anne Grünewald; Matthew J Farrer; Joanne Trinh

doi:10.1002/mds.29563

Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism

Theresa Lüth, Carolin Gabbert, Sebastian Koch, Inke R König, Amke Caliebe, Björn-Hergen Laabs, Faycel Hentati, Samia Ben Sassi, Rim Amouri, Malte Spielmann, Christine Klein, Anne Grünewald, Matthew J Farrer, Joanne Trinh

Abstract

BACKGROUND: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk.

OBJECTIVE: To investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic PD (iPD).

METHODS: We included N = 486 patients with LRRK2-PD and N = 9259 with iPD from the Accelerating Medicines Partnership® Parkinson's Disease Knowledge Platform (AMP-PD), Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD-RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO.

RESULTS: Our derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10-8 ). We observed that higher MGS was significantly associated with earlier AAO in LRRK2-PD (P = 0.047, β = -1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, β = 0.22). There was a correlation between MGS and AAO in LRRK2-PD patients of European descent (P = 0.049, r = -0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = -0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, β = -5.65) in LRRK2-PD and with tobacco use (P = 0.010, β = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non-smokers.

CONCLUSIONS: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Originalsprache	Englisch
Zeitschrift	Movement disorders : official journal of the Movement Disorder Society
Jahrgang	38
Ausgabenummer	10
Seiten (von - bis)	1837-1849
Seitenumfang	13
ISSN	0885-3185
DOIs	https://doi.org/10.1002/mds.29563
Publikationsstatus	Veröffentlicht - 10.2023

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10.1002/mds.29563

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Lüth, T., Gabbert, C., Koch, S., König, I. R., Caliebe, A., Laabs, B-H., Hentati, F., Sassi, S. B., Amouri, R., Spielmann, M., Klein, C., Grünewald, A., Farrer, M. J., & Trinh, J. (2023). Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism. Movement disorders : official journal of the Movement Disorder Society, 38(10), 1837-1849. https://doi.org/10.1002/mds.29563

@article{4255a0956a394b2a9bc87b50ec313f1d,

title = "Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism",

abstract = "BACKGROUND: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk.OBJECTIVE: To investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic PD (iPD).METHODS: We included N = 486 patients with LRRK2-PD and N = 9259 with iPD from the Accelerating Medicines Partnership{\textregistered} Parkinson's Disease Knowledge Platform (AMP-PD), Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD-RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO.RESULTS: Our derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10-8 ). We observed that higher MGS was significantly associated with earlier AAO in LRRK2-PD (P = 0.047, β = -1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, β = 0.22). There was a correlation between MGS and AAO in LRRK2-PD patients of European descent (P = 0.049, r = -0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = -0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, β = -5.65) in LRRK2-PD and with tobacco use (P = 0.010, β = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non-smokers.CONCLUSIONS: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD. {\textcopyright} 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

author = "Theresa L{\"u}th and Carolin Gabbert and Sebastian Koch and K{\"o}nig, {Inke R} and Amke Caliebe and Bj{\"o}rn-Hergen Laabs and Faycel Hentati and Sassi, {Samia Ben} and Rim Amouri and Malte Spielmann and Christine Klein and Anne Gr{\"u}newald and Farrer, {Matthew J} and Joanne Trinh",

note = "{\textcopyright} 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

year = "2023",

month = oct,

doi = "10.1002/mds.29563",

language = "English",

volume = "38",

pages = "1837--1849",

journal = "Movement disorders : official journal of the Movement Disorder Society",

issn = "0885-3185",

number = "10",

}

Lüth, T , Gabbert, C, Koch, S, König, IR, Caliebe, A, Laabs, B-H, Hentati, F, Sassi, SB, Amouri, R, Spielmann, M , Klein, C, Grünewald, A, Farrer, MJ & Trinh, J 2023, 'Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism', Movement disorders : official journal of the Movement Disorder Society, Jg. 38, Nr. 10, S. 1837-1849. https://doi.org/10.1002/mds.29563

Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism. / Lüth, Theresa ; Gabbert, Carolin; Koch, Sebastian et al.
in: Movement disorders : official journal of the Movement Disorder Society, Jahrgang 38, Nr. 10, 10.2023, S. 1837-1849.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism

AU - Lüth, Theresa

AU - Gabbert, Carolin

AU - Koch, Sebastian

AU - König, Inke R

AU - Caliebe, Amke

AU - Laabs, Björn-Hergen

AU - Hentati, Faycel

AU - Sassi, Samia Ben

AU - Amouri, Rim

AU - Spielmann, Malte

AU - Klein, Christine

AU - Grünewald, Anne

AU - Farrer, Matthew J

AU - Trinh, Joanne

PY - 2023/10

Y1 - 2023/10

N2 - BACKGROUND: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk.OBJECTIVE: To investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic PD (iPD).METHODS: We included N = 486 patients with LRRK2-PD and N = 9259 with iPD from the Accelerating Medicines Partnership® Parkinson's Disease Knowledge Platform (AMP-PD), Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD-RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO.RESULTS: Our derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10-8 ). We observed that higher MGS was significantly associated with earlier AAO in LRRK2-PD (P = 0.047, β = -1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, β = 0.22). There was a correlation between MGS and AAO in LRRK2-PD patients of European descent (P = 0.049, r = -0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = -0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, β = -5.65) in LRRK2-PD and with tobacco use (P = 0.010, β = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non-smokers.CONCLUSIONS: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

AB - BACKGROUND: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk.OBJECTIVE: To investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic PD (iPD).METHODS: We included N = 486 patients with LRRK2-PD and N = 9259 with iPD from the Accelerating Medicines Partnership® Parkinson's Disease Knowledge Platform (AMP-PD), Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD-RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO.RESULTS: Our derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10-8 ). We observed that higher MGS was significantly associated with earlier AAO in LRRK2-PD (P = 0.047, β = -1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, β = 0.22). There was a correlation between MGS and AAO in LRRK2-PD patients of European descent (P = 0.049, r = -0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = -0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, β = -5.65) in LRRK2-PD and with tobacco use (P = 0.010, β = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non-smokers.CONCLUSIONS: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

U2 - 10.1002/mds.29563

DO - 10.1002/mds.29563

M3 - Journal articles

C2 - 37482924

SN - 0885-3185

VL - 38

SP - 1837

EP - 1849

JO - Movement disorders : official journal of the Movement Disorder Society

JF - Movement disorders : official journal of the Movement Disorder Society

IS - 10

ER -

Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism

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