Loading…
Gene–Environment Interactions for Parkinson's Disease
Objective Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD‐related genetic and...
Saved in:
| Published in: | Annals of neurology 2024-04, Vol.95 (4), p.677-687 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c3882-46459f38d20473bf9155ad139d9a2da6652e6fe5dfb10181fce5a9ac034555a3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c3882-46459f38d20473bf9155ad139d9a2da6652e6fe5dfb10181fce5a9ac034555a3 |
| container_end_page | 687 |
| container_issue | 4 |
| container_start_page | 677 |
| container_title | Annals of neurology |
| container_volume | 95 |
| creator | Reynoso, Alexandra Torricelli, Roberta Jacobs, Benjamin Meir Shi, Jingchunzi Aslibekyan, Stella Norcliffe‐Kaufmann, Lucy Noyce, Alastair J Heilbron, Karl |
| description | Objective
Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD‐related genetic and environmental exposures in the 23andMe, Inc. research dataset.
Methods
Using a validated PD polygenic risk score and common PD‐associated variants in the GBA gene, we explored interactions between genetic susceptibility factors and 7 lifestyle and environmental factors: body mass index (BMI), type 2 diabetes (T2D), tobacco use, caffeine consumption, pesticide exposure, head injury, and physical activity (PA).
Results
We observed that T2D, as well as higher BMI, caffeine consumption, and tobacco use, were associated with lower odds of PD, whereas head injury, pesticide exposure, GBA carrier status, and PD polygenic risk score were associated with higher odds. No significant association was observed between PA and PD. In interaction analyses, we found statistical evidence for an interaction between polygenic risk of PD and the following environmental/lifestyle factors: T2D (p = 6.502 × 10−8), PA (p = 8.745 × 10−5), BMI (p = 4.314 × 10−4), and tobacco use (p = 2.236 × 10−3). Although BMI and tobacco use were associated with lower odds of PD regardless of the extent of individual genetic liability, the direction of the relationship between odds of PD and T2D, as well as PD and PA, varied depending on polygenic risk score.
Interpretation
We provide preliminary evidence that associations between some environmental and lifestyle factors and PD may be modified by genotype. ANN NEUROL 2024;95:677–687 |
| doi_str_mv | 10.1002/ana.26852 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2904153966</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2904153966</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3882-46459f38d20473bf9155ad139d9a2da6652e6fe5dfb10181fce5a9ac034555a3</originalsourceid><addsrcrecordid>eNp10D9OwzAchmELgWgpDFwARWIAhrT-33isSimVEDB0t9zEllISu9gJqBt34IacBEMKAxKTl0effn4BOEVwiCDEI2XVEPOM4T3QR4ygNMNU7IM-JJymDBHaA0chrCGEgiN4CHokQ4gQzPtgPNdWf7y9z-xL6Z2ttW2ShW20V3lTOhsS43zyqPxTaYOzFyG5LoNWQR-DA6OqoE927wAsb2bL6W169zBfTCd3aU6yDKeUUyYMyQoM6ZisjECMqQIRUQiFC8U5w5obzQqzQhBlyOSaKaFySCiLkgzAZTe78e651aGRdRlyXVXKatcGiQWk8ceC80jP_9C1a72Nx0kCo4iO0qiuOpV7F4LXRm58WSu_lQjKr5gyxpTfMaM92y22q1oXv_KnXgSjDryWld7-vyQn95Nu8hMdY3yo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3039641544</pqid></control><display><type>article</type><title>Gene–Environment Interactions for Parkinson's Disease</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>Reynoso, Alexandra ; Torricelli, Roberta ; Jacobs, Benjamin Meir ; Shi, Jingchunzi ; Aslibekyan, Stella ; Norcliffe‐Kaufmann, Lucy ; Noyce, Alastair J ; Heilbron, Karl</creator><creatorcontrib>Reynoso, Alexandra ; Torricelli, Roberta ; Jacobs, Benjamin Meir ; Shi, Jingchunzi ; Aslibekyan, Stella ; Norcliffe‐Kaufmann, Lucy ; Noyce, Alastair J ; Heilbron, Karl</creatorcontrib><description>Objective
Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD‐related genetic and environmental exposures in the 23andMe, Inc. research dataset.
Methods
Using a validated PD polygenic risk score and common PD‐associated variants in the GBA gene, we explored interactions between genetic susceptibility factors and 7 lifestyle and environmental factors: body mass index (BMI), type 2 diabetes (T2D), tobacco use, caffeine consumption, pesticide exposure, head injury, and physical activity (PA).
Results
We observed that T2D, as well as higher BMI, caffeine consumption, and tobacco use, were associated with lower odds of PD, whereas head injury, pesticide exposure, GBA carrier status, and PD polygenic risk score were associated with higher odds. No significant association was observed between PA and PD. In interaction analyses, we found statistical evidence for an interaction between polygenic risk of PD and the following environmental/lifestyle factors: T2D (p = 6.502 × 10−8), PA (p = 8.745 × 10−5), BMI (p = 4.314 × 10−4), and tobacco use (p = 2.236 × 10−3). Although BMI and tobacco use were associated with lower odds of PD regardless of the extent of individual genetic liability, the direction of the relationship between odds of PD and T2D, as well as PD and PA, varied depending on polygenic risk score.
Interpretation
We provide preliminary evidence that associations between some environmental and lifestyle factors and PD may be modified by genotype. ANN NEUROL 2024;95:677–687</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.26852</identifier><identifier>PMID: 38113326</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Body mass index ; Body size ; Caffeine ; Diabetes mellitus (non-insulin dependent) ; Environmental factors ; Genotypes ; Glucosylceramidase ; Head injuries ; Liability ; Lifestyles ; Movement disorders ; Neurodegenerative diseases ; Parkinson's disease ; Pesticides ; Physical activity ; Risk ; Statistics ; Susceptibility ; Tobacco</subject><ispartof>Annals of neurology, 2024-04, Vol.95 (4), p.677-687</ispartof><rights>2023 The Authors. published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3882-46459f38d20473bf9155ad139d9a2da6652e6fe5dfb10181fce5a9ac034555a3</citedby><cites>FETCH-LOGICAL-c3882-46459f38d20473bf9155ad139d9a2da6652e6fe5dfb10181fce5a9ac034555a3</cites><orcidid>0009-0004-6124-2879 ; 0000-0003-3027-5497 ; 0000-0003-4776-1723 ; 0000-0002-9194-8344 ; 0000-0002-6023-6010</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38113326$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reynoso, Alexandra</creatorcontrib><creatorcontrib>Torricelli, Roberta</creatorcontrib><creatorcontrib>Jacobs, Benjamin Meir</creatorcontrib><creatorcontrib>Shi, Jingchunzi</creatorcontrib><creatorcontrib>Aslibekyan, Stella</creatorcontrib><creatorcontrib>Norcliffe‐Kaufmann, Lucy</creatorcontrib><creatorcontrib>Noyce, Alastair J</creatorcontrib><creatorcontrib>Heilbron, Karl</creatorcontrib><title>Gene–Environment Interactions for Parkinson's Disease</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD‐related genetic and environmental exposures in the 23andMe, Inc. research dataset.
Methods
Using a validated PD polygenic risk score and common PD‐associated variants in the GBA gene, we explored interactions between genetic susceptibility factors and 7 lifestyle and environmental factors: body mass index (BMI), type 2 diabetes (T2D), tobacco use, caffeine consumption, pesticide exposure, head injury, and physical activity (PA).
Results
We observed that T2D, as well as higher BMI, caffeine consumption, and tobacco use, were associated with lower odds of PD, whereas head injury, pesticide exposure, GBA carrier status, and PD polygenic risk score were associated with higher odds. No significant association was observed between PA and PD. In interaction analyses, we found statistical evidence for an interaction between polygenic risk of PD and the following environmental/lifestyle factors: T2D (p = 6.502 × 10−8), PA (p = 8.745 × 10−5), BMI (p = 4.314 × 10−4), and tobacco use (p = 2.236 × 10−3). Although BMI and tobacco use were associated with lower odds of PD regardless of the extent of individual genetic liability, the direction of the relationship between odds of PD and T2D, as well as PD and PA, varied depending on polygenic risk score.
Interpretation
We provide preliminary evidence that associations between some environmental and lifestyle factors and PD may be modified by genotype. ANN NEUROL 2024;95:677–687</description><subject>Body mass index</subject><subject>Body size</subject><subject>Caffeine</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Environmental factors</subject><subject>Genotypes</subject><subject>Glucosylceramidase</subject><subject>Head injuries</subject><subject>Liability</subject><subject>Lifestyles</subject><subject>Movement disorders</subject><subject>Neurodegenerative diseases</subject><subject>Parkinson's disease</subject><subject>Pesticides</subject><subject>Physical activity</subject><subject>Risk</subject><subject>Statistics</subject><subject>Susceptibility</subject><subject>Tobacco</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp10D9OwzAchmELgWgpDFwARWIAhrT-33isSimVEDB0t9zEllISu9gJqBt34IacBEMKAxKTl0effn4BOEVwiCDEI2XVEPOM4T3QR4ygNMNU7IM-JJymDBHaA0chrCGEgiN4CHokQ4gQzPtgPNdWf7y9z-xL6Z2ttW2ShW20V3lTOhsS43zyqPxTaYOzFyG5LoNWQR-DA6OqoE927wAsb2bL6W169zBfTCd3aU6yDKeUUyYMyQoM6ZisjECMqQIRUQiFC8U5w5obzQqzQhBlyOSaKaFySCiLkgzAZTe78e651aGRdRlyXVXKatcGiQWk8ceC80jP_9C1a72Nx0kCo4iO0qiuOpV7F4LXRm58WSu_lQjKr5gyxpTfMaM92y22q1oXv_KnXgSjDryWld7-vyQn95Nu8hMdY3yo</recordid><startdate>202404</startdate><enddate>202404</enddate><creator>Reynoso, Alexandra</creator><creator>Torricelli, Roberta</creator><creator>Jacobs, Benjamin Meir</creator><creator>Shi, Jingchunzi</creator><creator>Aslibekyan, Stella</creator><creator>Norcliffe‐Kaufmann, Lucy</creator><creator>Noyce, Alastair J</creator><creator>Heilbron, Karl</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0009-0004-6124-2879</orcidid><orcidid>https://orcid.org/0000-0003-3027-5497</orcidid><orcidid>https://orcid.org/0000-0003-4776-1723</orcidid><orcidid>https://orcid.org/0000-0002-9194-8344</orcidid><orcidid>https://orcid.org/0000-0002-6023-6010</orcidid></search><sort><creationdate>202404</creationdate><title>Gene–Environment Interactions for Parkinson's Disease</title><author>Reynoso, Alexandra ; Torricelli, Roberta ; Jacobs, Benjamin Meir ; Shi, Jingchunzi ; Aslibekyan, Stella ; Norcliffe‐Kaufmann, Lucy ; Noyce, Alastair J ; Heilbron, Karl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3882-46459f38d20473bf9155ad139d9a2da6652e6fe5dfb10181fce5a9ac034555a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Body mass index</topic><topic>Body size</topic><topic>Caffeine</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Environmental factors</topic><topic>Genotypes</topic><topic>Glucosylceramidase</topic><topic>Head injuries</topic><topic>Liability</topic><topic>Lifestyles</topic><topic>Movement disorders</topic><topic>Neurodegenerative diseases</topic><topic>Parkinson's disease</topic><topic>Pesticides</topic><topic>Physical activity</topic><topic>Risk</topic><topic>Statistics</topic><topic>Susceptibility</topic><topic>Tobacco</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reynoso, Alexandra</creatorcontrib><creatorcontrib>Torricelli, Roberta</creatorcontrib><creatorcontrib>Jacobs, Benjamin Meir</creatorcontrib><creatorcontrib>Shi, Jingchunzi</creatorcontrib><creatorcontrib>Aslibekyan, Stella</creatorcontrib><creatorcontrib>Norcliffe‐Kaufmann, Lucy</creatorcontrib><creatorcontrib>Noyce, Alastair J</creatorcontrib><creatorcontrib>Heilbron, Karl</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reynoso, Alexandra</au><au>Torricelli, Roberta</au><au>Jacobs, Benjamin Meir</au><au>Shi, Jingchunzi</au><au>Aslibekyan, Stella</au><au>Norcliffe‐Kaufmann, Lucy</au><au>Noyce, Alastair J</au><au>Heilbron, Karl</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene–Environment Interactions for Parkinson's Disease</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2024-04</date><risdate>2024</risdate><volume>95</volume><issue>4</issue><spage>677</spage><epage>687</epage><pages>677-687</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><abstract>Objective
Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD‐related genetic and environmental exposures in the 23andMe, Inc. research dataset.
Methods
Using a validated PD polygenic risk score and common PD‐associated variants in the GBA gene, we explored interactions between genetic susceptibility factors and 7 lifestyle and environmental factors: body mass index (BMI), type 2 diabetes (T2D), tobacco use, caffeine consumption, pesticide exposure, head injury, and physical activity (PA).
Results
We observed that T2D, as well as higher BMI, caffeine consumption, and tobacco use, were associated with lower odds of PD, whereas head injury, pesticide exposure, GBA carrier status, and PD polygenic risk score were associated with higher odds. No significant association was observed between PA and PD. In interaction analyses, we found statistical evidence for an interaction between polygenic risk of PD and the following environmental/lifestyle factors: T2D (p = 6.502 × 10−8), PA (p = 8.745 × 10−5), BMI (p = 4.314 × 10−4), and tobacco use (p = 2.236 × 10−3). Although BMI and tobacco use were associated with lower odds of PD regardless of the extent of individual genetic liability, the direction of the relationship between odds of PD and T2D, as well as PD and PA, varied depending on polygenic risk score.
Interpretation
We provide preliminary evidence that associations between some environmental and lifestyle factors and PD may be modified by genotype. ANN NEUROL 2024;95:677–687</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>38113326</pmid><doi>10.1002/ana.26852</doi><tpages>11</tpages><orcidid>https://orcid.org/0009-0004-6124-2879</orcidid><orcidid>https://orcid.org/0000-0003-3027-5497</orcidid><orcidid>https://orcid.org/0000-0003-4776-1723</orcidid><orcidid>https://orcid.org/0000-0002-9194-8344</orcidid><orcidid>https://orcid.org/0000-0002-6023-6010</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0364-5134 |
| ispartof | Annals of neurology, 2024-04, Vol.95 (4), p.677-687 |
| issn | 0364-5134 1531-8249 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2904153966 |
| source | Wiley-Blackwell Read & Publish Collection |
| subjects | Body mass index Body size Caffeine Diabetes mellitus (non-insulin dependent) Environmental factors Genotypes Glucosylceramidase Head injuries Liability Lifestyles Movement disorders Neurodegenerative diseases Parkinson's disease Pesticides Physical activity Risk Statistics Susceptibility Tobacco |
| title | Gene–Environment Interactions for Parkinson's Disease |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T03%3A40%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Gene%E2%80%93Environment%20Interactions%20for%20Parkinson's%20Disease&rft.jtitle=Annals%20of%20neurology&rft.au=Reynoso,%20Alexandra&rft.date=2024-04&rft.volume=95&rft.issue=4&rft.spage=677&rft.epage=687&rft.pages=677-687&rft.issn=0364-5134&rft.eissn=1531-8249&rft_id=info:doi/10.1002/ana.26852&rft_dat=%3Cproquest_cross%3E2904153966%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3882-46459f38d20473bf9155ad139d9a2da6652e6fe5dfb10181fce5a9ac034555a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3039641544&rft_id=info:pmid/38113326&rfr_iscdi=true |