Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids

Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK B...
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Autor*in:	Davyson, Eleanor [verfasserIn] Shen, Xueyi [verfasserIn] Gadd, Danni A. [verfasserIn] Bernabeu, Elena [verfasserIn] Hillary, Robert F. [verfasserIn] McCartney, Daniel L. [verfasserIn] Adams, Mark [verfasserIn] Marioni, Riccardo [verfasserIn] McIntosh, Andrew M. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Colocalization Depression Fatty acids Mendelian randomization Metabolome Multiomics

Übergeordnetes Werk:	Enthalten in: Biological psychiatry - Amsterdam [u.a.] : Elsevier Science, 1985, 94, Seite 630-639
Übergeordnetes Werk:	volume:94 ; pages:630-639

DOI / URN:	10.1016/j.biopsych.2023.01.027

Katalog-ID:	ELV064396835

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100	1		\|a Davyson, Eleanor \|e verfasserin \|0 (orcid)0000-0002-7313-0530 \|4 aut
245	1	0	\|a Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids
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337			\|a Computermedien \|b c \|2 rdamedia
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520			\|a Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD.
650		4	\|a Colocalization
650		4	\|a Depression
650		4	\|a Fatty acids
650		4	\|a Mendelian randomization
650		4	\|a Metabolome
650		4	\|a Multiomics
700	1		\|a Shen, Xueyi \|e verfasserin \|4 aut
700	1		\|a Gadd, Danni A. \|e verfasserin \|4 aut
700	1		\|a Bernabeu, Elena \|e verfasserin \|4 aut
700	1		\|a Hillary, Robert F. \|e verfasserin \|4 aut
700	1		\|a McCartney, Daniel L. \|e verfasserin \|4 aut
700	1		\|a Adams, Mark \|e verfasserin \|4 aut
700	1		\|a Marioni, Riccardo \|e verfasserin \|4 aut
700	1		\|a McIntosh, Andrew M. \|e verfasserin \|0 (orcid)0000-0002-0198-4588 \|4 aut
773	0	8	\|i Enthalten in \|t Biological psychiatry \|d Amsterdam [u.a.] : Elsevier Science, 1985 \|g 94, Seite 630-639 \|h Online-Ressource \|w (DE-627)306654296 \|w (DE-600)1499907-9 \|w (DE-576)115780807 \|x 1873-2402 \|7 nnns
773	1	8	\|g volume:94 \|g pages:630-639
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936	b	k	\|a 42.00 \|j Biologie: Allgemeines \|q VZ
936	b	k	\|a 44.91 \|j Psychiatrie \|j Psychopathologie \|q VZ
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allfields	10.1016/j.biopsych.2023.01.027 doi (DE-627)ELV064396835 (ELSEVIER)S0006-3223(23)00055-0 DE-627 ger DE-627 rda eng 570 610 VZ LING DE-30 fid 42.00 bkl 44.91 bkl Davyson, Eleanor verfasserin (orcid)0000-0002-7313-0530 aut Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD. Colocalization Depression Fatty acids Mendelian randomization Metabolome Multiomics Shen, Xueyi verfasserin aut Gadd, Danni A. verfasserin aut Bernabeu, Elena verfasserin aut Hillary, Robert F. verfasserin aut McCartney, Daniel L. verfasserin aut Adams, Mark verfasserin aut Marioni, Riccardo verfasserin aut McIntosh, Andrew M. verfasserin (orcid)0000-0002-0198-4588 aut Enthalten in Biological psychiatry Amsterdam [u.a.] : Elsevier Science, 1985 94, Seite 630-639 Online-Ressource (DE-627)306654296 (DE-600)1499907-9 (DE-576)115780807 1873-2402 nnns volume:94 pages:630-639 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-LING SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.00 Biologie: Allgemeines VZ 44.91 Psychiatrie Psychopathologie VZ AR 94 630-639
spelling	10.1016/j.biopsych.2023.01.027 doi (DE-627)ELV064396835 (ELSEVIER)S0006-3223(23)00055-0 DE-627 ger DE-627 rda eng 570 610 VZ LING DE-30 fid 42.00 bkl 44.91 bkl Davyson, Eleanor verfasserin (orcid)0000-0002-7313-0530 aut Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD. Colocalization Depression Fatty acids Mendelian randomization Metabolome Multiomics Shen, Xueyi verfasserin aut Gadd, Danni A. verfasserin aut Bernabeu, Elena verfasserin aut Hillary, Robert F. verfasserin aut McCartney, Daniel L. verfasserin aut Adams, Mark verfasserin aut Marioni, Riccardo verfasserin aut McIntosh, Andrew M. verfasserin (orcid)0000-0002-0198-4588 aut Enthalten in Biological psychiatry Amsterdam [u.a.] : Elsevier Science, 1985 94, Seite 630-639 Online-Ressource (DE-627)306654296 (DE-600)1499907-9 (DE-576)115780807 1873-2402 nnns volume:94 pages:630-639 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-LING SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.00 Biologie: Allgemeines VZ 44.91 Psychiatrie Psychopathologie VZ AR 94 630-639
allfields_unstemmed	10.1016/j.biopsych.2023.01.027 doi (DE-627)ELV064396835 (ELSEVIER)S0006-3223(23)00055-0 DE-627 ger DE-627 rda eng 570 610 VZ LING DE-30 fid 42.00 bkl 44.91 bkl Davyson, Eleanor verfasserin (orcid)0000-0002-7313-0530 aut Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD. Colocalization Depression Fatty acids Mendelian randomization Metabolome Multiomics Shen, Xueyi verfasserin aut Gadd, Danni A. verfasserin aut Bernabeu, Elena verfasserin aut Hillary, Robert F. verfasserin aut McCartney, Daniel L. verfasserin aut Adams, Mark verfasserin aut Marioni, Riccardo verfasserin aut McIntosh, Andrew M. verfasserin (orcid)0000-0002-0198-4588 aut Enthalten in Biological psychiatry Amsterdam [u.a.] : Elsevier Science, 1985 94, Seite 630-639 Online-Ressource (DE-627)306654296 (DE-600)1499907-9 (DE-576)115780807 1873-2402 nnns volume:94 pages:630-639 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-LING SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.00 Biologie: Allgemeines VZ 44.91 Psychiatrie Psychopathologie VZ AR 94 630-639
allfieldsGer	10.1016/j.biopsych.2023.01.027 doi (DE-627)ELV064396835 (ELSEVIER)S0006-3223(23)00055-0 DE-627 ger DE-627 rda eng 570 610 VZ LING DE-30 fid 42.00 bkl 44.91 bkl Davyson, Eleanor verfasserin (orcid)0000-0002-7313-0530 aut Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD. Colocalization Depression Fatty acids Mendelian randomization Metabolome Multiomics Shen, Xueyi verfasserin aut Gadd, Danni A. verfasserin aut Bernabeu, Elena verfasserin aut Hillary, Robert F. verfasserin aut McCartney, Daniel L. verfasserin aut Adams, Mark verfasserin aut Marioni, Riccardo verfasserin aut McIntosh, Andrew M. verfasserin (orcid)0000-0002-0198-4588 aut Enthalten in Biological psychiatry Amsterdam [u.a.] : Elsevier Science, 1985 94, Seite 630-639 Online-Ressource (DE-627)306654296 (DE-600)1499907-9 (DE-576)115780807 1873-2402 nnns volume:94 pages:630-639 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-LING SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.00 Biologie: Allgemeines VZ 44.91 Psychiatrie Psychopathologie VZ AR 94 630-639
allfieldsSound	10.1016/j.biopsych.2023.01.027 doi (DE-627)ELV064396835 (ELSEVIER)S0006-3223(23)00055-0 DE-627 ger DE-627 rda eng 570 610 VZ LING DE-30 fid 42.00 bkl 44.91 bkl Davyson, Eleanor verfasserin (orcid)0000-0002-7313-0530 aut Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD. Colocalization Depression Fatty acids Mendelian randomization Metabolome Multiomics Shen, Xueyi verfasserin aut Gadd, Danni A. verfasserin aut Bernabeu, Elena verfasserin aut Hillary, Robert F. verfasserin aut McCartney, Daniel L. verfasserin aut Adams, Mark verfasserin aut Marioni, Riccardo verfasserin aut McIntosh, Andrew M. verfasserin (orcid)0000-0002-0198-4588 aut Enthalten in Biological psychiatry Amsterdam [u.a.] : Elsevier Science, 1985 94, Seite 630-639 Online-Ressource (DE-627)306654296 (DE-600)1499907-9 (DE-576)115780807 1873-2402 nnns volume:94 pages:630-639 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-LING SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.00 Biologie: Allgemeines VZ 44.91 Psychiatrie Psychopathologie VZ AR 94 630-639
language	English
source	Enthalten in Biological psychiatry 94, Seite 630-639 volume:94 pages:630-639
sourceStr	Enthalten in Biological psychiatry 94, Seite 630-639 volume:94 pages:630-639
format_phy_str_mv	Article
bklname	Biologie: Allgemeines Psychiatrie Psychopathologie
institution	findex.gbv.de
topic_facet	Colocalization Depression Fatty acids Mendelian randomization Metabolome Multiomics
dewey-raw	570
isfreeaccess_bool	false
container_title	Biological psychiatry
authorswithroles_txt_mv	Davyson, Eleanor @@aut@@ Shen, Xueyi @@aut@@ Gadd, Danni A. @@aut@@ Bernabeu, Elena @@aut@@ Hillary, Robert F. @@aut@@ McCartney, Daniel L. @@aut@@ Adams, Mark @@aut@@ Marioni, Riccardo @@aut@@ McIntosh, Andrew M. @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	306654296
dewey-sort	3570
id	ELV064396835
language_de	englisch
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We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. 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author	Davyson, Eleanor
spellingShingle	Davyson, Eleanor ddc 570 fid LING bkl 42.00 bkl 44.91 misc Colocalization misc Depression misc Fatty acids misc Mendelian randomization misc Metabolome misc Multiomics Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids
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topic_title	570 610 VZ LING DE-30 fid 42.00 bkl 44.91 bkl Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids Colocalization Depression Fatty acids Mendelian randomization Metabolome Multiomics
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title	Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids
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title_full	Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids
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title_sort	metabolomic investigation of major depressive disorder identifies a potentially causal association with polyunsaturated fatty acids
title_auth	Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids
abstract	Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD.
abstractGer	Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD.
abstract_unstemmed	Background: Metabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD.
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title_short	Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids
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author2	Shen, Xueyi Gadd, Danni A. Bernabeu, Elena Hillary, Robert F. McCartney, Daniel L. Adams, Mark Marioni, Riccardo McIntosh, Andrew M.
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We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.Results: A total of 191 metabolites tested were significantly associated with MDD (false discovery rate–corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.Conclusions: Our findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. 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Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids

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