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Article ; Online: Validation of the SQUASH physical activity questionnaire using accelerometry: The NEO study.

Terpstra, Sietse E S / Hoogervorst, Lotje A / van der Velde, Jeroen H P M / Mutsert, Renée de / van de Stadt, Lotte A / Rosendaal, Frits R / Kloppenburg, Margreet

Osteoarthritis and cartilage open

2024 Volume 6, Issue 2, Page(s) 100462

Abstract: Objective: To investigate the construct validity of the SQUASH (Short QUestionnaire to ASsess Health-enhancing physical activity).: Design: This is a cross-sectional analysis using baseline measurements from middle-aged participants in the ... ...

Abstract	Objective: To investigate the construct validity of the SQUASH (Short QUestionnaire to ASsess Health-enhancing physical activity). Design: This is a cross-sectional analysis using baseline measurements from middle-aged participants in the Netherlands Epidemiology of Obesity (NEO) study. The SQUASH consists of questions on eleven physical activities investigating days per week, average duration per day and intensity, leading to a summed score in Metabolic Equivalent of Task hours (MET h) per week. To assess convergent validity, a Spearman's rank correlation between SQUASH and ActiHeart was calculated. To assess extreme group validity, three groups expected to differ in SQUASH total physical activity outcome were compared. For discriminative validity, a Spearman's rank correlation between SQUASH physical activity and participant height was investigated. Results: SQUASH data were available for 6550 participants (mean age 56 years, 44% men, mean BMI 26.3, 15% with knee OA, 13% with hand OA). Median physical activity (interquartile range) was 118 (76; 154) MET h/week according to SQUASH and 75 (58; 99) according to ActiHeart. Convergent validity was weak (rho = 0.20). For all three extreme group comparisons, a statistically significant difference was present. Discriminative validity was present (rho = 0.01). Compared with the reference quintile, those with a discrepancy SQUASH > ActiHeart and SQUASH < ActiHeart were relatively younger and more often male. Conclusions: The construct validity of the SQUASH seems sub-optimal. Physical activity reported by the SQUASH was generally higher than reported by ActiHeart. Whether the differences between SQUASH and ActiHeart are e.g. due to different underlying domains, limitations to our study, or reflect true differences needs further investigation.
Language	English
Publishing date	2024-03-18
Publishing country	England
Document type	Journal Article
ISSN	2665-9131
ISSN (online)	2665-9131
DOI	10.1016/j.ocarto.2024.100462
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Article ; Online: Replacing Foods with a High-Glycemic Index and High in Saturated Fat by Alternatives with a Low Glycemic Index and Low Saturated Fat Reduces Hepatic Fat, Even in Isocaloric and Macronutrient Matched Conditions.

Basset-Sagarminaga, Jeremy / Roumans, Kay H M / Havekes, Bas / Mensink, Ronald P / Peters, Harry P F / Zock, Peter L / Mutsert, Renée de / Borén, Jan / Lindeboom, Lucas / Schrauwen, Patrick / Schrauwen-Hinderling, Vera B

Nutrients

2023 Volume 15, Issue 3

Abstract: Background: Current guidelines aim to limit the dietary glycemic index (GI) and intake of saturated fatty acids (SFA). Several studies have shown favorable effects of low-GI or low-SFA diets on intrahepatic lipid content (IHL), but these studies were ... ...

Abstract	Background: Current guidelines aim to limit the dietary glycemic index (GI) and intake of saturated fatty acids (SFA). Several studies have shown favorable effects of low-GI or low-SFA diets on intrahepatic lipid content (IHL), but these studies were performed under overfeeding conditions or extreme differences in GI or SFA to maximize the contrast between diets. By combining changes in GI and SFA, we can mimic how people can improve their diet in a realistic setting. Objectives: We investigated the effect on liver fat content and substrate metabolism of both reducing GI and replacing SFA with polyunsaturated fat in practically realistic amounts under isocaloric conditions. Design and methods: In a randomized crossover study, thirteen overweight participants consumed two diets, one high in GI and SFA (high GI/SFA) and one low in GI and SFA (low GI/SFA) with identical macronutrient composition, for two weeks each. Diets were equal in caloric content, consisted of habitual food items, and had a macronutrient composition that can be easily achieved in daily life. At the end of each intervention, IHL content/composition and liver glycogen were measured by magnetic resonance spectroscopy. Additionally, fasted and postprandial hepatic de novo lipogenesis and glycemic and metabolic responses were investigated. Results: IHL was significantly lower (-28%) after the two-week low-GI/SFA diet (2.4 ± 0.5% 95% CI [1.4, 3.4]) than after the two-week high-GI/SFA diet (3.3 ± 0.6% 95% CI [1.9, 4.7], Conclusions: Changes in macronutrient quality can already have drastic effects on liver fat content and postprandial glycemia after two weeks and even when energy content and the percentage of total fat and carbohydrate remains unchanged.
MeSH term(s)	Humans ; Glycemic Index ; Cross-Over Studies ; Fatty Acids/metabolism ; Dietary Fats/metabolism ; Diet, Fat-Restricted ; Liver/metabolism ; Nutrients ; Dietary Carbohydrates/metabolism
Chemical Substances	Fatty Acids ; Dietary Fats ; Dietary Carbohydrates
Language	English
Publishing date	2023-02-01
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15030735
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Article: Positive Associations of Dietary Marine Omega-3 Polyunsaturated Fatty Acids with Lung Function: A Meta-analysis (P18-087-19)

Patchen, Bonnie / Barr, R Graham / Cassano, Patricia / Dupuis, Josee / Eekelen, Ester van / Gharib, Sina / Hancock, Dana / Houston, Denise / Lahousse, Lies / Lemaitre, Rozenn / Manichaikul, Ani / Mutsert, Renee de / North, Kari / Saccone, Nancy / Steffen, Lyn / Terzikhan, Natalie / Wojczynski, Mary / Xu, Hanfei / Xu, Jiayi

Current developments in nutrition. 2019 June 13, v. 3, no. Supplement_1

2019

Abstract: Our previous study found positive associations between plasma levels of the omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA), and lung function, especially in current smokers. Given ... ...

Abstract	Our previous study found positive associations between plasma levels of the omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA), and lung function, especially in current smokers. Given that plasma n-3 PUFA concentrations are driven by dietary intake, we extended our prior findings to a larger sample by studying dietary n-3 PUFAs, including DHA, DPA, eicosapentanoic acid (EPA), and alpha-linolenic acid (ALA), and fish intake. Nine cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 37,077 black and white participants) contributed dietary intake and lung function data. In each cohort and each ancestry, separately, associations of dietary n-3 PUFA/fish intake with lung function were estimated in linear regression models. Models were extended to test for n-3 PUFA/fish × smoking status interaction. Fixed-effects meta-analysis was used to generate summarized effect estimates across the cohorts and ancestries. Dietary DPA, DHA, EPA, and fish intake were positively associated with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). ALA had little to no association with these lung function parameters. Associations were similar for black and white participants, and consistent in direction and magnitude across most cohorts. For all participants, 1 standard deviation (SD) higher intake of DPA (∼30 mg/d), DHA (∼200 mg/d), and EPA (∼150 mg/d) were associated with 12–16 mL higher FEV1 and 10–15 mL higher FVC. The effect estimates for fish were in the same direction but smaller in magnitude. Smoking modified the associations of DHA and EPA with FEV1 and FVC; 1 SD higher intake of DHA and EPA were associated with 28–32 mL higher FEV1 and 24–25 mL higher FVC in current smokers, 17–21 mL higher FEV1 and 7–12 mL higher FVC in former smokers, and little to no association in never smokers. Dietary DHA, DPA, and EPA, but not ALA, are positively associated with FEV1 and FVC, corroborating our previous findings for plasma n-3 PUFAs. This large cross-sectional meta-analysis shows that diets rich in marine n-3 PUFAs are associated with higher lung function, especially for current and former smokers. National Institutes of Health, NHLBI and NIDDK.
Keywords	alpha-linolenic acid ; ancestry ; docosahexaenoic acid ; docosapentaenoic acid ; eicosapentaenoic acid ; epidemiology ; fish ; fish consumption ; genomics ; heart ; lung function ; meta-analysis ; National Institutes of Health ; omega-3 fatty acids ; regression analysis ; smoking (habit) ; standard deviation
Language	English
Dates of publication	2019-0613
Publishing place	Oxford University Press
Document type	Article
ISSN	2475-2991
DOI	10.1093/cdn/nzz039.P18-087-19
Database	NAL-Catalogue (AGRICOLA)

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Article: Subjective global assessment of nutritional status is strongly associated with mortality in chronic dialysis patients

Mutsert, Renée de / Grootendorst, Diana C / Boeschoten, Elisabeth W / Brandts, Hans / Manen, Jeannette G. van / Krediet, Raymond T / Dekker, Friedo W

American journal of clinical nutrition AJN. 2009 Mar., v. 89, no. 3

2009

Abstract: BACKGROUND: The subjective global assessment of nutritional status (SGA) is used to assess the nutritional status of chronic dialysis patients, but longitudinal data in relation to mortality risk are lacking. OBJECTIVE: Our objective was to study the ... ...

Abstract	BACKGROUND: The subjective global assessment of nutritional status (SGA) is used to assess the nutritional status of chronic dialysis patients, but longitudinal data in relation to mortality risk are lacking. OBJECTIVE: Our objective was to study the long-term and time-dependent associations of the SGA with mortality risk in chronic dialysis patients. DESIGN: In a prospective, longitudinal, observational, multicenter study of incident dialysis patients, the 7-point SGA [7 = normal nutritional status; 1 = severe protein-energy wasting (PEW)] was assessed 3 and 6 mo after the start of dialysis and subsequently every 6 mo during 7 y of follow-up. With Cox regression analysis, we calculated hazard ratios (HRs) of the baseline and time-dependent SGA measurements, adjusted for age, sex, treatment modality, primary kidney diseases, and comorbidity. RESULTS: In total, 1601 patients were included [mean (±SD) age: 59 ± 15 y; 61% men; 23% with moderate PEW (SGA₄₋₅), and 5% with severe PEW (SGA₁₋₃)]. There was a dose-dependent trend of the 7-point SGA with mortality. Compared with a normal nutritional status at baseline, SGA₄₋₅ (HR: 1.6; 95% CI: 1.3, 1.9) and SGA₁₋₃ (HR: 2.1; 95% CI: 1.5, 2.8) were associated with an increase in 7-y mortality. Time-dependently, these associations were stronger: SGA₄₋₅ (HR: 2.1; 95% CI: 1.7, 2.5) and SGA₁₋₃ (HR: 5.0; 95% CI: 3.8, 6.5). CONCLUSIONS: In dialysis patients, PEW at baseline assessed with SGA was associated with a 2-fold increased mortality risk in 7 y of follow-up. Time-dependently, this association was even stronger, which indicated that PEW was associated with a remarkably high risk of short-term mortality. These data imply that the 7-point SGA may validly distinguish different degrees of PEW associated with increasing risks of mortality.
Keywords	nutrition assessment ; nutritional status ; mortality ; chronic diseases ; dialysis ; patients ; longitudinal studies ; risk assessment ; nutritional adequacy ; Netherlands
Language	English
Dates of publication	2009-03
Size	p. 787-793.
Publishing place	American Society for Clinical Nutrition
Document type	Article
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.

Dale, Caroline E / Fatemifar, Ghazaleh / Palmer, Tom M / White, Jon / Prieto-Merino, David / Zabaneh, Delilah / Engmann, Jorgen E L / Shah, Tina / Wong, Andrew / Warren, Helen R / McLachlan, Stela / Trompet, Stella / Moldovan, Max / Morris, Richard W / Sofat, Reecha / Kumari, Meena / Hyppönen, Elina / Jefferis, Barbara J / Gaunt, Tom R /

Circulation

2017 Volume 135, Issue 24, Page(s) 2373–2388

Abstract: Background: The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [ ... ...

Abstract	Background: The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. Methods: Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Results: Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28-1.71), similar to findings for BMI (1 SD≈4.6 kg/m Conclusions: Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.
MeSH term(s)	Adiposity/genetics ; Body Fat Distribution/methods ; Coronary Disease/epidemiology ; Coronary Disease/genetics ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/genetics ; Humans ; Longitudinal Studies ; Mendelian Randomization Analysis/methods ; Observational Studies as Topic/methods ; Polymorphism, Single Nucleotide/genetics ; Prospective Studies ; Stroke/epidemiology ; Stroke/genetics
Language	English
Publishing date	2017-05-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.116.026560
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Article ; Online: Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Surendran, Praveen / Feofanova, Elena V / Lahrouchi, Najim / Ntalla, Ioanna / Karthikeyan, Savita / Cook, James / Chen, Lingyan / Mifsud, Borbala / Yao, Chen / Kraja, Aldi T / Cartwright, James H / Hellwege, Jacklyn N / Giri, Ayush / Tragante, Vinicius / Thorleifsson, Gudmar / Liu, Dajiang J / Prins, Bram P / Stewart, Isobel D / Cabrera, Claudia P /

Eales, James M / Akbarov, Artur / Auer, Paul L / Bielak, Lawrence F / Bis, Joshua C / Braithwaite, Vickie S / Brody, Jennifer A / Daw, E Warwick / Warren, Helen R / Drenos, Fotios / Nielsen, Sune Fallgaard / Faul, Jessica D / Fauman, Eric B / Fava, Cristiano / Ferreira, Teresa / Foley, Christopher N / Franceschini, Nora / Gao, He / Giannakopoulou, Olga / Giulianini, Franco / Gudbjartsson, Daniel F / Guo, Xiuqing / Harris, Sarah E / Havulinna, Aki S / Helgadottir, Anna / Huffman, Jennifer E / Hwang, Shih-Jen / Kanoni, Stavroula / Kontto, Jukka / Larson, Martin G / Li-Gao, Ruifang / Lindström, Jaana / Lotta, Luca A / Lu, Yingchang / Luan, Jian'an / Mahajan, Anubha / Malerba, Giovanni / Masca, Nicholas G D / Mei, Hao / Menni, Cristina / Mook-Kanamori, Dennis O / Mosen-Ansorena, David / Müller-Nurasyid, Martina / Paré, Guillaume / Paul, Dirk S / Perola, Markus / Poveda, Alaitz / Rauramaa, Rainer / Richard, Melissa / Richardson, Tom G / Sepúlveda, Nuno / Sim, Xueling / Smith, Albert V / Smith, Jennifer A / Staley, James R / Stanáková, Alena / Sulem, Patrick / Thériault, Sébastien / Thorsteinsdottir, Unnur / Trompet, Stella / Varga, Tibor V / Velez Edwards, Digna R / Veronesi, Giovanni / Weiss, Stefan / Willems, Sara M / Yao, Jie / Young, Robin / Yu, Bing / Zhang, Weihua / Zhao, Jing-Hua / Zhao, Wei / Evangelou, Evangelos / Aeschbacher, Stefanie / Asllanaj, Eralda / Blankenberg, Stefan / Bonnycastle, Lori L / Bork-Jensen, Jette / Brandslund, Ivan / Braund, Peter S / Burgess, Stephen / Cho, Kelly / Christensen, Cramer / Connell, John / Mutsert, Renée de / Dominiczak, Anna F / Dörr, Marcus / Eiriksdottir, Gudny / Farmaki, Aliki-Eleni / Gaziano, J Michael / Grarup, Niels / Grove, Megan L / Hallmans, Göran / Hansen, Torben / Have, Christian T / Heiss, Gerardo / Jørgensen, Marit E / Jousilahti, Pekka / Kajantie, Eero / Kamat, Mihir / Käräjämäki, AnneMari / Karpe, Fredrik / Koistinen, Heikki A / Kovesdy, Csaba P / Kuulasmaa, Kari / Laatikainen, Tiina / Lannfelt, Lars / Lee, I-Te / Lee, Wen-Jane / Linneberg, Allan / Martin, Lisa W / Moitry, Marie / Nadkarni, Girish / Neville, Matt J / Palmer, Colin N A / Papanicolaou, George J / Pedersen, Oluf / Peters, James / Poulter, Neil / Rasheed, Asif / Rasmussen, Katrine L / Rayner, N William / Mägi, Reedik / Renström, Frida / Rettig, Rainer / Rossouw, Jacques / Schreiner, Pamela J / Sever, Peter S / Sigurdsson, Emil L / Skaaby, Tea / Sun, Yan V / Sundstrom, Johan / Thorgeirsson, Gudmundur / Esko, Tõnu / Trabetti, Elisabetta / Tsao, Philip S / Tuomi, Tiinamaija / Turner, Stephen T / Tzoulaki, Ioanna / Vaartjes, Ilonca / Vergnaud, Anne-Claire / Willer, Cristen J / Wilson, Peter W F / Witte, Daniel R / Yonova-Doing, Ekaterina / Zhang, He / Aliya, Naheed / Almgren, Peter / Amouyel, Philippe / Asselbergs, Folkert W / Barnes, Michael R / Blakemore, Alexandra I / Boehnke, Michael / Bots, Michiel L / Bottinger, Erwin P / Buring, Julie E / Chambers, John C / Chen, Yii-Der Ida / Chowdhury, Rajiv / Conen, David / Correa, Adolfo / Davey Smith, George / Boer, Rudolf A de / Deary, Ian J / Dedoussis, George / Deloukas, Panos / Di Angelantonio, Emanuele / Elliott, Paul / Felix, Stephan B / Ferrières, Jean / Ford, Ian / Fornage, Myriam / Franks, Paul W / Franks, Stephen / Frossard, Philippe / Gambaro, Giovanni / Gaunt, Tom R / Groop, Leif / Gudnason, Vilmundur / Harris, Tamara B / Hayward, Caroline / Hennig, Branwen J / Herzig, Karl-Heinz / Ingelsson, Erik / Tuomilehto, Jaakko / Järvelin, Marjo-Riitta / Jukema, J Wouter / Kardia, Sharon L R / Kee, Frank / Kooner, Jaspal S / Kooperberg, Charles / Launer, Lenore J / Lind, Lars / Loos, Ruth J F / Majumder, Abdulla Al Shafi / Laakso, Markku / McCarthy, Mark I / Melander, Olle / Mohlke, Karen L / Murray, Alison D / Nordestgaard, Børge Grønne / Orho-Melander, Marju / Packard, Chris J / Padmanabhan, Sandosh / Palmas, Walter / Polasek, Ozren / Porteous, David J / Prentice, Andrew M / Province, Michael A / Relton, Caroline L / Rice, Kenneth / Ridker, Paul M / Rolandsson, Olov / Rosendaal, Frits R / Rotter, Jerome I / Rudan, Igor / Salomaa, Veikko / Samani, Nilesh J / Sattar, Naveed / Sheu, Wayne H-H / Smith, Blair H / Soranzo, Nicole / Spector, Timothy D / Starr, John M / Sebert, Sylvain / Taylor, Kent D / Lakka, Timo A / Timpson, Nicholas J / Tobin, Martin D / van der Harst, Pim / van der Meer, Peter / Ramachandran, Vasan S / Verweij, Niek / Virtamo, Jarmo / Völker, Uwe / Weir, David R / Zeggini, Eleftheria / Charchar, Fadi J / Wareham, Nicholas J / Langenberg, Claudia / Tomaszewski, Maciej / Butterworth, Adam S / Caulfield, Mark J / Danesh, John / Edwards, Todd L / Holm, Hilma / Hung, Adriana M / Lindgren, Cecilia M / Liu, Chunyu / Manning, Alisa K / Morris, Andrew P / Morrison, Alanna C / O'Donnell, Christopher J / Psaty, Bruce M / Saleheen, Danish / Stefansson, Kari / Boerwinkle, Eric / Chasman, Daniel I / Levy, Daniel / Newton-Cheh, Christopher / Munroe, Patricia B / Howson, Joanna M M

Nature genetics

2021 Volume 53, Issue 5, Page(s) 762

Language	English
Publishing date	2021-03-16
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-021-00832-z
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Article ; Online: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Nature genetics

2020 Volume 52, Issue 12, Page(s) 1314–1332

Abstract: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele ... ...

Abstract	Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10
MeSH term(s)	Blood Pressure/genetics ; GATA5 Transcription Factor/genetics ; Gene Frequency/genetics ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Genotype ; Humans ; Hypertension/genetics ; Mutation/genetics ; Phospholipase C beta/genetics ; Polymorphism, Single Nucleotide/genetics
Chemical Substances	GATA5 Transcription Factor ; GATA5 protein, human ; PLCB3 protein, human (EC 3.1.4.11) ; Phospholipase C beta (EC 3.1.4.11)
Language	English
Publishing date	2020-11-23
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-020-00713-x
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Article ; Online: Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Justice, Anne E / Karaderi, Tugce / Highland, Heather M / Young, Kristin L / Graff, Mariaelisa / Lu, Yingchang / Turcot, Valérie / Auer, Paul L / Fine, Rebecca S / Guo, Xiuqing / Schurmann, Claudia / Lempradl, Adelheid / Marouli, Eirini / Mahajan, Anubha / Winkler, Thomas W / Locke, Adam E / Medina-Gomez, Carolina / Esko, Tõnu / Vedantam, Sailaja /

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Nature genetics

2019 Volume 51, Issue 3, Page(s) 452–469

Abstract: Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site ... ...

Abstract	Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
MeSH term(s)	Animals ; Body Fat Distribution/methods ; Body Mass Index ; Case-Control Studies ; Drosophila/genetics ; Exome/genetics ; Female ; Gene Frequency/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Variation/genetics ; Genome-Wide Association Study/methods ; Homeostasis/genetics ; Humans ; Lipids/genetics ; Male ; Proteins/genetics ; Risk Factors ; Waist-Hip Ratio/methods
Chemical Substances	Lipids ; Proteins
Language	English
Publishing date	2019-02-18
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-018-0334-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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