@article {1341, title = {Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies.}, journal = {Eur Heart J}, volume = {33}, year = {2012}, month = {2012 Jan}, pages = {238-51}, abstract = {

AIMS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.

METHODS AND RESULTS: In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 {\texttimes} 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 {\texttimes} 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study.

CONCLUSION: Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, Coronary Artery Disease, Coronary Disease, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Middle Aged, Phospholipases A2, Polymorphism, Single Nucleotide}, issn = {1522-9645}, doi = {10.1093/eurheartj/ehr372}, author = {Grallert, Harald and Dupuis, Jos{\'e}e and Bis, Joshua C and Dehghan, Abbas and Barbalic, Maja and Baumert, Jens and Lu, Chen and Smith, Nicholas L and Uitterlinden, Andr{\'e} G and Roberts, Robert and Khuseyinova, Natalie and Schnabel, Renate B and Rice, Kenneth M and Rivadeneira, Fernando and Hoogeveen, Ron C and Fontes, Jo{\~a}o Daniel and Meisinger, Christa and Keaney, John F and Lemaitre, Rozenn and Aulchenko, Yurii S and Vasan, Ramachandran S and Ellis, Stephen and Hazen, Stanley L and van Duijn, Cornelia M and Nelson, Jeanenne J and M{\"a}rz, Winfried and Schunkert, Heribert and McPherson, Ruth M and Stirnadel-Farrant, Heide A and Psaty, Bruce M and Gieger, Christian and Siscovick, David and Hofman, Albert and Illig, Thomas and Cushman, Mary and Yamamoto, Jennifer F and Rotter, Jerome I and Larson, Martin G and Stewart, Alexandre F R and Boerwinkle, Eric and Witteman, Jacqueline C M and Tracy, Russell P and Koenig, Wolfgang and Benjamin, Emelia J and Ballantyne, Christie M} } @article {6769, title = {Contribution of Major Lifestyle Risk Factors for Incident Heart Failure in Older Adults: The Cardiovascular Health Study.}, journal = {JACC Heart Fail}, volume = {3}, year = {2015}, month = {2015 Jul}, pages = {520-8}, abstract = {

OBJECTIVES: The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults.

BACKGROUND: HF incurs high morbidity, mortality, and health care costs among adults >=65 years of age, which is the most rapidly growing segment of the U.S.

METHODS: We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity.

RESULTS: No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26\% and 22\% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95\% confidence interval [CI]: 0.63 to 0.86; leisure activity >=845 kcal/week vs. <845 kcal/week; HR: 0.78; 95\% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m(2), and not smoking were also independently associated with a lower risk of HF. Participants with >=4 healthy lifestyle factors had a 45\% (HR: 0.55; 95\% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed.

CONCLUSIONS: Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF.

}, keywords = {Aged, Alcohol Drinking, Cohort Studies, Diet, Female, Heart Failure, Humans, Incidence, Male, Motor Activity, Obesity, Proportional Hazards Models, Prospective Studies, Risk Factors, Sedentary Lifestyle, Smoking, United States}, issn = {2213-1787}, doi = {10.1016/j.jchf.2015.02.009}, author = {Del Gobbo, Liana C and Kalantarian, Shadi and Imamura, Fumiaki and Lemaitre, Rozenn and Siscovick, David S and Psaty, Bruce M and Mozaffarian, Dariush} } @article {7256, title = {KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.}, journal = {Proc Natl Acad Sci U S A}, volume = {113}, year = {2016}, month = {2016 Dec 13}, pages = {14372-14377}, abstract = {

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 {\texttimes} 10(-12)). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.

}, issn = {1091-6490}, doi = {10.1073/pnas.1611243113}, author = {Schumann, Gunter and Liu, Chunyu and O{\textquoteright}Reilly, Paul and Gao, He and Song, Parkyong and Xu, Bing and Ruggeri, Barbara and Amin, Najaf and Jia, Tianye and Preis, Sarah and Segura Lepe, Marcelo and Akira, Shizuo and Barbieri, Caterina and Baumeister, Sebastian and Cauchi, Stephane and Clarke, Toni-Kim and Enroth, Stefan and Fischer, Krista and H{\"a}llfors, Jenni and Harris, Sarah E and Hieber, Saskia and Hofer, Edith and Hottenga, Jouke-Jan and Johansson, Asa and Joshi, Peter K and Kaartinen, Niina and Laitinen, Jaana and Lemaitre, Rozenn and Loukola, Anu and Luan, Jian{\textquoteright}an and Lyytik{\"a}inen, Leo-Pekka and Mangino, Massimo and Manichaikul, Ani and Mbarek, Hamdi and Milaneschi, Yuri and Moayyeri, Alireza and Mukamal, Kenneth and Nelson, Christopher and Nettleton, Jennifer and Partinen, Eemil and Rawal, Rajesh and Robino, Antonietta and Rose, Lynda and Sala, Cinzia and Satoh, Takashi and Schmidt, Reinhold and Schraut, Katharina and Scott, Robert and Smith, Albert Vernon and Starr, John M and Teumer, Alexander and Trompet, Stella and Uitterlinden, Andr{\'e} G and Venturini, Cristina and Vergnaud, Anne-Claire and Verweij, Niek and Vitart, Veronique and Vuckovic, Dragana and Wedenoja, Juho and Yengo, Loic and Yu, Bing and Zhang, Weihua and Zhao, Jing Hua and Boomsma, Dorret I and Chambers, John and Chasman, Daniel I and Daniela, Toniolo and de Geus, Eco and Deary, Ian and Eriksson, Johan G and Esko, T{\~o}nu and Eulenburg, Volker and Franco, Oscar H and Froguel, Philippe and Gieger, Christian and Grabe, Hans J and Gudnason, Vilmundur and Gyllensten, Ulf and Harris, Tamara B and Hartikainen, Anna-Liisa and Heath, Andrew C and Hocking, Lynne and Hofman, Albert and Huth, Cornelia and Jarvelin, Marjo-Riitta and Jukema, J Wouter and Kaprio, Jaakko and Kooner, Jaspal S and Kutalik, Zolt{\'a}n and Lahti, Jari and Langenberg, Claudia and Lehtim{\"a}ki, Terho and Liu, Yongmei and Madden, Pamela A F and Martin, Nicholas and Morrison, Alanna and Penninx, Brenda and Pirastu, Nicola and Psaty, Bruce and Raitakari, Olli and Ridker, Paul and Rose, Richard and Rotter, Jerome I and Samani, Nilesh J and Schmidt, Helena and Spector, Tim D and Stott, David and Strachan, David and Tzoulaki, Ioanna and van der Harst, Pim and van Duijn, Cornelia M and Marques-Vidal, Pedro and Vollenweider, Peter and Wareham, Nicholas J and Whitfield, John B and Wilson, James and Wolffenbuttel, Bruce and Bakalkin, Georgy and Evangelou, Evangelos and Liu, Yun and Rice, Kenneth M and Desrivi{\`e}res, Sylvane and Kliewer, Steven A and Mangelsdorf, David J and M{\"u}ller, Christian P and Levy, Daniel and Elliott, Paul} } @article {7578, title = {Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0186456}, abstract = {

BACKGROUND: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences.

OBJECTIVE: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption.

DESIGN: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts.

RESULTS: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95\% statistical power to detect a genetic variant associated with effect size of 0.05\% for fish and 0.08\% for EPA+DHA.

CONCLUSIONS: These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

}, keywords = {Adult, Aged, Cohort Studies, Docosahexaenoic Acids, Eicosapentaenoic Acid, Europe, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Seafood, United States}, issn = {1932-6203}, doi = {10.1371/journal.pone.0186456}, author = {Mozaffarian, Dariush and Dashti, Hassan S and Wojczynski, Mary K and Chu, Audrey Y and Nettleton, Jennifer A and M{\"a}nnist{\"o}, Satu and Kristiansson, Kati and Reedik, M{\"a}gi and Lahti, Jari and Houston, Denise K and Cornelis, Marilyn C and van Rooij, Frank J A and Dimitriou, Maria and Kanoni, Stavroula and Mikkil{\"a}, Vera and Steffen, Lyn M and de Oliveira Otto, Marcia C and Qi, Lu and Psaty, Bruce and Djouss{\'e}, Luc and Rotter, Jerome I and Harald, Kennet and Perola, Markus and Rissanen, Harri and Jula, Antti and Krista, Fischer and Mihailov, Evelin and Feitosa, Mary F and Ngwa, Julius S and Xue, Luting and Jacques, Paul F and Per{\"a}l{\"a}, Mia-Maria and Palotie, Aarno and Liu, Yongmei and Nalls, Nike A and Ferrucci, Luigi and Hernandez, Dena and Manichaikul, Ani and Tsai, Michael Y and Kiefte-de Jong, Jessica C and Hofman, Albert and Uitterlinden, Andr{\'e} G and Rallidis, Loukianos and Ridker, Paul M and Rose, Lynda M and Buring, Julie E and Lehtim{\"a}ki, Terho and K{\"a}h{\"o}nen, Mika and Viikari, Jorma and Lemaitre, Rozenn and Salomaa, Veikko and Knekt, Paul and Metspalu, Andres and Borecki, Ingrid B and Cupples, L Adrienne and Eriksson, Johan G and Kritchevsky, Stephen B and Bandinelli, Stefania and Siscovick, David and Franco, Oscar H and Deloukas, Panos and Dedoussis, George and Chasman, Daniel I and Raitakari, Olli and Tanaka, Toshiko} } @article {9465, title = {Genome-Wide Association Studies and fine-mapping of genomic loci for n-3 and n-6 Polyunsaturated Fatty Acids in Hispanic American and African American Cohorts.}, journal = {Res Sq}, year = {2023}, month = {2023 Feb 24}, abstract = {

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of < 5 x 10 , we confirmed association of the signal and found evidence of two additional signals (in and ) within 200 kb of the originally reported signal. Outside of the region, we identified novel signals for arachidonic acid (AA) in Hispanic Americans located in/near genes including , , and spanning a > 9 Mb region on chromosome 11 (57.5Mb ~ 67.1Mb). Among these novel signals, we found associations unique to Hispanic Americans, including rs28364240, a missense variant for AA that is common in CHARGE Hispanic Americans but absent in other race/ancestry groups. Our study sheds light on the genetics of PUFAs and the value of investigating complex trait genetics across diverse ancestry populations.

}, doi = {10.21203/rs.3.rs-2073736/v1}, author = {Yang, Chaojie and Veenstra, Jenna and Bartz, Traci and Pahl, Matthew and Hallmark, Brian and Chen, Yii-Der Ida and Westra, Jason and Steffen, Lyn and Brown, Christopher and Siscovick, David and Tsai, Michael and Wood, Alexis and Rich, Stephen and Smith, Caren and O{\textquoteright}Connor, Timothy and Mozaffarian, Dariush and Grant, Struan and Chilton, Floyd and Tintle, Nathan and Lemaitre, Rozenn and Manichaikul, Ani} }