@article {6325, title = {Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest.}, journal = {Heart Rhythm}, volume = {11}, year = {2014}, month = {2014 Mar}, pages = {471-7}, abstract = {

BACKGROUND: There is limited information on genetic factors associated with sudden cardiac arrest (SCA).

OBJECTIVE: To assess the association of common variation in genes in fatty acid pathways with SCA risk.

METHODS: We selected 85 candidate genes and 1155 single nucleotide polymorphisms (SNPs) tagging common variation in each gene. We investigated the SNP associations with SCA in a population-based case-control study. Cases (n = 2160) were from a repository of SCA in the greater Seattle area. Controls (n = 2615), frequency-matched on age and sex, were from the same area. We used linear logistic regression to examine SNP associations with SCA. We performed permutation-based p-min tests to account for multiple comparisons within each gene. The SNP associations with a corrected P value of <.05 were then examined in a meta-analysis of these SNP associations in 9 replication studies totaling 2129 SCA cases and 23,833 noncases.

RESULTS: Eight SNPs in or near 8 genes were associated with SCA risk in the discovery study, one of which was nominally significant in the replication phase (rs7737692, minor allele frequency 36\%, near the LPCAT1 gene). For each copy of the minor allele, rs7737692 was associated with 13\% lower SCA risk (95\% confidence interval -21\% to -5\%) in the discovery phase and 9\% lower SCA risk (95\% confidence interval -16\% to -1\%) in the replication phase.

CONCLUSIONS: While none of the associations reached significance with Bonferroni correction, a common genetic variant near LPCAT1, a gene involved in the remodeling of phospholipids, was nominally associated with incident SCA risk. Further study is needed to validate this observation.

}, keywords = {1-Acylglycerophosphocholine O-Acyltransferase, Aged, Algorithms, Alleles, Case-Control Studies, Death, Sudden, Cardiac, Fatty Acids, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Risk Factors}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2014.01.008}, author = {Lemaitre, Rozenn N and Johnson, Catherine O and Hesselson, Stephanie and Sotoodehnia, Nona and Sotoodhenia, Nona and McKnight, Barbara and Sitlani, Colleen M and Rea, Thomas D and King, Irena B and Kwok, Pui-Yan and Mak, Angel and Li, Guo and Brody, Jennifer and Larson, Eric and Mozaffarian, Dariush and Psaty, Bruce M and Huertas-Vazquez, Adriana and Tardif, Jean-Claude and Albert, Christine M and Lyytik{\"a}inen, Leo-Pekka and Arking, Dan E and K{\"a}{\"a}b, Stefan and Huikuri, Heikki V and Krijthe, Bouwe P and Eijgelsheim, Mark and Wang, Ying A and Reinier, Kyndaron and Lehtim{\"a}ki, Terho and Pulit, Sara L and Brugada, Ramon and M{\"u}ller-Nurasyid, Martina and Newton-Cheh, Chris H and Karhunen, Pekka J and Stricker, Bruno H and Goyette, Philippe and Rotter, Jerome I and Chugh, Sumeet S and Chakravarti, Aravinda and Jouven, Xavier and Siscovick, David S} } @article {6685, title = {Genetic loci associated with circulating phospholipid trans fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.}, journal = {Am J Clin Nutr}, volume = {101}, year = {2015}, month = {2015 Feb}, pages = {398-406}, abstract = {

BACKGROUND: Circulating trans fatty acids (TFAs), which cannot be synthesized by humans, are linked to adverse health outcomes. Although TFAs are obtained from diet, little is known about subsequent influences (e.g., relating to incorporation, metabolism, or intercompetition with other fatty acids) that could alter circulating concentrations and possibly modulate or mediate impacts on health.

OBJECTIVE: The objective was to elucidate novel biologic pathways that may influence circulating TFAs by evaluating associations between common genetic variation and TFA biomarkers.

DESIGN: We performed meta-analyses using 7 cohorts of European-ancestry participants (n = 8013) having measured genome-wide variation in single-nucleotide polymorphisms (SNPs) and circulating TFA biomarkers (erythrocyte or plasma phospholipids), including trans-16:1n-7, total trans-18:1, trans/cis-18:2, cis/trans-18:2, and trans/trans-18:2. We further evaluated SNPs with genome-wide significant associations among African Americans (n = 1082), Chinese Americans (n = 669), and Hispanic Americans (n = 657) from 2 of these cohorts.

RESULTS: Among European-ancestry participants, 31 SNPs in or near the fatty acid desaturase (FADS) 1 and 2 cluster were associated with cis/trans-18:2; a top hit was rs174548 (β = 0.0035, P = 4.90 {\texttimes} 10(-15)), an SNP previously associated with circulating n-3 and n-6 polyunsaturated fatty acid concentrations. No significant association was identified for other TFAs. rs174548 in FADS1/2 was also associated with cis/trans-18:2 in Hispanic Americans (β = 0.0053, P = 1.05 {\texttimes} 10(-6)) and Chinese Americans (β = 0.0028, P = 0.002) but not African Americans (β = 0.0009, P = 0.34); however, in African Americans, fine mapping identified a top hit in FADS2 associated with cis/trans-18:2 (rs174579: β = 0.0118, P = 4.05 {\texttimes} 10(-5)). The association between rs174548 and cis/trans-18:2 remained significant after further adjustment for individual circulating n-3 and n-6 fatty acids, except arachidonic acid. After adjustment for arachidonic acid concentrations, the association between rs174548 and cis/trans-18:2 was nearly eliminated in European-ancestry participants (β-coefficient reduced by 86\%), with similar reductions in Hispanic Americans and Chinese Americans.

CONCLUSIONS: Our findings provide novel evidence for genetic regulation of cis/trans-18:2 by the FADS1/2 cluster and suggest that this regulation may be influenced/mediated by concentrations of arachidonic acid, an n-6 polyunsaturated fat.

}, keywords = {African Americans, Arachidonic Acid, Asian Americans, Biomarkers, European Continental Ancestry Group, Fatty Acids, Omega-6, Gene Frequency, Genetic Association Studies, Genetic Loci, Genotyping Techniques, Humans, Phospholipids, Polymorphism, Single Nucleotide, Trans Fatty Acids}, issn = {1938-3207}, doi = {10.3945/ajcn.114.094557}, author = {Mozaffarian, Dariush and Kabagambe, Edmond K and Johnson, Catherine O and Lemaitre, Rozenn N and Manichaikul, Ani and Sun, Qi and Foy, Millennia and Wang, Lu and Wiener, Howard and Irvin, Marguerite R and Rich, Stephen S and Wu, Hongyu and Jensen, Majken K and Chasman, Daniel I and Chu, Audrey Y and Fornage, Myriam and Steffen, Lyn and King, Irena B and McKnight, Barbara and Psaty, Bruce M and Djouss{\'e}, Luc and Chen, Ida Y-D and Wu, Jason H Y and Siscovick, David S and Ridker, Paul M and Tsai, Michael Y and Rimm, Eric B and Hu, Frank B and Arnett, Donna K} }