Genetic loci associated with circulating phospholipid trans fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium

被引：48

作者：

Mozaffarian, Dariush ^{[1
,6
,7
,8
]}

Kabagambe, Edmond K. ^{[17
]}

Johnson, Catherine ^{[9
]}

Lemaitre, Rozenn N. ^{[9
]}

Manichaikul, Ani ^{[15
,16
]}

Sun, Qi ^{[6
,8
]}

Foy, Millennia ^{[20
]}

Wang, Lu ^{[4
]}

Wiener, Howard ^{[24
]}

Irvin, Marguerite R. ^{[24
]}

Rich, Stephen S. ^{[15
]}

Wu, Hongyu ^{[8
]}

Jensen, Majken K. ^{[8
]}

Chasman, Daniel I. ^{[3
,4
]}

Chu, Audrey Y. ^{[4
]}

Fornage, Myriam ^{[20
,21
]}

Steffen, Lyn ^{[18
]}

King, Irena B.

McKnight, Barbara ^{[10
,11
]}

Psaty, Bruce M. ^{[9
,12
,13
,14
]}

Djousse, Luc ^{[5
]}

Chen, Ida Y-D ^{[22
]}

Wu, Jason H. Y. ^{[23
]}

Siscovick, David S. ^{[9
,12
]}

Ridker, Paul M. ^{[2
,4
]}

Tsai, Michael Y. ^{[19
]}

Rimm, Eric B. ^{[6
,7
,8
]}

Hu, Frank B. ^{[6
,7
,8
]}

Arnett, Donna K. ^{[24
]}

机构：

[1] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA

[2] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA

[6] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA

[8] Harvard Univ, Sch Med, Dept Nutr, Boston, MA USA

[9] Univ Washington, Sch Publ Hlth, Dept Med, Seattle, WA 98195 USA

[10] Univ Washington, Sch Publ Hlth, Sch Med, Seattle, WA 98195 USA

[11] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA

[12] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA

[13] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA

[14] Res Inst, Grp Hlth Collaborat, Seattle, WA USA

[15] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA USA

[16] Univ Virginia, Div Biostat, Dept Publ Hlth Sci, Charlottesville, VA USA

[17] Vanderbilt Univ, Med Ctr, Div Epidemiol, Dept Med, Nashville, TN 37235 USA

[18] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN USA

[19] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA

[20] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Inst Mol Med, Houston, TX 77030 USA

[21] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol, Houston, TX 77030 USA

[22] Harbor UCLA, Med Ctr, Dept Pediat, Div Genom Outcomes, Los Angeles, CA USA

[23] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia

[24] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA

来源：

AMERICAN JOURNAL OF CLINICAL NUTRITION | 2015年 / 101卷 / 02期

关键词：

arachidonic acid; genome-wide association; meta-analysis; phospholipid; trans fatty acids; CORONARY-ARTERY-DISEASE; AGING RESEARCH; HEART-DISEASE; SYSTEMIC INFLAMMATION; CARDIOVASCULAR HEALTH; METABOLIC SYNDROME; AFRICAN-AMERICANS; ARACHIDONIC-ACID; RISK-FACTORS; PLASMA;

D O I：

10.3945/ajcn.114.094557

中图分类号：

R15 [营养卫生、食品卫生]; TS201 [基础科学];

学科分类号：

100403 ;

摘要：

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 (beta = 0.0035, P = 4.90 x 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 (beta = 0.0053, P = 1.05 x 10(-6)) and Chinese Americans (beta = 0.0028, P = 0.002) but not African Americans (beta = 0.0009, P = 0.34); however, in African Americans, fine mapping identified a top hit in FADS2 associated with cis/trans-18:2 (rs174579: beta = 0.0118, P = 4.05 X 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 cisltrans-18:2 was nearly eliminated in European-ancestry participants (p-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.

引用

页码：398 / 406

页数：9

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