Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations

被引：3

作者：

Anwar, Mohammad Yaser ^{[1
]}

Baldassari, Antoine R. ^{[1
]}

Polikowsky, Hannah G. ^{[2
]}

Sitlani, Colleen M. ^{[3
]}

Highland, Heather M. ^{[1
]}

Chami, Nathalie ^{[4
]}

Chen, Hung-Hsin ^{[2
]}

Graff, Mariaelisa ^{[1
]}

Howard, Annie Green ^{[5
,6
]}

Jung, Su Yon ^{[7
,8
]}

Petty, Lauren E. ^{[2
]}

Wang, Zhe ^{[4
]}

Zhu, Wanying ^{[2
]}

Buyske, Steven ^{[9
]}

Cheng, Iona ^{[10
]}

Kaplan, Robert ^{[11
]}

Kooperberg, Charles ^{[12
]}

Loos, Ruth J. F. ^{[4
]}

Peters, Ulrike ^{[12
]}

McCormick, Joseph B. ^{[13
]}

Fisher-Hoch, Susan P. ^{[13
]}

Avery, Christy L. ^{[1
,6
]}

Taylor, Kira C. ^{[14
]}

Below, Jennifer E. ^{[2
]}

North, Kari E. ^{[1
]}

机构：

[1] Univ N Carolina, Dept Epidemiol, CVD Genet Epidemiol Lab, 123 West Franklin St,Fl 4,Room A7, Chapel Hill, NC 27599 USA

[2] Vanderbilt Univ, Vanderbilt Genet Inst, Med Ctr, Nashville, TN 37232 USA

[3] Univ Washington, Dept Med, Seattle, WA 98195 USA

[4] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[5] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA

[6] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27516 USA

[7] Univ Calif Los Angeles, Sch Nursing, Translat Sci Sect, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[9] Rutgers State Univ, Dept Stat, Piscataway, NJ 08854 USA

[10] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94115 USA

[11] Albert Einstein Coll Med, Bronx, NY 10461 USA

[12] Fred Hutchinson Canc Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA

[13] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Brownsville Reg Campus, Brownsville, TX 78520 USA

[14] Univ Louisville, Dept Epidemiol & Populat Hlth, Sch Publ Hlth & Informat Sci, Louisville, KY 40202 USA

来源：

BMC MEDICAL GENOMICS | 2022年 / 15卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Obesity; Inflammation; Genetic pleiotropy; Hispanic Americans; C-REACTIVE PROTEIN; GENOME-WIDE ASSOCIATION; ETHNIC-DIFFERENCES; METABOLIC SYNDROME; LEPR GENE; OBESITY; HEALTH; FAT; EXPRESSION; INSULIN;

D O I：

10.1186/s12920-022-01352-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations. Methods Using multi-trait Adaptive Sum of Powered Score (aSPU) method, we examined individual and shared genetic effects underlying inflammatory (CRP) and adiposity-related traits (Body Mass Index [BMI]), and central adiposity (Waist to Hip Ratio [WHR]) in HLA participating in the Population Architecture Using Genomics and Epidemiology (PAGE) cohort (N = 35,871) with replication of effects in the Cameron County Hispanic Cohort (CCHC) which consists of Mexican American individuals. Results Of the > 16 million SNPs tested, variants representing 7 independent loci were found to illustrate significant association with multiple traits. Two out of 7 variants were replicated at statistically significant level in multi-trait analyses in CCHC. The lead variant on APOE (rs439401) and rs11208712 were found to harbor multi-trait associations with adiposity and inflammation. Conclusions Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development.

引用

页数：11

共 79 条

[1]

Abecasis GR, 2012, Nature, V491, P56, DOI DOI 10.1038/nature11632

[2] Cardiovascular Biology of Interleukin-6 [J].

Abeywardena, Mahinda Y. ;

Leifert, Wayne R. ;

Warnes, Kirsty E. ;

Varghese, Jose N. ;

Head, Richard J. .

CURRENT PHARMACEUTICAL DESIGN, 2009, 15 (15) :1809-1821

[3] The inflammation: Lipoprotein cycle [J].

Barter, P .

ATHEROSCLEROSIS SUPPLEMENTS, 2005, 6 (02) :15-20

[4] The association of markers of inflammation with weight change in older adults:: the Cardiovascular Health Study [J].

Barzilay, J. I. ;

Forsberg, C. ;

Heckbert, S. R. ;

Cushman, M. ;

Newman, A. B. .

INTERNATIONAL JOURNAL OF OBESITY, 2006, 30 (09) :1362-1367

[5]

Belloy ME., 2020, ALZHEIMERS DEMENT, V16, DOI [10.1002/alz.043539, DOI 10.1002/ALZ.043539]

[6] Strategies for Enriching Variant Coverage in Candidate Disease Loci on a Multiethnic Genotyping Array [J].

Bien, Stephanie A. ;

Wojcik, Genevieve L. ;

Zubair, Niha ;

Gignoux, Christopher R. ;

Martin, Alicia R. ;

Kocarnik, Jonathan M. ;

Martin, Lisa W. ;

Buyske, Steven ;

Haessler, Jeffrey ;

Walker, Ryan W. ;

Cheng, Iona ;

Graff, Mariaelisa ;

Xia, Lucy ;

Franceschini, Nora ;

Matise, Tara ;

James, Regina ;

Hindorff, Lucia ;

Le Marchand, Loic ;

North, Kari E. ;

Haiman, Christopher A. ;

Peters, Ulrike ;

Loos, Ruth J. F. ;

Kooperberg, Charles L. ;

Bustamante, Carlos D. ;

Kenny, Eimear E. ;

Carlson, Christopher S. .

PLOS ONE, 2016, 11 (12)

[7] Postprandial variations of plasma inflammatory markers in abdominally obese men [J].

Blackburn, Patricia ;

Despres, Jean-Pierre ;

Lamarche, Benoit ;

Tremblay, Angelo ;

Bergeron, Jean ;

Lemieux, Isabelle ;

Couillard, Charles .

OBESITY, 2006, 14 (10) :1747-1754

[8] Genetic variants on chromosome 19 (rs439401 and rs4420638) are associated with obesity and high blood pressure in the Algerian population [J].

Boulenouar, H. ;

Benchekor, S. Mediene ;

Djellouli, H. Ouhaibi ;

Hetraf, S. Larjam ;

Houti, L. ;

Hammani-Medjaoui, I. .

VAVILOVSKII ZHURNAL GENETIKI I SELEKTSII, 2019, 23 (05) :608-614

[9] Relation of C-Reactive Protein to Abdominal Adiposity [J].

Brooks, Gabriel C. ;

Blaha, Michael J. ;

Blumenthal, Roger S. .

AMERICAN JOURNAL OF CARDIOLOGY, 2010, 106 (01) :56-61

[10] Genome-wide patterns of population structure and admixture among Hispanic/Latino populations [J].

Bryc, Katarzyna ;

Velez, Christopher ;

Karafet, Tatiana ;

Moreno-Estrada, Andres ;

Reynolds, Andy ;

Auton, Adam ;

Hammer, Michael ;

Bustamante, Carlos D. ;

Ostrer, Harry .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 :8954-8961

← 1 2 3 4 5 6 7 8 →