Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study
The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population‐specific genetic variants associated with liver fat. We conducted a genome‐wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) asse...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2020-08-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1533 |
| _version_ | 1827834153699115008 |
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| author | S. Lani Park Yuqing Li Xin Sheng Victor Hom Lucy Xia Kechen Zhao Loreall Pooler V. Wendy Setiawan Unhee Lim Kristine R. Monroe Lynne R. Wilkens Bruce S. Kristal Johanna W. Lampe Meredith Hullar John Shepherd Lenora L. M. Loo Thomas Ernst Adrian A. Franke Maarit Tiirikainen Christopher A. Haiman Daniel O. Stram Loïc Le Marchand Iona Cheng |
| author_facet | S. Lani Park Yuqing Li Xin Sheng Victor Hom Lucy Xia Kechen Zhao Loreall Pooler V. Wendy Setiawan Unhee Lim Kristine R. Monroe Lynne R. Wilkens Bruce S. Kristal Johanna W. Lampe Meredith Hullar John Shepherd Lenora L. M. Loo Thomas Ernst Adrian A. Franke Maarit Tiirikainen Christopher A. Haiman Daniel O. Stram Loïc Le Marchand Iona Cheng |
| author_sort | S. Lani Park |
| collection | DOAJ |
| description | The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population‐specific genetic variants associated with liver fat. We conducted a genome‐wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population‐based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin‐like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10−15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA‐IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10−8) was also observed. Rs7724941 was associated with HOMA‐IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high‐density lipoprotein (beta = −0.046; P = 0.04), and sex hormone binding globulin (beta = −0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association. |
| first_indexed | 2024-03-12T05:44:58Z |
| format | Article |
| id | doaj.art-e8f054f12a4940a3a7f7e07d5df0cc9c |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-03-12T05:44:58Z |
| publishDate | 2020-08-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-e8f054f12a4940a3a7f7e07d5df0cc9c2023-09-03T05:40:51ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2020-08-01481112112310.1002/hep4.1533Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype StudyS. Lani Park0Yuqing Li1Xin Sheng2Victor Hom3Lucy Xia4Kechen Zhao5Loreall Pooler6V. Wendy Setiawan7Unhee Lim8Kristine R. Monroe9Lynne R. Wilkens10Bruce S. Kristal11Johanna W. Lampe12Meredith Hullar13John Shepherd14Lenora L. M. Loo15Thomas Ernst16Adrian A. Franke17Maarit Tiirikainen18Christopher A. Haiman19Daniel O. Stram20Loïc Le Marchand21Iona Cheng22Keck School of Medicine University of Southern California Los Angeles CAUSADepartment of Epidemiology and Biostatistics University of California, San Francisco San Francisco CAUSAKeck School of Medicine University of Southern California Los Angeles CAUSAKeck School of Medicine University of Southern California Los Angeles CAUSAKeck School of Medicine University of Southern California Los Angeles CAUSAKeck School of Medicine University of Southern California Los Angeles CAUSAKeck School of Medicine University of Southern California Los Angeles CAUSAKeck School of Medicine University of Southern California Los Angeles CAUSAUniversity of Hawaii Cancer Center University of Hawaii at Manoa Honolulu HIUSAKeck School of Medicine University of Southern California Los Angeles CAUSAUniversity of Hawaii Cancer Center University of Hawaii at Manoa Honolulu HIUSADivision of Sleep and Circadian Disorders Department of Medicine Brigham and Women's Hospital Boston MAUSAFred Hutchinson Cancer Research Center Seattle WAUSAFred Hutchinson Cancer Research Center Seattle WAUSAUniversity of Hawaii Cancer Center University of Hawaii at Manoa Honolulu HIUSAUniversity of Hawaii Cancer Center University of Hawaii at Manoa Honolulu HIUSADepartment of Diagnostic Radiology and Nuclear Medicine University of Maryland School of Medicine Baltimore MDUSAUniversity of Hawaii Cancer Center University of Hawaii at Manoa Honolulu HIUSAUniversity of Hawaii Cancer Center University of Hawaii at Manoa Honolulu HIUSAKeck School of Medicine University of Southern California Los Angeles CAUSAKeck School of Medicine University of Southern California Los Angeles CAUSAUniversity of Hawaii Cancer Center University of Hawaii at Manoa Honolulu HIUSADepartment of Epidemiology and Biostatistics University of California, San Francisco San Francisco CAUSAThe global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population‐specific genetic variants associated with liver fat. We conducted a genome‐wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population‐based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin‐like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10−15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA‐IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10−8) was also observed. Rs7724941 was associated with HOMA‐IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high‐density lipoprotein (beta = −0.046; P = 0.04), and sex hormone binding globulin (beta = −0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.https://doi.org/10.1002/hep4.1533 |
| spellingShingle | S. Lani Park Yuqing Li Xin Sheng Victor Hom Lucy Xia Kechen Zhao Loreall Pooler V. Wendy Setiawan Unhee Lim Kristine R. Monroe Lynne R. Wilkens Bruce S. Kristal Johanna W. Lampe Meredith Hullar John Shepherd Lenora L. M. Loo Thomas Ernst Adrian A. Franke Maarit Tiirikainen Christopher A. Haiman Daniel O. Stram Loïc Le Marchand Iona Cheng Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study Hepatology Communications |
| title | Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study |
| title_full | Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study |
| title_fullStr | Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study |
| title_full_unstemmed | Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study |
| title_short | Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study |
| title_sort | genome wide association study of liver fat the multiethnic cohort adiposity phenotype study |
| url | https://doi.org/10.1002/hep4.1533 |
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