Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study.
Few studies have explored the genetic underpinnings of intra-abdominal visceral fat deposition, which varies substantially by sex and race/ethnicity. Among 1,787 participants in the Multiethnic Cohort (MEC)-Adiposity Phenotype Study (MEC-APS), we conducted a genome-wide association study (GWAS) of t...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0279932 |
| _version_ | 1797788277289254912 |
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| author | Samantha A Streicher Unhee Lim S Lani Park Yuqing Li Xin Sheng Victor Hom Lucy Xia Loreall Pooler John Shepherd Lenora W M Loo Thomas Ernst Steven Buchthal Adrian A Franke Maarit Tiirikainen Lynne R Wilkens Christopher A Haiman Daniel O Stram Iona Cheng Loïc Le Marchand |
| author_facet | Samantha A Streicher Unhee Lim S Lani Park Yuqing Li Xin Sheng Victor Hom Lucy Xia Loreall Pooler John Shepherd Lenora W M Loo Thomas Ernst Steven Buchthal Adrian A Franke Maarit Tiirikainen Lynne R Wilkens Christopher A Haiman Daniel O Stram Iona Cheng Loïc Le Marchand |
| author_sort | Samantha A Streicher |
| collection | DOAJ |
| description | Few studies have explored the genetic underpinnings of intra-abdominal visceral fat deposition, which varies substantially by sex and race/ethnicity. Among 1,787 participants in the Multiethnic Cohort (MEC)-Adiposity Phenotype Study (MEC-APS), we conducted a genome-wide association study (GWAS) of the percent visceral adiposity tissue (VAT) area out of the overall abdominal area, averaged across L1-L5 (%VAT), measured by abdominal magnetic resonance imaging (MRI). A genome-wide significant signal was found on chromosome 2q14.3 in the sex-combined GWAS (lead variant rs79837492: Beta per effect allele = -4.76; P = 2.62 × 10-8) and in the male-only GWAS (lead variant rs2968545: (Beta = -6.50; P = 1.09 × 10-9), and one suggestive variant was found at 13q12.11 in the female-only GWAS (rs79926925: Beta = 6.95; P = 8.15 × 10-8). The negatively associated variants were most common in European Americans (T allele of rs79837492; 5%) and African Americans (C allele of rs2968545; 5%) and not observed in Japanese Americans, whereas the positively associated variant was most common in Japanese Americans (C allele of rs79926925, 5%), which was all consistent with the racial/ethnic %VAT differences. In a validation step among UK Biobank participants (N = 23,699 of mainly British and Irish ancestry) with MRI-based VAT volume, both rs79837492 (Beta = -0.026, P = 0.019) and rs2968545 (Beta = -0.028, P = 0.010) were significantly associated in men only (n = 11,524). In the MEC-APS, the association between rs79926925 and plasma sex hormone binding globulin levels reached statistical significance in females, but not in males, with adjustment for total adiposity (Beta = -0.24; P = 0.028), on the log scale. Rs79837492 and rs2968545 are located in intron 5 of CNTNAP5, and rs79926925, in an intergenic region between GJB6 and CRYL1. These novel findings differing by sex and racial/ethnic group warrant replication in additional diverse studies with direct visceral fat measurements. |
| first_indexed | 2024-03-13T01:33:20Z |
| format | Article |
| id | doaj.art-c4c1f0c10fd9466f85019a5fa4ea1bc9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-13T01:33:20Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-c4c1f0c10fd9466f85019a5fa4ea1bc92023-07-04T05:32:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01181e027993210.1371/journal.pone.0279932Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study.Samantha A StreicherUnhee LimS Lani ParkYuqing LiXin ShengVictor HomLucy XiaLoreall PoolerJohn ShepherdLenora W M LooThomas ErnstSteven BuchthalAdrian A FrankeMaarit TiirikainenLynne R WilkensChristopher A HaimanDaniel O StramIona ChengLoïc Le MarchandFew studies have explored the genetic underpinnings of intra-abdominal visceral fat deposition, which varies substantially by sex and race/ethnicity. Among 1,787 participants in the Multiethnic Cohort (MEC)-Adiposity Phenotype Study (MEC-APS), we conducted a genome-wide association study (GWAS) of the percent visceral adiposity tissue (VAT) area out of the overall abdominal area, averaged across L1-L5 (%VAT), measured by abdominal magnetic resonance imaging (MRI). A genome-wide significant signal was found on chromosome 2q14.3 in the sex-combined GWAS (lead variant rs79837492: Beta per effect allele = -4.76; P = 2.62 × 10-8) and in the male-only GWAS (lead variant rs2968545: (Beta = -6.50; P = 1.09 × 10-9), and one suggestive variant was found at 13q12.11 in the female-only GWAS (rs79926925: Beta = 6.95; P = 8.15 × 10-8). The negatively associated variants were most common in European Americans (T allele of rs79837492; 5%) and African Americans (C allele of rs2968545; 5%) and not observed in Japanese Americans, whereas the positively associated variant was most common in Japanese Americans (C allele of rs79926925, 5%), which was all consistent with the racial/ethnic %VAT differences. In a validation step among UK Biobank participants (N = 23,699 of mainly British and Irish ancestry) with MRI-based VAT volume, both rs79837492 (Beta = -0.026, P = 0.019) and rs2968545 (Beta = -0.028, P = 0.010) were significantly associated in men only (n = 11,524). In the MEC-APS, the association between rs79926925 and plasma sex hormone binding globulin levels reached statistical significance in females, but not in males, with adjustment for total adiposity (Beta = -0.24; P = 0.028), on the log scale. Rs79837492 and rs2968545 are located in intron 5 of CNTNAP5, and rs79926925, in an intergenic region between GJB6 and CRYL1. These novel findings differing by sex and racial/ethnic group warrant replication in additional diverse studies with direct visceral fat measurements.https://doi.org/10.1371/journal.pone.0279932 |
| spellingShingle | Samantha A Streicher Unhee Lim S Lani Park Yuqing Li Xin Sheng Victor Hom Lucy Xia Loreall Pooler John Shepherd Lenora W M Loo Thomas Ernst Steven Buchthal Adrian A Franke Maarit Tiirikainen Lynne R Wilkens Christopher A Haiman Daniel O Stram Iona Cheng Loïc Le Marchand Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study. PLoS ONE |
| title | Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study. |
| title_full | Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study. |
| title_fullStr | Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study. |
| title_full_unstemmed | Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study. |
| title_short | Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study. |
| title_sort | genome wide association study of abdominal mri measured visceral fat the multiethnic cohort adiposity phenotype study |
| url | https://doi.org/10.1371/journal.pone.0279932 |
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