Genetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S. Hispanics/Latinos

Qibin Qi, Stephanie M. Gogarten, Leslie S. Emery, Tin Louie, Adrienne Stilp, Jianwen Cai, Neil Schneiderman, M. Larissa Avilés-Santa, Robert C. Kaplan, Kari E. North, Cathy C. Laurie, Ruth J F Loos, Carmen R. Isasi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined. Methods: Previously genome-wide association study-identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos. Results: The C-allele (frequency = 26%) of rs2943650 was significantly associated with higher BF% overall (β = 0.34 ± 0.11% per allele; P = 0.002) and in women (β = 0.41 ± 0.14% per C-allele; P = 0.003), but not in men (β = 0.28 ± 0.18% per C-allele; P = 0.11), though there was no significant sex difference. Using the inverse normal-transformed data to compare effect sizes, it was found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (β = 0.054 ± 0.018SD vs. β = 0.008 ± 0.011SD per C-allele; P = 0.03). The BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P < 0.05). Conclusions: This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared with European women.

Original languageEnglish (US)
Pages (from-to)2407-2413
Number of pages7
JournalObesity
Volume24
Issue number11
DOIs
StatePublished - Nov 1 2016

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Metabolome
Adiposity
Hispanic Americans
Adipose Tissue
Alleles
Genome-Wide Association Study
Gene Frequency
Sex Characteristics
HDL Cholesterol
Insulin Resistance
Fasting
Hemoglobins
Triglycerides
Insulin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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Genetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S. Hispanics/Latinos. / Qi, Qibin; Gogarten, Stephanie M.; Emery, Leslie S.; Louie, Tin; Stilp, Adrienne; Cai, Jianwen; Schneiderman, Neil; Avilés-Santa, M. Larissa; Kaplan, Robert C.; North, Kari E.; Laurie, Cathy C.; Loos, Ruth J F; Isasi, Carmen R.

In: Obesity, Vol. 24, No. 11, 01.11.2016, p. 2407-2413.

Research output: Contribution to journalArticle

Qi, Q, Gogarten, SM, Emery, LS, Louie, T, Stilp, A, Cai, J, Schneiderman, N, Avilés-Santa, ML, Kaplan, RC, North, KE, Laurie, CC, Loos, RJF & Isasi, CR 2016, 'Genetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S. Hispanics/Latinos', Obesity, vol. 24, no. 11, pp. 2407-2413. https://doi.org/10.1002/oby.21624
Qi, Qibin ; Gogarten, Stephanie M. ; Emery, Leslie S. ; Louie, Tin ; Stilp, Adrienne ; Cai, Jianwen ; Schneiderman, Neil ; Avilés-Santa, M. Larissa ; Kaplan, Robert C. ; North, Kari E. ; Laurie, Cathy C. ; Loos, Ruth J F ; Isasi, Carmen R. / Genetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S. Hispanics/Latinos. In: Obesity. 2016 ; Vol. 24, No. 11. pp. 2407-2413.
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abstract = "Objective: Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined. Methods: Previously genome-wide association study-identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF{\%}) and multiple metabolic traits were tested among up to 12,730 adults (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos. Results: The C-allele (frequency = 26{\%}) of rs2943650 was significantly associated with higher BF{\%} overall (β = 0.34 ± 0.11{\%} per allele; P = 0.002) and in women (β = 0.41 ± 0.14{\%} per C-allele; P = 0.003), but not in men (β = 0.28 ± 0.18{\%} per C-allele; P = 0.11), though there was no significant sex difference. Using the inverse normal-transformed data to compare effect sizes, it was found that the association with BF{\%} was stronger in Hispanic/Latino women than that previously reported in European women (β = 0.054 ± 0.018SD vs. β = 0.008 ± 0.011SD per C-allele; P = 0.03). The BF{\%}-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P < 0.05). Conclusions: This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF{\%} in Hispanic/Latino women compared with European women.",
author = "Qibin Qi and Gogarten, {Stephanie M.} and Emery, {Leslie S.} and Tin Louie and Adrienne Stilp and Jianwen Cai and Neil Schneiderman and Avil{\'e}s-Santa, {M. Larissa} and Kaplan, {Robert C.} and North, {Kari E.} and Laurie, {Cathy C.} and Loos, {Ruth J F} and Isasi, {Carmen R.}",
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T1 - Genetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S. Hispanics/Latinos

AU - Qi, Qibin

AU - Gogarten, Stephanie M.

AU - Emery, Leslie S.

AU - Louie, Tin

AU - Stilp, Adrienne

AU - Cai, Jianwen

AU - Schneiderman, Neil

AU - Avilés-Santa, M. Larissa

AU - Kaplan, Robert C.

AU - North, Kari E.

AU - Laurie, Cathy C.

AU - Loos, Ruth J F

AU - Isasi, Carmen R.

PY - 2016/11/1

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N2 - Objective: Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined. Methods: Previously genome-wide association study-identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos. Results: The C-allele (frequency = 26%) of rs2943650 was significantly associated with higher BF% overall (β = 0.34 ± 0.11% per allele; P = 0.002) and in women (β = 0.41 ± 0.14% per C-allele; P = 0.003), but not in men (β = 0.28 ± 0.18% per C-allele; P = 0.11), though there was no significant sex difference. Using the inverse normal-transformed data to compare effect sizes, it was found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (β = 0.054 ± 0.018SD vs. β = 0.008 ± 0.011SD per C-allele; P = 0.03). The BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P < 0.05). Conclusions: This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared with European women.

AB - Objective: Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined. Methods: Previously genome-wide association study-identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos. Results: The C-allele (frequency = 26%) of rs2943650 was significantly associated with higher BF% overall (β = 0.34 ± 0.11% per allele; P = 0.002) and in women (β = 0.41 ± 0.14% per C-allele; P = 0.003), but not in men (β = 0.28 ± 0.18% per C-allele; P = 0.11), though there was no significant sex difference. Using the inverse normal-transformed data to compare effect sizes, it was found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (β = 0.054 ± 0.018SD vs. β = 0.008 ± 0.011SD per C-allele; P = 0.03). The BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P < 0.05). Conclusions: This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared with European women.

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