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Adiposity and genetic factors in relation to triglycerides and triglyceride-rich lipoproteins in the women's genome health study

Ahmad, Shafqat LU ; Mora, Samia; Franks, Paul W. LU ; Orho-Melander, Marju LU ; Ridker, Paul M.; Hu, Frank B. and Chasman, Daniel I. (2018) In Clinical Chemistry 64(1). p.231-241
Abstract

BACKGROUND: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown. METHODS: We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TGwGRS) based on 40 published TG-associated singlenucleotide polymorphisms was calculated using published effect estimates. RESULTS: Comparing overweight (BMI ≥ 25 kg/m2) and... (More)

BACKGROUND: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown. METHODS: We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TGwGRS) based on 40 published TG-associated singlenucleotide polymorphisms was calculated using published effect estimates. RESULTS: Comparing overweight (BMI ≥ 25 kg/m2) and normal weight (BMI = 25 kg/m2) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant (Pinteraction = 0.014). Metaanalyses combining results forWGHSBMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction (Pinteraction = 0.001). Similarly, we observed differential association of the TG-wGRS with TG (Pinteraction = 0.006) in strata of WC ( <80 cm vs <80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects (Pinteraction = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all Pinteractions = 0.0001). The differential effects were strongest for very large TG-rich lipoprotein. CONCLUSIONS: Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Chemistry
volume
64
issue
1
pages
11 pages
publisher
American Association for Clinical Chemistry
external identifiers
  • scopus:85040055787
ISSN
0009-9147
DOI
10.1373/clinchem.2017.280545
language
English
LU publication?
yes
id
e9c27247-2596-42f4-ba21-de85ec904f66
date added to LUP
2018-01-22 09:34:15
date last changed
2018-01-23 03:00:14
@article{e9c27247-2596-42f4-ba21-de85ec904f66,
  abstract     = {<p>BACKGROUND: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown. METHODS: We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TGwGRS) based on 40 published TG-associated singlenucleotide polymorphisms was calculated using published effect estimates. RESULTS: Comparing overweight (BMI ≥ 25 kg/m<sup>2</sup>) and normal weight (BMI = 25 kg/m<sup>2</sup>) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant (P<sub>interaction</sub> = 0.014). Metaanalyses combining results forWGHSBMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction (P<sub>interaction</sub> = 0.001). Similarly, we observed differential association of the TG-wGRS with TG (P<sub>interaction</sub> = 0.006) in strata of WC ( &lt;80 cm vs &lt;80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects (P<sub>interaction</sub> = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all Pinteractions = 0.0001). The differential effects were strongest for very large TG-rich lipoprotein. CONCLUSIONS: Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.</p>},
  author       = {Ahmad, Shafqat and Mora, Samia and Franks, Paul W. and Orho-Melander, Marju and Ridker, Paul M. and Hu, Frank B. and Chasman, Daniel I.},
  issn         = {0009-9147},
  language     = {eng},
  number       = {1},
  pages        = {231--241},
  publisher    = {American Association for Clinical Chemistry},
  series       = {Clinical Chemistry},
  title        = {Adiposity and genetic factors in relation to triglycerides and triglyceride-rich lipoproteins in the women's genome health study},
  url          = {http://dx.doi.org/10.1373/clinchem.2017.280545},
  volume       = {64},
  year         = {2018},
}