Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-04124-9
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Funding
- Bundesministerium fur Bildung und Forschung (BMBF) [01ER1206, 01ER1507]
- National Institutes of Health (NIH) [R01DK075787, R01DK107786, R01DK110113, U01HG007417]
- Swiss National Science Foundation [31003A_169929]
- SystemsX.ch [51RTP0_151019]
- German Research Foundation (DFG)
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [U01HG007417] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK075787, R01DK107786, R01DK110113] Funding Source: NIH RePORTER
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The problem of the genetics of related phenotypes is often addressed by analyzing adjusted-model traits, but such traits warrant cautious interpretation. Here, we adopt a joint view of adiposity traits in similar to 322,154 subjects (GIANT consortium). We classify 159 signals associated with body mass index (BMI), waist-to-hip ratio (WHR), or WHR adjusted for BMI (WHRadjBMI) at P < 5 x 10(-8), into four classes based on the direction of their effects on BMI and WHR. Our classes help differentiate adiposity genetics with respect to anthropometry, fat depots, and metabolic health. Class-specific Mendelian randomization reveals that variants associated with both WHR-decrease and BMI increase are linked to metabolically rather favorable adiposity through beneficial hip fat. Class-specific enrichment analyses implicate digestive systems as a pathway in adiposity genetics. Our results demonstrate that WHRadjBMI variants capture relevant effects of unexpected fat distribution given the BMI and that a joint view of the genetics underlying related phenotypes can inform on important biology.
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