期刊
HUMAN MOLECULAR GENETICS
卷 24, 期 12, 页码 3582-3594出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddv097
关键词
-
资金
- Gates Cambridge Trust
- Canadian Institutes of Health Research University Industry
- Glaxo-SmithKline
- Sanofi Aventis Global
- Sanofi Aventis Canada
- McGill University
- Genome Quebec Innovation Centre
- Heart and Stroke Foundation of Canada
- Canadian Institutes of Health Research
- Heart and Stroke Foundation of Ontario
- Genome Canada through Ontario Genomics Institute
- Aventis
- National Institute of Health [DK072488, DK088231]
- National Heart, Lung, and Blood Institute, National Institutes of Health [U01 HL076419, U01 HL65899, P01 HL083069, T32 HL07427]
- Swedish Research Council
- Swedish Heart-Lung Foundation
- Swedish Diabetes Association
- Novo Nordisk
- Federal Ministry of Education and Research (BMBF), Germany [FKZ: 01EO1002]
- Danish Council for Independent Research [DFF-1333-00124]
- British Heart Foundation [RG/08/014/24067] Funding Source: researchfish
- Cancer Research UK [14136] Funding Source: researchfish
- Medical Research Council [MC_UU_12011/1, U1475000001, G1000143, U1475000002, MR/L003120/1, G0401527, MC_UU_12011/2, MC_UP_A620_1014, MC_U147585827, MC_UP_A620_1015, MC_UU_12015/1, MC_U106179471] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10165, NF-SI-0512-10114, NF-SI-0508-10082, NF-SI-0513-10085, NF-SI-0512-10135] Funding Source: researchfish
- MRC [MC_UU_12011/2, MR/L003120/1, MC_UP_A620_1015, MC_U147585827, MC_UU_12015/1] Funding Source: UKRI
Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) a parts per thousand yen 40 kg/m(2)], but their contribution to common obesity (BMI a parts per thousand yen 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 x 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 x 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (beta = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (beta = 0.02, 95% CI 0.00-0.03; P = 5.57 x 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据