Mendelian Randomisation Study of Childhood BMI and Early Menarche
To infer the causal association between childhood BMI and age at menarche, we performed a mendelian randomisation analysis using twelve established “BMI-increasing” genetic variants as an instrumental variable (IV) for higher BMI. In 8,156 women of European descent from the EPIC-Norfolk cohort, heig...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Journal of Obesity |
| Online Access: | http://dx.doi.org/10.1155/2011/180729 |
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| author | Hannah S. Mumby Cathy E. Elks Shengxu Li Stephen J. Sharp Kay-Tee Khaw Robert N. Luben Nicholas J. Wareham Ruth J. F. Loos Ken K. Ong |
| author_facet | Hannah S. Mumby Cathy E. Elks Shengxu Li Stephen J. Sharp Kay-Tee Khaw Robert N. Luben Nicholas J. Wareham Ruth J. F. Loos Ken K. Ong |
| author_sort | Hannah S. Mumby |
| collection | DOAJ |
| description | To infer the causal association between childhood BMI and age at menarche, we performed a mendelian randomisation analysis using twelve established “BMI-increasing” genetic variants as an instrumental variable (IV) for higher BMI. In 8,156 women of European descent from the EPIC-Norfolk cohort, height was measured at age 39–77 years; age at menarche was self-recalled, as was body weight at age 20 years, and BMI at 20 was calculated as a proxy for childhood BMI. DNA was genotyped for twelve BMI-associated common variants (in/near FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, MTCH2, SEC16B, FAIM2 and SH2B1), and for each individual a “BMI-increasing-allele-score” was calculated by summing the number of BMI-increasing alleles across all 12 loci. Using this BMI-increasing-allele-score as an instrumental variable for BMI, each 1 kg/m2 increase in childhood BMI was predicted to result in a 6.5% (95% CI: 4.6–8.5%) higher absolute risk of early menarche (before age 12 years). While mendelian randomisation analysis is dependent on a number of assumptions, our findings support a causal effect of BMI on early menarche and suggests that increasing prevalence of childhood obesity will lead to similar trends in the prevalence of early menarche. |
| format | Article |
| id | doaj-art-94b28c0aecf64ff7bab57d00b17381e7 |
| institution | Kabale University |
| issn | 2090-0708 2090-0716 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Obesity |
| spelling | doaj-art-94b28c0aecf64ff7bab57d00b17381e72025-02-03T06:11:30ZengWileyJournal of Obesity2090-07082090-07162011-01-01201110.1155/2011/180729180729Mendelian Randomisation Study of Childhood BMI and Early MenarcheHannah S. Mumby0Cathy E. Elks1Shengxu Li2Stephen J. Sharp3Kay-Tee Khaw4Robert N. Luben5Nicholas J. Wareham6Ruth J. F. Loos7Ken K. Ong8MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, P.O. Box 285, Cambridge CB2 0QQ, UKMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, P.O. Box 285, Cambridge CB2 0QQ, UKMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, P.O. Box 285, Cambridge CB2 0QQ, UKMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, P.O. Box 285, Cambridge CB2 0QQ, UKDepartment of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 0SR, UKDepartment of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 0SR, UKMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, P.O. Box 285, Cambridge CB2 0QQ, UKMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, P.O. Box 285, Cambridge CB2 0QQ, UKMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, P.O. Box 285, Cambridge CB2 0QQ, UKTo infer the causal association between childhood BMI and age at menarche, we performed a mendelian randomisation analysis using twelve established “BMI-increasing” genetic variants as an instrumental variable (IV) for higher BMI. In 8,156 women of European descent from the EPIC-Norfolk cohort, height was measured at age 39–77 years; age at menarche was self-recalled, as was body weight at age 20 years, and BMI at 20 was calculated as a proxy for childhood BMI. DNA was genotyped for twelve BMI-associated common variants (in/near FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, MTCH2, SEC16B, FAIM2 and SH2B1), and for each individual a “BMI-increasing-allele-score” was calculated by summing the number of BMI-increasing alleles across all 12 loci. Using this BMI-increasing-allele-score as an instrumental variable for BMI, each 1 kg/m2 increase in childhood BMI was predicted to result in a 6.5% (95% CI: 4.6–8.5%) higher absolute risk of early menarche (before age 12 years). While mendelian randomisation analysis is dependent on a number of assumptions, our findings support a causal effect of BMI on early menarche and suggests that increasing prevalence of childhood obesity will lead to similar trends in the prevalence of early menarche.http://dx.doi.org/10.1155/2011/180729 |
| spellingShingle | Hannah S. Mumby Cathy E. Elks Shengxu Li Stephen J. Sharp Kay-Tee Khaw Robert N. Luben Nicholas J. Wareham Ruth J. F. Loos Ken K. Ong Mendelian Randomisation Study of Childhood BMI and Early Menarche Journal of Obesity |
| title | Mendelian Randomisation Study of Childhood BMI and Early Menarche |
| title_full | Mendelian Randomisation Study of Childhood BMI and Early Menarche |
| title_fullStr | Mendelian Randomisation Study of Childhood BMI and Early Menarche |
| title_full_unstemmed | Mendelian Randomisation Study of Childhood BMI and Early Menarche |
| title_short | Mendelian Randomisation Study of Childhood BMI and Early Menarche |
| title_sort | mendelian randomisation study of childhood bmi and early menarche |
| url | http://dx.doi.org/10.1155/2011/180729 |
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