Meta-analysis of genome-wide linkage studies in BMI and obesity

Catherine L. Saunders, Benedetta D. Chiodini, Pak Sham, Cathryn M. Lewis, Victor Abkevich, Adebowale A. Adeyemo, Mariza De Andrade, Rector Arya, Gerald S. Berenson, John Blangero, Michael Boehnke, Ingrid B. Borecki, Yvon C. Chagnon, Wei Chen, Anthony G. Comuzzie, Hong Wen Deng, Ravindranath Duggirala, Mary F. Feitosa, Philippe Froguel, Robert L. Hanson & 20 others Johannes Hebebrand, Patricia Huezo-Dias, Ahmed H. Kissebah, Weidong Li, Amy Luke, Lisa J. Martin, Matthew Nash, Miina Öhman, Lyle J. Palmer, Leena Peltonen, Markus Perola, R. Arlen Price, Susan Redline, Sathanur R. Srinivasan, Michael P. Stern, Steven Stone, Heather Stringham, Stephen T Turner, Cisca Wijmenga, David A. Collier

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry. Results: Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01). Conclusion: Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.

Original languageEnglish (US)
Pages (from-to)2263-2275
Number of pages13
JournalObesity
Volume15
Issue number9
DOIs
StatePublished - 2007

Fingerprint

Meta-Analysis
Obesity
Genome
Hypertension
Genes
Genetic Linkage
Genetic Heterogeneity
Adiposity
Type 2 Diabetes Mellitus
Chromosomes
Research

Keywords

  • Adiposity
  • Diabetes
  • Genetics
  • Hypertension
  • Meta-analysis

ASJC Scopus subject areas

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

Cite this

Saunders, C. L., Chiodini, B. D., Sham, P., Lewis, C. M., Abkevich, V., Adeyemo, A. A., ... Collier, D. A. (2007). Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity, 15(9), 2263-2275. https://doi.org/10.1038/oby.2007.269

Meta-analysis of genome-wide linkage studies in BMI and obesity. / Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; De Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Öhman, Miina; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen T; Wijmenga, Cisca; Collier, David A.

In: Obesity, Vol. 15, No. 9, 2007, p. 2263-2275.

Research output: Contribution to journalArticle

Saunders, CL, Chiodini, BD, Sham, P, Lewis, CM, Abkevich, V, Adeyemo, AA, De Andrade, M, Arya, R, Berenson, GS, Blangero, J, Boehnke, M, Borecki, IB, Chagnon, YC, Chen, W, Comuzzie, AG, Deng, HW, Duggirala, R, Feitosa, MF, Froguel, P, Hanson, RL, Hebebrand, J, Huezo-Dias, P, Kissebah, AH, Li, W, Luke, A, Martin, LJ, Nash, M, Öhman, M, Palmer, LJ, Peltonen, L, Perola, M, Price, RA, Redline, S, Srinivasan, SR, Stern, MP, Stone, S, Stringham, H, Turner, ST, Wijmenga, C & Collier, DA 2007, 'Meta-analysis of genome-wide linkage studies in BMI and obesity', Obesity, vol. 15, no. 9, pp. 2263-2275. https://doi.org/10.1038/oby.2007.269
Saunders CL, Chiodini BD, Sham P, Lewis CM, Abkevich V, Adeyemo AA et al. Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity. 2007;15(9):2263-2275. https://doi.org/10.1038/oby.2007.269
Saunders, Catherine L. ; Chiodini, Benedetta D. ; Sham, Pak ; Lewis, Cathryn M. ; Abkevich, Victor ; Adeyemo, Adebowale A. ; De Andrade, Mariza ; Arya, Rector ; Berenson, Gerald S. ; Blangero, John ; Boehnke, Michael ; Borecki, Ingrid B. ; Chagnon, Yvon C. ; Chen, Wei ; Comuzzie, Anthony G. ; Deng, Hong Wen ; Duggirala, Ravindranath ; Feitosa, Mary F. ; Froguel, Philippe ; Hanson, Robert L. ; Hebebrand, Johannes ; Huezo-Dias, Patricia ; Kissebah, Ahmed H. ; Li, Weidong ; Luke, Amy ; Martin, Lisa J. ; Nash, Matthew ; Öhman, Miina ; Palmer, Lyle J. ; Peltonen, Leena ; Perola, Markus ; Price, R. Arlen ; Redline, Susan ; Srinivasan, Sathanur R. ; Stern, Michael P. ; Stone, Steven ; Stringham, Heather ; Turner, Stephen T ; Wijmenga, Cisca ; Collier, David A. / Meta-analysis of genome-wide linkage studies in BMI and obesity. In: Obesity. 2007 ; Vol. 15, No. 9. pp. 2263-2275.
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AU - Saunders, Catherine L.

AU - Chiodini, Benedetta D.

AU - Sham, Pak

AU - Lewis, Cathryn M.

AU - Abkevich, Victor

AU - Adeyemo, Adebowale A.

AU - De Andrade, Mariza

AU - Arya, Rector

AU - Berenson, Gerald S.

AU - Blangero, John

AU - Boehnke, Michael

AU - Borecki, Ingrid B.

AU - Chagnon, Yvon C.

AU - Chen, Wei

AU - Comuzzie, Anthony G.

AU - Deng, Hong Wen

AU - Duggirala, Ravindranath

AU - Feitosa, Mary F.

AU - Froguel, Philippe

AU - Hanson, Robert L.

AU - Hebebrand, Johannes

AU - Huezo-Dias, Patricia

AU - Kissebah, Ahmed H.

AU - Li, Weidong

AU - Luke, Amy

AU - Martin, Lisa J.

AU - Nash, Matthew

AU - Öhman, Miina

AU - Palmer, Lyle J.

AU - Peltonen, Leena

AU - Perola, Markus

AU - Price, R. Arlen

AU - Redline, Susan

AU - Srinivasan, Sathanur R.

AU - Stern, Michael P.

AU - Stone, Steven

AU - Stringham, Heather

AU - Turner, Stephen T

AU - Wijmenga, Cisca

AU - Collier, David A.

PY - 2007

Y1 - 2007

N2 - Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry. Results: Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01). Conclusion: Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.

AB - Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry. Results: Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01). Conclusion: Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.

KW - Adiposity

KW - Diabetes

KW - Genetics

KW - Hypertension

KW - Meta-analysis

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