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Meta‐Analysis of Genome‐wide Linkage Studies in BMI and Obesity
Author(s) -
Saunders Catherine L.,
Chiodini Benedetta D.,
Sham Pak,
Lewis Cathryn M.,
Abkevich Victor,
Adeyemo Adebowale A.,
Andrade Mariza,
Arya Rector,
Berenson Gerald S.,
Blangero John,
Boehnke Michael,
Borecki Ingrid B.,
Chag Yvon C.,
Chen Wei,
Comuzzie Anthony G.,
Deng HongWen,
Duggirala Ravindranath,
Feitosa Mary F.,
Froguel Philippe,
Hanson Robert L.,
Hebebrand Johannes,
HuezoDias 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,
Wijmenga Cisca,
Collier David A.
Publication year - 2007
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2007.269
Subject(s) - obesity , medicine , genetic linkage , body mass index , type 2 diabetes , odds ratio , locus (genetics) , linkage (software) , meta analysis , genetics , diabetes mellitus , biology , gene , endocrinology
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.