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At least 8 genes tied to obesity, all in brain

Dec. 16, 2008
Courtesy Nature
and World Science staff

Variants of at least eight genes are im­pli­cat­ed in sus­cep­ti­bil­ity to obes­ity, and all these genes ap­pear to work in the brain, sci­en­tists have found.

The find­ings are pub­lished this week in the re­search jour­nal Na­ture Ge­net­ics. 

A diagram of the brain in­clud­ing the hy­po­thal­a­mus. At least eight genes are im­pli­cat­ed in sus­cep­ti­bil­ity to obes­ity, and all of them ap­pear to work in the brain, sci­en­tists have found. (Image courtesy Nat'l Can­cer Inst.)
In the past, varia­t­ion in only two genes had been con­sist­ently im­pli­cat­ed in sus­cep­ti­bil­ity to com­mon forms of obes­ity, ac­cord­ing to Jo­el Hirsch­horn of the Broad In­sti­tute of Har­vard Uni­ver­s­ity and the Mas­sa­chu­setts In­sti­tute of Tech­nol­ogy and col­leagues.

Hirschhorn’s group an­a­lyzed a range of pre­vi­ous stud­ies com­pris­ing to­gether more than 30,000 par­ti­ci­pants, look­ing for ad­di­tion­al gene varia­t­ions as­so­ci­at­ed with body weight. 

They iden­ti­fied six new loca­t­ions in the ge­nome where they said gene varia­t­ion is as­so­ci­at­ed with weight. 

All these genes are found to be ac­ti­vate in the brain and in par­tic­u­lar the hy­po­thal­a­mus, they added. The hy­po­thal­a­mus is an almond-sized struc­ture deep with­in the brain known to reg­u­late body tem­per­a­ture, blood pres­sure, heart­beat, me­tab­o­lism of fats and car­bo­hy­drates, and blood sug­ar lev­els.

The find­ings high­light the role of brain cells in con­trol­ling food in­take, Hirsch­horn and col­leagues ar­gued.

In a sep­a­rate study al­so pub­lished in the jour­nal, Gud­mar Thor­leif­s­son of De­code Ge­net­ics in Rey­kja­vik, Ice­land and col­leagues car­ried out a similarly-sized study and iden­ti­fied sev­en ge­no­mic loca­t­ions as­so­ci­at­ed with meas­ures of obes­ity, most of which were al­so found in the Hirsch­horn stu­dy. 

Al­though com­mon gene vari­ants in these places each con­trib­ute only a small amount to varia­t­ion in body weight, the re­search­ers said, it may be that rare vari­ants at the same loca­t­ions will have great­er ef­fects on weight in some peo­ple.

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At least eight genes are implicated in susceptibility to obesity, and all of them appear to work in the brain, scientists have found. The findings are published this week in the research journal Nature Genetics. In the past, variation in only two genes had been consistently implicated in susceptibility to common forms of obesity, according to Joel Hirschhorn of the Broad Institute of Harvard University and the Massachusetts Institute of Tecchnology and colleagues. Hirschhorn and colleagues analyzed a range of previous studies as a whole comprising more than 30,000 participants to look for additional gene variations associated with body weight. They identified six new locations in the genome where they said gene variation is associated with body weight. All these genes are found to be activate in the brain and in particular the hypothalamus, they added. The hypothalamus is an almond-sized structure deep within the brain known to regulate body temperature, blood pressure, heartbeat, metabolism of fats and carbohydrates, and blood sugar levels. The finding highlight the role of brain cells in controlling of food intake, Hirschhorn and colleagues argued. In a separate study also published in the journal, Gudmar Thorleifsson of Decode Genetics in Reykjavik, Iceland and colleagues carried out a similarly-sized study and identified seven genomic locations associated with measures of obesity, most of which were also found in the Hirschhorn study. Although common gene variants in these places each contribute only a small amount to variation in body weight, the researchers said, it may be that rare variants at the same locations will have greater effects on weight in some people.