Scientists say they have begun to crack the genetic code that helps determine when a girl becomes a woman.

A UK-led team located two genes on chromosomes six and nine that appear to strongly influence the age at which menstruation starts.

The Nature Genetics study also provides a clue for why girls who are shorter and fatter tend to get their periods months earlier than classmates.

The genes sit right next to DNA controlling height and weight.

A second paper, published in the same journal, also concludes that one of the two genes highlighted by the first study plays a key role in the timing of puberty in both girls and boys.

Reproductive lifespan is closely linked to the risk of developing conditions such as heart disease, breast cancer and osteoporosis.

It is thought that the female sex hormone oestrogen - produced at higher rates during a woman's reproductive life - raises the risk of these diseases.

Therefore, the earlier a woman goes through puberty, the more risk she may be at.

So the researchers say their work not only improves our understanding of the genetics underpinning development, it may ultimately aid the fight against disease.

However, they also accept that the onset of puberty is influenced by factors such as nutrition and exercise, and the effect of a single gene is likely to be relatively small.

Developing earlier

In the western world children are reaching puberty at younger and younger ages - some girls at the age of seven.

This study provides the first evidence that common genetic variants influence the time at which women reach sexual maturation
Researcher Dr Anna Murray from the Peninsula Medical School

Many blame rising obesity rates because, generally, girls who achieve menstruation earlier in life tend to have greater body mass index (BMI) and a higher ratio of fat compared to those who begin menstruation later.

From its analysis, a team led by Exeter's Peninsula Medical School predict one in 20 females carry two copies of each of the gene variations which result in menstruation starting earlier - approximately four and half months earlier than those with no copies of the gene variants.

In collaboration with research institutions across Europe and the US, they studied 17,510 women from across the world, including women of European descent who reported reaching menstruation of between nine and 17 years of age.

When they split the women up according to the age they began menstruating, certain gene patterns appeared.

Scanning the whole genome enabled them to hone in on these differences and pinpoint the exact genes most likely accountable.

Researcher Dr Anna Murray said: "This study provides the first evidence that common genetic variants influence the time at which women reach sexual maturation.

"Our findings also indicate a genetic basis for the associations between early menstruation and both height and BMI."

Biological mechanisms

Co-worker John Perry said: "Understanding the biological mechanisms behind reproductive lifespan may also help inform us about associated diseases that affect a lot of women as they get older, including diabetes, heart disease and breast cancer."

The second paper, led by the MRC Epidemiology Unit at Cambridge, analysed genetic information from thousands of people.

It linked a specific variant one of the two genes highlighted by the Exeter team - LIN28B - with earlier breast development in girls, and earlier voice breaking and pubic hair development in boys.

Lead researcher Dr Ken Ong said: "LIN28B works by controlling whether or not other genes are active.

"There are a number of such 'master switch' genes known, but this is the first evidence linking such a gene to growth and physical maturation."

Dr Aric Sigman, psychologist and fellow of the Royal Society of Medicine, said: "Early menstruation is a health issue because beyond being an inconvenient surprise for a girl and her parents, it's also associated with a higher risk of a variety of diseases and psychological problems.

"Girls maturing earlier are more likely to become depressed, delinquent, aggressive, socially withdrawn, suffer sleep problems drinking, smoking, drug abuse, lower self-esteem and suicide attempts.

"They're also more likely to exhibit poor academic performance in high school than on-time or later maturing peers.

"It is important that we understand why early menstruation occurs and these findings bring us closer to explaining this in some girls."

Three other papers, also published in Nature Genetics, throw up other candidate genes which appear to be involved in the onset of puberty.

科學(xué)家宣稱已經(jīng)開始破解有助于確定女孩成年的基因密碼。

一個由英國領(lǐng)導(dǎo)的科研小組確定了染色體中編號為六號和九號的兩條基因似乎強有力地影響了女性月經(jīng)開始的年齡。

《自然遺傳學(xué)》的研究也提供了一條線索，那就是矮胖的女孩為什么比班上的同學(xué)月經(jīng)初潮早幾個月。

基因與DNA一起控制身高和體重。

發(fā)表于該雜志的另一篇論文也斷定，由第一項研究強調(diào)的兩條基因中的一條對于女孩和男孩進入青春期的時間具有重要作用。

人的生殖期限與產(chǎn)生心臟病、乳腺癌和骨質(zhì)疏松癥的條件的危險緊密相連。

據(jù)說女性在生殖周期內(nèi)分泌更多雌性激素使得她們更易于染上這些疾病。

因此，女性經(jīng)歷青春期越早，就會越危險。

研究者認(rèn)為他們的工作不僅提高了我們對基因基礎(chǔ)發(fā)展的了解，還會最終有助于抵御疾病。

然而，他們也認(rèn)為青春期的開始也受到營養(yǎng)和運動等因素影響，單個基因的影響相對而言還是很小的。

發(fā)育更早

西方世界的小孩進入青春期的年齡越來越小——有些女孩七歲就進入青春期了。

許多人把此歸咎為越來越高的肥胖率，因為在通常情況下，與那些月經(jīng)初潮晚的女孩相比，月經(jīng)初潮早的女孩傾向于有更高的身體重量指數(shù)（BMI）和肥胖率。

據(jù)�？巳�特市的半島醫(yī)學(xué)院研究小組分析，20名女性中有一人擁有每個基因變異的兩個復(fù)制體，這兩個復(fù)制體導(dǎo)致了月經(jīng)初潮的提前到來，與那些沒有基因變異復(fù)制體的女孩相比，她們的月經(jīng)提前了四個半月。

他們還和歐洲、美國的研究機構(gòu)合作，研究了全世界17，510名女性，包括具有歐洲血統(tǒng)女子，據(jù)說她們在9至17歲有了月經(jīng)。

當(dāng)他們根據(jù)月經(jīng)初潮的年齡將女性分類，某些基因圖譜就顯現(xiàn)了。

審視整個基因組使他們消除了這些不同并且確定了真正起作用的基因。

研究者安娜·墨雷博士宣稱：“這項研究為基因變異影響女性性成熟的時間提供了第一個證據(jù)。

“我們的發(fā)現(xiàn)也顯示了月經(jīng)提前與身高和身體重量指數(shù)關(guān)系的基因基礎(chǔ)。”

生物機制

合作者約翰·佩里指出：“了解隱藏于生殖期限后的生物機制也可以幫助我們認(rèn)識影響某些女性早衰的疾病，包括糖尿病，心臟病和乳腺癌等。”

由位于劍橋大學(xué)的英國醫(yī)學(xué)研究理事會流行病學(xué)中心發(fā)表的第二篇論文分析了數(shù)千人的基因信息。

這篇論文把由埃克塞特市研究小組強調(diào)的兩條基因中的一個變異——LIN28B——與女孩乳房的提早發(fā)育、男孩提前變聲和陰毛提前生長進行聯(lián)合研究。

首席研究員肯·奧博士指出：“LIN28B通過控制其它是否活躍的基因而起作用。

“有許多已知的這樣的‘主開關(guān)’基因，但是基因與人的生長和身體成熟有聯(lián)系，這還是第一項證據(jù)。

心理學(xué)家、皇家醫(yī)學(xué)會成員艾日克·希格曼博士說：“月經(jīng)初潮提前是一個健康問題，因為對于女孩和她的父母來說，這都是一個令人措手不及的意外，同時也與容易產(chǎn)生多種疾病和心理問題有關(guān)。

“女孩發(fā)育越早就更容易變得憂郁、容易違法、好斗、孤僻、失眠、喝酒、抽煙、濫用藥物、缺乏自尊并有自殺企圖。

“與發(fā)育合適和晚發(fā)育的同齡人相比，她們也更容易在中學(xué)表現(xiàn)得學(xué)習(xí)成績很差。

“我們了解了為什么月經(jīng)初潮提前，這些發(fā)現(xiàn)也可以進一步解釋發(fā)生在某些女孩身上的現(xiàn)象，這些都很重要。”

發(fā)表于《自然遺傳學(xué)》的其余三篇論文，提出了另外的三個基因選項似乎也與青春期開始有關(guān)。