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WASHINGTON - Chinese, American scientists have sequenced and analyzed a portion of genomes of over 140,000 pregnant women in China, the largest-scale genetic analysis of Chinese people to date, revealing associations between genes and birth outcomes, including the birth of twins and a woman"s age at first pregnancy.

The study published on Thursday in the journal Cell also allowed researchers to reconstruct the intermarriage of different ethnic groups in China, and promised to help identify genes that make people susceptible to infectious diseases.

Researchers from BGI-Shenzhen used data from non-invasive prenatal testing (NIPT) to sequence randomly 6 to 10 percent of each mother"s genome.

"Although non-invasive prenatal testing is low-pass sequencing," said the study"s co-senior author Xu Xun from BIG-Shenzhen, a genome sequencing center in China. "There"s still a chance that using this data with a large population size will help us to have a much broader vision of what the Chinese genetic population looks like."

NIPT, a test that sequences small amounts of a mother"s cell-free DNA to screen for fetal trisomy, has been growing in popularity in China. It has been administered to approximately 6 to 7 million Chinese women.

They found that the variation in a gene called NRG1 was linked to a greater or lesser incidence of twins. One variant of the gene is more common in mothers with twins and is associated with hyperthyroidism.

A variant of another gene, EMB, was associated with older first-time mothers, according to the study.

Also, the DNA sequencing in maternal blood revealed links between viruses and genes that determine susceptibility to disease. A variation in one gene was associated with a higher concentration of herpesvirus 6 in a mother"s blood.

Herpesvirus 6 is the most common cause of the relatively benign baby rash called roseola, but a high "viral load" correlates with more severe symptoms. People with Alzheimer"s disease also have higher levels of herpesvirus 6 in their brains.

"It"s amazing that this is even possible that you can take these massive samples and do association mapping to see what the genetic variants are that explain human traits," said co-author Rasmus Nielsen, a professor of integrative biology at the University of California, Berkeley, who oversaw the computational analysis performed by researchers at BGI in Shenzhen, China.

The study looked at 141,431 participants including 36 of China"s 55 ethnic minority groups.

"We"re excited about the volume: our participants represent 1/10,000 of the Chinese population, so it really is large sampling and a good reflection of the entire population," said co-senior author Jin Xin with BGI-Shenzhen and South China University of Technology.

This is a low-pass, rather than whole, genome sequencing but from many individuals which is cheaper to get but can still tell a lot, according to the researchers.

Their proof-of-concept analyses allowed scientists to identify patterns in the evolutionary history of China"s different ethnic groups, to pinpoint novel genetic loci linked to phenotypes like height and BMI, and to identify viral DNA distributions specific to the Chinese genome.

The researchers also found that many Chinese had genetic variants common among Indians, Southeast Asians and, along the route of the ancient Silk Road, Europeans.

Now, BIG-Shenzhen is analyzing the genomes of one million Chinese women who underwent non-invasive prenatal testing.


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